Ranibizumab and pegaptanib for the treatment of age-related macular degeneration: a systematic review and economic evaluation

Objectives: to assess the clinical effectiveness and cost-effectiveness of ranibizumab and pegaptanib for subfoveal choroidal neovascularisation (CNV) associated with wet age-related macular degeneration (AMD).Data sources: electronic databases were searched from inception to September 2006. Experts in the field were consulted and manufacturers’ submissions were examined.Review methods: the quality of included studies was assessed using standard methods and the clinical effectiveness data were synthesised through a narrative review with full tabulation of results. A model was developed to estimate the cost-effectiveness of ranibizumab and of pegaptanib (separately), compared with current practice or best supportive care, from the perspective of the NHS and Personal Social Services. Two time horizons were adopted for each model. The first adopted time horizons determined by the available trial data. The second analysis extrapolated effects of treatment beyond the clinical trials, adopting a time horizon of 10 years.Results: the combined analysis of two randomised controlled trials (RCTs) of pegaptanib [0.3 mg (licensed dose), 1.0 mg and 3.0 mg] versus sham injection in patients with all lesion types was reported by three publications (the VISION study). Three published RCTs of ranibizumab were identified (MARINA, ANCHOR, FOCUS), and an additional unpublished RCT was provided by the manufacturer (PIER). Significantly more patients lost less than 15 letters of visual acuity at 12 months when taking pegaptanib (0.3 mg: 70% of patients; 1.0 mg: 71% of patients; 3.0 mg: 65% of patients) or ranibizumab (0.3 mg: 94.3–94.5%; 0.5 mg: 94.6–96.4%) than sham injection patients (55% versus pegaptanib and 62.2% versus ranibizumab) or, in the case of ranibizumab, photodynamic therapy (PDT) (64.3%). The proportion of patients gaining 15 letters or more (a clinically important outcome having a significant impact on quality of life) was statistically significantly greater in the pegaptanib group for doses of 0.3 and 1.0 mg but not for 3.0 mg, and for all ranibizumab groups compared to the sham injection groups or PDT. This was also statistically significant for patients receiving 0.5 mg ranibizumab plus PDT compared with PDT plus sham injection. Pegaptanib patients lost statistically significantly fewer letters after 12 months of treatment than the sham group [mean letters lost: 7.5 (0.3 mg), 6.5 (1.0 mg) or 10 (3.0 mg) vs 14.5 (sham)]. In the MARINA and ANCHOR trials, ranibizumab patients gained letters of visual acuity at 12 months whereas patients with sham injection or PDT lost about 10 letters (p < 0.001) and in the PIER study, ranibizumab patients lost significantly fewer than the sham injection group. Significantly fewer patients receiving pegaptanib or ranibizumab deteriorated to legal blindness compared with the control groups. Adverse events were common for both pegaptanib and ranibizumab but most were mild to moderate. Drug costs for 1 year of treatment were estimated as £4626 for pegaptanib and £9134 for ranibizumab. Nondrug costs accounted for an additional £2614 for pegaptanib and £3120 for ranibizumab. Further costs are associated with the management of injectionrelated adverse events, from £1200 to £2100. For pegaptanib compared with usual care, the incremental cost-effectiveness ratio (ICER) ranged from £163,603 for the 2-year model to £30,986 for the 10-year model. Similarly, the ICERs for ranibizumab for patients with minimally classic and occult no classic lesions, compared with usual care, ranged from £152,464 for the 2-year model to £25,098 for the 10-year model.Conclusions: Patients with AMD of any lesion type benefit from treatment with pegaptanib or ranibizumab on measures of visual acuity when compared with sham injection and/or PDT. Patients who continuedtreatment with either drug appeared to maintain benefits after 2 years of follow-up. When comparing pegaptanib and ranibizumab, the evidence was less clear due to the lack of direct comparison through head-to-head trials and the lack of opportunity for indirect statistical comparison due to heterogeneity. The cost-effectiveness analysis showed that the two drugs offered additional benefit over the comparators of usual care and PDT but at increased cost. Future research should encompass trials to compare pegaptanib with ranibizumab and bevacizumab, and to investigate the role of verteporfin PDT in combination with these drugs. Studies are also needed to assess adverse events outside the proposed RCTs, to consider the optimal dosing regimes of these drugs and the benefits of re-treatment after initial treatment, and to review costing in more detail. Health state utilities and their relationship with visual acuity and contrast sensitivity, the relationship between duration of vision loss and the quality of life and functional impact of vision loss, behavioural studies of those genetically at risk are other topics requiring further research

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 referencesReview 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) ? 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 ? 40; BMI ? 30 and < 40 with Type 2 diabetes at baseline; and BMI ? 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 and £4000 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 ? 30 and < 40, ICERs were £18,930 at two years and £1397 at 20 years, and for BMI ? 30 and <35, ICERs were £60,754 at two years and £12,763 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 treatments for children with idiopathic steroid-resistant nephrotic syndrome: a systematic review

The clinical effectiveness literature on treatments for idiopathic SRNS in children is very limited. The available evidence suggests a beneficial effect of ciclosporin on remission rates and of cyclophosphamide on time to remission; however, the strength of the conclusions drawn is limited by the poor quality of the included studies. The other treatments included in this review were each evaluated by only one study, and none found a statistically significant effect. There is insufficient evidence to determine whether or not there is a clinically significant difference. The available data on costs and outcomes are sparse and do not permit the reliable modelling of the cost-effectiveness of treatments for SRNS at present. A modelling framework is suggested, should more relevant data become available. A well-designed adequately powered randomised controlled trial comparing ciclosporin with other treatments in children with SRNS without genetic mutation is require

Clinical and cost-effectiveness of once-daily versus more frequent use of same potency topical corticosteroids for atopic eczema: a systematic review and economic evaluation

