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ABSTRACT: Women in England (aged 25-64 years) are invited for cervical screening every 3-5 years to assess for cervical intraepithelial neoplasia (CIN) or cancer. CIN is a term describing abnormal changes in the cells of the cervix, ranging from CIN1 to CIN3, which is precancerous. Colposcopy is used to visualise the cervix. Three adjunctive colposcopy technologies for examination of the cervix have been included in this assessment: Dynamic Spectral Imaging System (DySIS), the LuViva Advanced Cervical Scan and the Niris Imaging System.
To determine the clinical effectiveness and cost-effectiveness of adjunctive colposcopy technologies for examination of the uterine cervix for patients referred for colposcopy through the NHS Cervical Screening Programme.
Sixteen electronic databases [Allied and Complementary Medicine Database (AMED), BIOSIS Previews, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Database of Abstracts of Reviews of Effects (DARE), EMBASE, Health Management Information Consortium (HMIC), Health Technology Assessment (HTA) database; Inspec, Inside Conferences, MEDLINE, NHS Economic Evaluation Database (NHS EED), PASCAL, Science Citation Index Expanded (SCIE) and Science Citation Index (SCI) - Conference Proceedings], and two clinical trial registries [ClinicalTrials.gov and Current Controlled Trials (CCT)] were searched to September-October 2011.
Studies comparing DySIS, LuViva or Niris with conventional colposcopy were sought; a narrative synthesis was undertaken. A decision-analytic model was developed, which measured outcomes in terms of quality-adjusted life-years (QALYs) and costs were evaluated from the perspective of the NHS and Personal Social Services with a time horizon of 50 years.
Six studies were included: two studies of DySIS, one study of LuViva and three studies of Niris. The DySIS studies were well reported and had a low risk of bias; they found higher sensitivity with DySIS (both the DySISmap alone and in combination with colposcopy) than colposcopy alone for identifying CIN2+ disease, although specificity was lower with DySIS. The studies of LuViva and Niris were poorly reported and had limitations, which indicated that their results were subject to a high risk of bias; the results of these studies cannot be considered reliable. The base-case cost-effectiveness analysis suggests that both DySIS treatment options are less costly and more effective than colposcopy alone in the overall weighted population; these results were robust to the ranges tested in the sensitivity analysis. DySISmap alone was more costly and more effective in several of the referral groups but the incremental cost-effectiveness ratio (ICER) was never higher than £1687 per QALY. DySIS plus colposcopy was less costly and more effective in all reasons for referral. Only indicative analyses were carried out on Niris and LuViva and no conclusions could be made on their cost-effectiveness.
The assessment is limited by the available evidence on the new technologies, natural history of the disease area and current treatment patterns.
DySIS, particularly in combination with colposcopy, has higher sensitivity than colposcopy alone. There is no reliable evidence on the clinical effectiveness of LuViva and Niris. DySIS plus colposcopy appears to be less costly and more effective than both the DySISmap alone and colposcopy alone; these results were robust to the sensitivity analyses undertaken. Given the lack of reliable evidence on LuViva and Niris, no conclusions on their potential cost-effectiveness can be drawn. There is some uncertainty about how generalisable these findings will be to the population of women referred for colposcopy in the future, owing to the introduction of the human papillomavirus (HPV) triage test and uptake of the HPV vaccine.
PROSPERO Record CRD42011001614.
The National Institute for Health Research Health Technology Assessment programme.
Health technology assessment (Winchester, England). 03/2013; 17(8):1-240.
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ABSTRACT: EOS is a biplane X-ray imaging system manufactured by EOS Imaging (formerly Biospace Med, Paris, France). It uses slot-scanning technology to produce a high-quality image with less irradiation than standard imaging techniques.
To determine the clinical effectiveness and cost-effectiveness of EOS two-dimensional (2D)/three-dimensional (3D) X-ray imaging system for the evaluation and monitoring of scoliosis and other relevant orthopaedic conditions.
For the systematic review of EOS, electronic databases (MEDLINE, Allied and Complementary Medicine Database, BIOSIS Previews, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, EMBASE, Health Management Information Consortium, Inspec, ISI Science Citation Index and PASCAL), clinical trials registries and the manufacturer's website were searched from 1993 to November 2010.
A systematic review of studies comparing EOS with standard X-ray [film, computed radiography (CR) or digital radiography] in any orthopaedic condition was performed. A narrative synthesis was undertaken. A decision-analytic model was developed to assess the cost-effectiveness of EOS in the relevant indications compared with standard X-ray and incorporated the clinical effectiveness of EOS and the adverse effects of radiation. The model incorporated a lifetime horizon to estimate outcomes in terms of quality-adjusted life-years (QALYs) and costs from the perspective of the NHS.
