Emma Loveman

The clinical effectiveness and cost-effectiveness of bariatric (weight loss) surgery for obesity: a systematic review and economic evaluation.

OBJECTIVES To assess the clinical effectiveness and cost-effectiveness of bariatric surgery for obesity. DATA SOURCES Seventeen electronic databases were searched [MEDLINE; EMBASE; PreMedline In-Process & Other Non-Indexed Citations; The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, DARE, NHS EED and HTA databases; Web of Knowledge Science Citation Index (SCI); Web of Knowledge ISI Proceedings; PsycInfo; CRD databases; BIOSIS; and databases listing ongoing clinical trials] from inception to August 2008. Bibliographies of related papers were assessed and experts were contacted to identify additional published and unpublished references. REVIEW METHODS Two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text using a standard form. Interventions investigated were open and laparoscopic bariatric surgical procedures in widespread current use compared with one another and with non-surgical interventions. Population comprised adult patients with body mass index (BMI) > or = 30 and young obese people. Main outcomes were at least one of the following after at least 12 months follow-up: measures of weight change; quality of life (QoL); perioperative and postoperative mortality and morbidity; change in obesity-related comorbidities; cost-effectiveness. Studies eligible for inclusion in the systematic review for comparisons of Surgery versus Surgery were RCTs. For comparisons of Surgery versus Non-surgical procedures eligible studies were RCTs, controlled clinical trials and prospective cohort studies (with a control cohort). Studies eligible for inclusion in the systematic review of cost-effectiveness were full cost-effectiveness analyses, cost-utility analyses, cost-benefit analyses and cost-consequence analyses. One reviewer performed data extraction, which was checked by two reviewers independently. Two reviewers independently applied quality assessment criteria and differences in opinion were resolved at each stage. Studies were synthesised through a narrative review with full tabulation of the results of all included studies. In the economic model the analysis was developed for three patient populations, those with BMI > or = 40; BMI > or = 30 and < 40 with Type 2 diabetes at baseline; and BMI > or = 30 and < 35. Models were applied with assumptions on costs and comorbidity. RESULTS A total of 5386 references were identified of which 26 were included in the clinical effectiveness review: three randomised controlled trials (RCTs) and three cohort studies compared surgery with non-surgical interventions and 20 RCTs compared different surgical procedures. Bariatric surgery was a more effective intervention for weight loss than non-surgical options. In one large cohort study weight loss was still apparent 10 years after surgery, whereas patients receiving conventional treatment had gained weight. Some measures of QoL improved after surgery, but not others. After surgery statistically fewer people had metabolic syndrome and there was higher remission of Type 2 diabetes than in non-surgical groups. In one large cohort study the incidence of three out of six comorbidities assessed 10 years after surgery was significantly reduced compared with conventional therapy. Gastric bypass (GBP) was more effective for weight loss than vertical banded gastroplasty (VBG) and adjustable gastric banding (AGB). Laparoscopic isolated sleeve gastrectomy (LISG) was more effective than AGB in one study. GBP and banded GBP led to similar weight loss and results for GBP versus LISG and VBG versus AGB were equivocal. All comparisons of open versus laparoscopic surgeries found similar weight losses in each group. Comorbidities after surgery improved in all groups, but with no significant differences between different surgical interventions. Adverse event reporting varied; mortality ranged from none to 10%. Adverse events from conventional therapy included intolerance to medication, acute cholecystitis and gastrointestinal problems. Major adverse events following surgery, some necessitating reoperation, included anastomosis leakage, pneumonia, pulmonary embolism, band slippage and band erosion. Bariatric surgery was cost-effective in comparison to non-surgical treatment in the reviewed published estimates of cost-effectiveness. However, these estimates are likely to be unreliable and not generalisable because of methodological shortcomings and the modelling assumptions made. Therefore a new economic model was developed. Surgical management was more costly than non-surgical management in each of the three patient populations analysed, but gave improved outcomes. For morbid obesity, incremental cost-effectiveness ratios (ICERs) (base case) ranged between 2000 pounds and 4000 pounds per QALY gained. They remained within the range regarded as cost-effective from an NHS decision-making perspective when assumptions for deterministic sensitivity analysis were changed. For BMI > or = 30 and 40, ICERs were 18,930 pounds at two years and 1397 pounds at 20 years, and for BMI > or = 30 and < 35, ICERs were 60,754 pounds at two years and 12,763 pounds at 20 years. Deterministic and probabilistic sensitivity analyses produced ICERs which were generally within the range considered cost-effective, particularly at the long twenty year time horizons, although for the BMI 30-35 group some ICERs were above the acceptable range. CONCLUSIONS Bariatric surgery appears to be a clinically effective and cost-effective intervention for moderately to severely obese people compared with non-surgical interventions. Uncertainties remain and further research is required to provide detailed data on patient QoL; impact of surgeon experience on outcome; late complications leading to reoperation; duration of comorbidity remission; resource use. Good-quality RCTs will provide evidence on bariatric surgery for young people and for adults with class I or class II obesity. New research must report on the resolution and/or development of comorbidities such as Type 2 diabetes and hypertension so that the potential benefits of early intervention can be assessed.