OBJECTIVES: To assess the clinical and cost-effectiveness of once-daily use of topical corticosteroids versus more frequent use of same-potency topical corticosteroids in the treatment of people with atopic eczema. DATA SOURCES: Electronic databases. Bibliographies of included studies and related papers. Experts in the field. Manufacturer submissions to the National Institute for Clinical Excellence. REVIEW METHODS: Studies were assessed for inclusion according to predefined criteria by two reviewers. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Clinical effectiveness data were synthesised through a narrative review with full tabulation of results. RESULTS: One RCT comparing moderately potent corticosteroids, eight RCTs comparing potent corticosteroids and one RCT comparing very potent corticosteroids were included. No RCTs or CCTs of mild corticosteroids were eligible. Most RCTs were of poor methodological quality, although two were judged to be of good quality. The only study that compared moderately potent corticosteroids found no significant difference between once- and twice-daily application. For potent corticosteroids, some statistically significant differences in numbers of patients responding to treatment were identified favouring twice-daily treatment, but these were inconsistent between physician and patient assessment and outcomes selected for analysis. Two studies found a significant improvement in some symptoms with once-daily mometasone furoate compared with twice-daily application of a different active compound, while a third study found no significant differences. One good-quality study favoured twice-daily application of fluticasone propionate ointment, while other studies found no significant difference or an improvement in one symptom but not others. The only study comparing very potent corticosteroids found a statistically significant difference in comparative clinical response in favour of three-times daily treatment, but no difference in number of patients with at least a good response. There appears to be little difference in the frequency or severity of short-term events, however data are limited. No published economic evaluations were identified. Given findings on clinical effectiveness, where outcomes from the comparators are similar, the relative cost-effectiveness of once-daily versus more frequent application of topical corticosteroids becomes a case of cost-minimisation, where the least-cost alternative should be favoured, all else being equal. Topical corticosteroid products included in this review have a wide variation in price; the cost per 30 g/30 ml varies between GBP0.60 and GBP4.88. Specific decisions on the least-cost alternative, between once-daily and more frequent application of products, will be determined by the relative price of the products being compared. Where patients can be appropriately prescribed once-daily treatment of a similarly priced product, a reduction in the quantity of topical corticosteroid used will be expected. However, issues related to pack size for prescribed products and subsequent waste (unused product) could easily erode any potential saving. The potential cost-savings on prescribed products are very small at a patient level; although given the large numbers of patients with atopic eczema, cost savings in theory could be substantial. The presence of specifically marketed 'once-daily' topical corticosteroids, which are relatively expensive (per unit price), may result in additional costs should there be a general recommendation in favour of once-daily use of topical corticosteroids, compared to more frequent use. CONCLUSIONS: The literature is very limited; that available indicates the clinical effectiveness of once-daily and more frequent application of potent topical corticosteroids is very similar, but it does not offer a basis for favouring either option. The cost-effectiveness of once-daily versus more frequent use will depend on the generalisability of the findings to the specific treatment decision and the relative product prices. The trials included in this review generally refer to moderate to severe atopic eczema, whereas most patients have mild disease, and furthermore most of the included trials report on potent topical corticosteroids (eight of 10 RCTs); therefore the generalisability of the findings is limited. Further research is required on the clinical and cost-effectiveness of once-daily versus more frequent use of same potency corticosteroids, specifically on mild potency products for mild to moderate atopic eczema. Outcomes should include quality of life and compliance. [References: 79

The clinical and cost-effectiveness of bone anchored hearing aids (BAHAs) for people who are bilaterally deaf

Most people with hearing loss can benefit from conventional air-conduction hearing aids, however some people cannot wear these or do not benefit fully from them. A BAHA delivers sound through the skull by vibrations, missing out the outer and middle ears. Hearing loss can occur in both ears (bilateral). In these cases, BAHAs are usually fitted on just one side (unilaterally), but it has been suggested there may be benefits of bilateral BAHAs. The benefits and costs of bilateral compared with unilateral BAHAs and of BAHAs compared with conventional aids or surgery is not known.A systematic review and economic evaluation will be undertaken. Literature will be identified from several sources including electronic databases. Studies will be selected for inclusion using pre-defined and explicit criteria by two reviewers independently. Data will be extracted by two reviewers and the methodological quality of all studies will be assessed using recognised criteria. Data will be synthesised through a narrative review with tabulation of results of included studies. Where possible results will be synthesised through meta-analysis.We will develop an economic model either through adapting an existing model or developing our own new economic model to examine the costs and benefits of BAHAs within the UK. This will use data from our review of studies, advice from clinicians and patient representatives and data from recognised sources

Untold stories of living with a bariatric body: Long-term experiences of weight-loss surgery

This article explores patients' long‐term experiences after undergoing bariatric surgery (BS) by individual interviews and the interplay between biographical disruption and biographical flow when the body's normal physiology and anatomy are intentionally altered. Based on interpretative phenomenological analysis the findings show that the bariatric body is still prominent in daily life, positively by displacing the overweight body and negatively due to the development of unexpected health problems after surgery. Due to individual informed consent to the treatment, the negative consequences are perceived as self‐inflicted. The feelings of responsibility and shame make it difficult to seek help and to be open about undesirable long‐term effects and other health problems after surgery. The study argues that undergoing BS is a disruptive event with uncertain long‐term outcomes and living with a bariatric body as a vulnerable life continuously at the intersection of biographical disruption, flow and reinforcement. This study reinforces the importance of doing critical sociological studies of standardised medical interventions which aim to improve patients health problems. Included in these types of studies should be the patients' long‐term experiences and the awareness not to uncritically present their experiences as universal and the treatment result solely as the patients' own responsibility