Three studies met the inclusion criteria for the review. Two studies compared EOS with film X-ray and one study compared EOS with CR. The three included studies were small and of limited quality. One study used an earlier version of the technology, the Charpak system. Both studies comparing EOS with film X-ray found image quality to be comparable or better with EOS overall. Radiation dose was considerably lower with EOS: ratio of means for posteroanterior spine was 5.2 (13.1 for the study using the Charpak system); ratio of means for the lateral spine was 6.2 (15.1 for the study using the Charpak system). The study comparing EOS with CR found image quality to be comparable or better with EOS. Radiation dose was considerably lower with EOS than CR; ratio of means for the centre of the back was 5.9 and for the proximal lateral point 8.8. The lowest ratio of means was at the nape of the neck, which was 2.9. No other outcomes were assessed in the included studies, such as implications for patient management from the nature and quality of the image. Patient throughput is the major determinant of the cost-effectiveness of EOS. The average cost per procedure of EOS decreases with utilisation. Using estimates of patient throughput at national level from Hospital Episode Statistics data suggests that EOS is not cost-effective for the indications considered. Throughput in the region of 15,100 to 26,500 (corresponding to a workload of 60 to 106 patient appointments per working day) for EOS compared with a throughput of only 7530 for CR (30 patient appointments per working day) is needed to achieve an incremental cost-effectiveness ratio of £30,000 per QALY. EOS can be shown to be cost-effective only when compared with CR if the utilisation for EOS is about double the utilisation of CR.
The main limitation of the systematic review of the clinical effectiveness of EOS was the limited number and quality of the data available. In particular, there were no studies assessing the potential health benefits arising from the quality and nature of the image, over and above those associated with reduced radiation exposure. Uncertainty in the model inputs was not fully explored owing to a lack of reporting of standard deviations or confidence intervals in the published literature for most of the parameters. As a result, uncertainty in the cost-effectiveness results was not presented.
Radiation dose is considerably lower with EOS than standard X-ray, whereas image quality remains comparable or better with EOS. However, the long-term health benefits from reduced radiation exposure with EOS are very small and there was a lack of data on other potential patient health benefits. The implications of any changes in the quality and nature of the EOS image compared with standard X-ray, for patient health outcomes, needs to be assessed. Given the higher cost of an EOS machine, utilisation is the major determinant of cost-effectiveness. Estimates of patient throughput at national level suggest that EOS is not cost-effective.
The National Institute for Health Research Health Technology Assessment programme.
Health technology assessment (Winchester, England). 03/2012; 16(14):1-188.
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ABSTRACT: This paper presents a summary of the evidence review group (ERG) report into the use of golimumab for the treatment of psoriatic arthritis (PsA). The main clinical effectiveness data were derived from a single phase III randomised controlled trial (RCT: GO-REVEAL) that compared golimumab with placebo for treating patients with active and progressive PsA who were symptomatic despite the use of previous disease-modifying antirheumatic drugs or non-steroidal anti-inflammatory drugs. The 14-week data showed that, compared with placebo, golimumab 50 mg significantly improved joint disease response as measured by American College of Rheumatology (ACR) 20 [relative risk (RR) 5.73, 95% confidence interval (CI) 3.24 to 10.56] and Psoriatic Arthritis Response Criteria (PsARC) (RR 3.45, 95% CI 2.49 to 4.87), and skin disease response as measured by the Psoriasis Area and Severity Index (PASI) 75 (RR 15.95, 95% CI 4.62 to 59.11). The 24-week absolute data showed that these treatment benefits were maintained. There was a significant improvement in patients' functional status as measured by the Health Assessment Questionnaire (HAQ) change from baseline at 24 weeks (-0.33, p < 0.001). The open-label extension data showed that these beneficial effects were also maintained at 52 and 104 weeks. However, PASI 50 and PASI 90 at 14 weeks, and all of the PASI outcomes at 24 weeks, were not performed on the basis of intention-to-treat analysis. Furthermore, analyses of the 24-week data were less robust, failing to adjust for treatment contamination due to patient crossover at week 16. The manufacturer conducted a mixed treatment comparison (MTC) analysis. The ERG considered the assumption of exchangeability between the trials for the purpose of the MTC analysis to be acceptable, and the statistical approach in the MTC analysis to be reliable. Regarding the safety evaluation of golimumab, the manufacturer failed to provide longer-term data or to consider adverse event data of golimumab from controlled studies in other conditions, such as rheumatoid arthritis and ankylosing