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

Infliximab for the treatment of adults with psoriasis.

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.

Modelling the Cost Effectiveness of Cholinesterase Inhibitors in the Management of Mild to Moderately Severe Alzheimer's Disease

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of infliximab for the treatment of moderate to severe plaque psoriasis, in accordance with the licensed indication, based on the evidence submission from Schering-Plough 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 severity [Psoriasis Area and Severity Index (PASI) score], remission rates, relapse rates and health-related quality of life. The main evidence in the submission comes from four randomised controlled trials (RCT) comparing infliximab with placebo and eight RCTs comparing either etanercept or efalizumab with placebo. At week 10, patients on infliximab had a significantly higher likelihood of attaining a reduction in PASI score than placebo patients. There were also statistically significant differences between infliximab and placebo in the secondary outcomes. In the comparator trials both the efalizumab and etanercept arms included a significantly higher proportion of patients who achieved a reduction in PASI score at week 12 than the placebo arms. No head-to-head studies were identified directly comparing infliximab with etanercept or efalizumab. The manufacturer carried out an indirect comparison, but the ERG had reservations about the comparison because of the lack of information presented and areas of uncertainty in relation to the included data. The economic model presented by the manufacturer was appropriate for the disease area and given the available data. The cost-effectiveness analysis estimates the mean length of time that an individual would respond to infliximab compared with continuous etanercept and the utility gains associated with this response. The base-case incremental cost-effectiveness ratio (ICER) for infliximab compared with continuous etanercept for patients with severe psoriasis was 26,095 pounds per quality-adjusted life-year. A one-way sensitivity analysis, a scenario analysis and a probabilistic sensitivity analysis were undertaken by the ERG. The ICER is highly sensitive to assumptions about the costs and frequency of inpatient stays for non-responders of infliximab. The guidance issued by NICE in August 2007 as a result of the STA states that infliximab within its licensed indication is recommended for the treatment of adults with very severe plaque psoriasis, or with psoriasis that has failed to respond to standard systematic therapies. Infliximab treatment should be continued beyond 10 weeks in people whose psoriasis has shown an adequate response to treatment within 10 weeks. In addition, when using the Dermatology Life Quality Index (DLQI), care should be taken to take into account the patients disabilities, to ensure DLQI continues to be an accurate measure.