spondylitis. Although the adverse effect profile of golimumab appears similar to other anti-tumour necrosis factor (TNF) agents, the longer-term safety profile of golimumab remains uncertain. The manufacturer's submission presented a decision model to compare etanercept, infliximab, golimumab and adalimumab versus palliative care for patients with PsA. In the base-case model, 73% of the cohort of patients were assumed to have significant psoriasis (> 3% of body surface area). Estimates of the effectiveness of anti-TNF agents in terms of PsARC, HAQ change and PASI change were obtained from an MTC analysis of RCT data. The manufacturer failed to calculate incremental cost-effectiveness ratios (ICERs) correctly by comparing golimumab with palliative care instead of the most cost-effective alternative (etanercept). Despite the manufacturer's claim that golimumab is a cost-effective treatment option, the manufacturer's own model showed that golimumab is not cost-effective compared with other biologics when the ICERs are correctly calculated. None of the sensitivity analyses carried out by the manufacturer or the ERG regarding uncertainty in the estimates of clinical effectiveness, the acquisition and administration cost of drugs, the cost of treating psoriasis and the utility functions estimated to generate health outcomes changed this conclusion. However, a key area in determining the cost-effectiveness of anti-TNF agents is whether they should be treated as a class. If all anti-TNF agents are considered equally effective then etanercept, adalimumab and golimumab have very nearly equal costs and equal quality-adjusted life-years (QALYs), and all have an ICER of about £ 15,000 per QALY versus palliative care, whereas infliximab with a higher acquisition cost is dominated by the other biologics.
Health technology assessment (Winchester, England). 05/2011; 15 Suppl 1:87-95.
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M Rodgers,
D Epstein,
L Bojke,
H Yang,
D Craig,
T Fonseca,
L Myers,
I Bruce,
R Chalmers,
S Bujkiewicz,
M Lai,
N Cooper,
K Abrams,
D Spiegelhalter,
A Sutton, M Sculpher,
N Woolacott
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ABSTRACT: Etanercept, infliximab and adalimumab are licensed in the UK for the treatment of active and progressive psoriatic arthritis (PsA) in adults who have an inadequate response to standard treatment.
To determine the clinical effectiveness, safety and cost-effectiveness of these biologic agents in the treatment of active and progressive PsA.
Systematic reviews were performed, with data sought from 10 electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, Conference Proceedings Citation Index - Science, ClinicalTrials.gov, metaRegister of Current Controlled Trials, NHS Economic Evaluation Database, Health Economic Evaluations Database and EconLit) up to June 2009.
Full paper manuscripts of titles/abstracts considered relevant were obtained and assessed for inclusion by two reviewers according to criteria on study design, interventions, participants and outcomes. Data on study and participant characteristics, efficacy outcomes, adverse effects, costs to the health service and cost-effectiveness were extracted, along with baseline data where reported. The primary efficacy outcomes were measures of anti-inflammatory response, skin lesion response and functional status, and the safety outcome was the incidence of serious adverse events. The primary measure of cost-effectiveness was incremental cost per additional quality-adjusted life-year (QALY). Standard meta-analytic techniques were applied to efficacy data. Published cost-effectiveness studies and the economic analyses submitted to the National Institute for Health and Clinical Excellence (NICE) by the biologic manufacturers were reviewed. An economic model was developed by updating the model produced by the York Assessment Group for the previous NICE appraisal of biologics in PsA.
Pooled estimates of effect demonstrated a significant improvement in patients with PsA for all joint disease and functional status outcomes at 12-14 weeks' follow-up. The biologic treatment significantly reduced joint symptoms for etanercept [relative risk (RR) 2.60, 95% confidence interval (CI) 1.96 to 3.45], infliximab (RR 3.44, 95% CI 2.53 to 4.69) and adalimumab (RR 2.24, 95% CI 1.74 to 2.88), with 24-week data demonstrating maintained treatment effects. Trial data demonstrated a significant effect of all three biologics on skin disease at 12 or 24 weeks. Evidence synthesis found that infliximab appeared to be most effective across all outcomes of joint and skin disease. The response in joint disease was greater with etanercept than with adalimumab, whereas the response in skin disease was greater with adalimumab than with etanercept, although these differences are not statistically significant. Under base-case assumptions, etanercept was the most likely cost-effective strategy for patients with PsA and mild-to-moderate psoriasis if the threshold for cost-effectiveness was £20,000 or £30,000 per QALY. All biologics had a similar probability of being cost-effective for patients with PsA and moderate-to-severe psoriasis at a threshold of £20,000 per QALY.
Limited available efficacy data and difficulty in assessing PsA activity and its response to biologic therapy.