Adalimumab for the treatment of psoriasis

AbstractObjective: To estimate the cost effectiveness (from the UK NHS and personal social services perspective) of the cholinesterase inhibitors donepezil, rivastigmine and galantamine compared with usual care in the treatment of mild to moderately severe Alzheimer’s disease. Patients had a mean age of 74 years, a mean disease duration of 1 year and a mean Alzheimer’s disease assessment scale-cognitive subscale score of 24. Methods: A pharmacoeconomic model was used to predict long-term outcomes over a 5-year time horizon and to estimate the cost effectiveness of cholinesterase inhibitors for the management of Alzheimer’s disease. The model structure is informed by a systematic review of the literature on the clinical and cost effectiveness of cholinesterase inhibitors and a review of the literature on the costs and outcomes associated with treatment for Alzheimer’s disease. The main outcome measure used was the cost per quality-adjusted life-year (QALY) gained. All healthcare costs (excluding cholinesterase inhibitor costs) were indexed to £ (2003 values). Drug costs are 2005 values. Multivariate probabilistic sensitivity analysis and scenario analysis were undertaken to assess uncertainty in the results. Results: The clinical benefits on cognition from treatment with cholinesterase inhibitors resulted in an incremental cost per QALY gained ranging from £53 780 to £74 735, over 5 years (vs usual care). Uncertainty analysis suggests that the probability of any of these treatments having an incremental cost per QALY of <£30 000 is <21%. The key determinants of cost effectiveness were the effectiveness of treatment, the mean treatment cost and the cost savings associated with an expected delay in disease progression. Conclusions: Results presented in this paper suggest that the use of cholinesterase inhibitors may not be a cost-effective use of NHS resources. Guidance from the National Institute for Health and Clinical Effectiveness (NICE) in the UK on their judgements surrounding the acceptability of technologies as an effective use of resources, indicates there would need to be special reasons for accepting cholinesterase inhibitors as a cost-effective use of NHS resources.

Ustekinumab for the treatment of moderate to severe psoriasis.

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of adalimumab for the treatment of moderate to severe plaque psoriasis based upon a review of the manufacturers submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submissions clinical evidence came from three randomised controlled trials comparing adalimumab with placebo, two extension studies and one ongoing open-label extension study. The studies were of reasonable quality and measured a range of clinically relevant outcomes. A higher proportion of patients on 40 mg adalimumab every other week achieved an improvement on the Psoriasis Area and Severity Index (PASI) of at least 75% (PASI 75) compared with placebo groups after 12 or 16 weeks of treatment, and there was a statistically significant difference in favour of adalimumab for the proportion of patients achieving a PASI 50 and a PASI 90. In a mixed treatment comparison, for each PASI outcome the probability of a response was greater for infliximab than for adalimumab, but the probability of response with adalimumab was greater than that with etanercept, efalizumab and non-biological systemic therapies. Adverse event rates were similar in the treatment and placebo arms and discontinuations because of adverse events were low and comparable between groups. The submissions economic model presents treatment effectiveness for adalimumab versus other biological therapies based upon utility values obtained from two clinical trials. The model is generally internally consistent and appropriate to psoriasis in terms of structural assumptions and the methods used are appropriate. The base-case incremental cost-effectiveness ratio for adalimumab compared with supportive care for patients with severe psoriasis was 30,538 pounds per quality-adjusted life-year. Scenario analysis shows that the model was most sensitive to the utility values used. Weaknesses of the clinical evidence included not undertaking a systematic review of the comparator trials, providing very little in the way of a narrative synthesis of outcome data from the key trials and not performing a meta-analysis so that the overall treatment effect of adalimumab achieved across the trials is unknown. Weaknesses of the economic model included that the assumptions made to estimate the cost-effectiveness of intermittent etanercept used inconsistent methodology for costs and benefits and there were no clear data on the amount of inpatient care required under supportive care. The NICE guidance issued as a result of the STA states that adalimumab is recommended as a treatment option for adults with plaque psoriasis in whom anti-tumour necrosis factor treatment is being considered and when the disease is severe and when the psoriasis has not responded to standard systemic therapies or the person is intolerant to or has a contraindication to these treatments.

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.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of ustekinumab for the treatment of moderate to severe psoriasis based upon a review of the manufacturers submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submissions main evidence came from three randomised controlled trials (RCTs), of reasonable methodological quality and measuring a range of clinically relevant outcomes. Higher proportions of participants treated with ustekinumab (45 mg and 90 mg) than with placebo or etanercept achieved an improvement on the Psoriasis Area and Severity Index (PASI) of at least 75% (PASI 75) after 12 weeks. There were also statistically significant differences in favour of ustekinumab over placebo for PASI 50 and PASI 90 results, and for ustekinumab over etanercept for PASI 90 results. A weight-based subgroup dosing analysis for each trial was presented, but the methodology was poorly described and no statistical analysis to support the chosen weight threshold was presented. The manufacturer carried out a mixed treatment comparison (MTC); however, the appropriateness of some of the methodological aspects of the MTC is uncertain. The incidence of adverse events was similar between groups at 12 weeks and withdrawals due to adverse events were low and less frequent in the ustekinumab than in the placebo or etanercept groups; however, statistical comparisons were not reported. The manufacturers economic model of treatments for psoriasis compared ustekinumab with other biological therapies. The model used a reasonable approach; however, it is not clear whether the clinical effectiveness estimates from the subgroup analysis, used in the base-case analysis, were methodologically appropriate. The base-case incremental cost-effectiveness ratio for ustekinumab versus supportive care was 29,587 pounds per quality-adjusted life-year (QALY). In one-way sensitivity analysis the model was most sensitive to the number of hospital days associated with supportive care, the cost estimate for intermittent etanercept 25 mg and the utility scores used. In the ERGs scenario analysis the model was most sensitive to the price of ustekinumab 90 mg, the proportion of patients with baseline weight > 100 kg and the relative risk of intermittent versus continuous etanercept 25 mg. In the ERGs probabilistic sensitivity analysis ustekinumab had the highest probability of being cost-effective at conventional NICE thresholds, assuming the same price for the 45-mg and 90-mg doses; however, doubling the price of ustekinumab 90 mg resulted in ustekinumab no longer dominating the comparators. In conclusion, the clinical effectiveness and cost-effectiveness of ustekinumab in relation to other drugs in this class is uncertain. Provisional NICE guidance issued as a result of the STA states that ustekinumab is recommended as a treatment option for adults with plaque psoriasis when a number of criteria are met. Final guidance is anticipated in September 2009.

Comparing new treatments for idiopathic pulmonary fibrosis – a network meta-analysis

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

BackgroundThe treatment landscape for idiopathic pulmonary fibrosis, a devastating lung disease, is changing. To investigate the effectiveness of treatments for idiopathic pulmonary fibrosis we undertook a systematic review, network meta-analysis and indirect comparison.MethodsWe searched MEDLINE, EMBASE and The Cochrane library for relevant studies. Randomised controlled trials of pirfenidone, nintedanib or N-acetylcysteine were eligible. Predefined processes for selecting references, extracting data and assessing study quality were applied. Our network meta-analysis of published data used a fixed effect model. For forced vital capacity measures a standardised mean difference approach was used and converted to odds ratios for interpretation.ResultsOf 1076 references, 67 were retrieved and 11 studies included. Studies were of reasonable size, populations were similar, and the overall quality was good. Only two treatments, pirfenidone (odds ratio 0.62, 95% credible interval 0.52, 0.74) and nintedanib (0.41, 95% credible interval 0.34, 0.51) produced a statistically significant slowing in the rate of forced vital capacity decline compared with placebo. In an indirect comparison, results indicate that nintedanib is statistically significantly better than pirfenidone in slowing forced vital capacity decline (odds ratio 0.67, 95% credible interval 0.51, 0.88). Results were stable in scenario analysis and random effects models. Indirect comparisons of mortality were not statistically significant between nintedanib and pirfenidone.ConclusionsTwo treatments show beneficial effects and when compared indirectly nintedanib appears to have superior benefit on forced vital capacity. Limitations to indirect comparisons should be considered when interpreting these results, however, our findings can be useful to inform treatment decisions.

The effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: systematic review, network meta-analysis and health 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