The data indicated that etanercept, infliximab and adalimumab were efficacious in the treatment of PsA compared with placebo, with beneficial effects on joint symptoms, functional status and skin. Short-term data suggested that these biologic agents can delay joint disease progression and evidence to support their use in the treatment of PsA is convincing. Future research would benefit from long-term observational studies with large sample sizes of patients with PsA to demonstrate that beneficial effects are maintained, along with further monitoring of the safety profiles of the biologic agents.
The National Institute for Health Research Health Technology Assessment programme.
Health technology assessment (Winchester, England). 02/2011; 15(10):i-xxi, 1-329.
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ABSTRACT: This paper presents a summary of the evidence review group (ERG) report into capecitabine for advanced gastric cancer (aGC). Capecitabine is an oral prodrug of 5-fluorouracil (5-FU). The decision problem addressed was the use of capecitabine (X) compared to 5-FU (F), in combination regimens with platinum agents [cisplatin (C) or oxaliplatin (O)] with or without epirubicin (E), in patients with inoperable aGC. Approximately 7000 new cases of gastric cancer are diagnosed in England and Wales every year. Of these, 80% are candidates for palliative chemotherapy and around 2900 receive such treatment. The standard UK practice for patients with aGC who are considered fit enough has consisted of a triplet regimen comprising intravenous 5-FU in combination with a platinum agent (capecitabine or oxaliplatin) and epirubicin. The manufacturer's submission (MS) focused on direct evidence from two phase III non-inferiority randomised controlled trials (RCTs), REAL-2 (Randomized ECF for Advanced and Locally advanced oesophagogastric cancer-2; n = 1002) and ML17032 (n = 316). REAL-2 randomised patients to four regimens (ECF, ECX, EOF and EOX) to compare 5-FU with capecitabine and cisplatin with oxaliplatin, whereas ML17032 compared CX with CF. Efficacy outcomes from these trials were pooled in an individual patient data (IPD) meta-analysis. Both RCTs demonstrated statistically significant non-inferiority of capecitabine on the outcome of overall survival (OS) assessed in the per-protocol population; equivalent results were also demonstrated for progression-free survival (PFS). The IPD meta-analysis found a statistically significant benefit in OS for capecitabine compared with 5-FU [unadjusted hazard ratio (HR): 0.87; 95% confidence interval (CI) 0.77 to 0.98, p = 0.027]. There was no evidence of a poorer safety profile for capecitabine overall, nor of any difference in quality of life (QoL) between the two fluoropyrimidines. The MS included a de novo economic evaluation based on a cost-minimisation analysis (CMA), where the costs of capecitabine-based regimens were compared with their equivalent 5-FU-based regimens in aGC. A time horizon of 5.5 cycles (each lasting for 21 days) was used in the base-case analysis, representing the duration of treatment. The results of the manufacturer's base-case analysis showed that capecitabine regimens are associated with mean net cost savings of 1620 pounds (ECX vs ECF), 1572 pounds (EOX vs EOF) and 4210 pounds (CX vs CF). The manufacturer failed to comment explicitly on the uncertainty around the estimates of efficacy and on the fact that the IPD meta-analysis suggests that capecitabine may actually be more effective on average. Further analyses exploring additional costs incurred by the UK NHS from extending survival duration showed that these are unlikely to have a material effect on conclusions. A full probabilistic analysis was not performed; however, the evidence explored by the MS and ERG is consistent in suggesting that capecitabine has a lower mean cost than 5-FU-based regimens. The submission was considered to contain convincing evidence of the non-inferiority of capecitabine to 5-FU on survival; this evidence was considered to be applicable to UK practice. Although some uncertainty remains, the ERG deemed CMA to be an appropriate framework with which to analyse this decision problem. Overall cost estimates for the CMA were generated appropriately and were robust to uncertainties regarding assumptions and sources. At the time of writing, the guidance document issued by NICE on 28 July 2010 states that capecitabine in combination with a platinum-based regimen is recommended for the first-line treatment of inoperable advanced gastric cancer.
Health technology assessment (Winchester, England). 10/2010; 14(Suppl. 2):11-7.
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ABSTRACT: The cost-effectiveness of sugammadex for the routine reversal of muscle relaxation produced by rocuronium or vecuronium in UK practice is uncertain. We performed a systematic review of randomized controlled trials of sugammadex compared with neostigmine/glycopyrrolate and an economic assessment of sugammadex for the reversal of moderate or profound neuromuscular block (NMB) produced by rocuronium or vecuronium. The economic assessment aimed to establish the reduction in recovery time and the 'value of time saved' which would be necessary for sugammadex to be potentially cost-effective compared with existing practice. Three trials indicated that sugammadex 2 mg kg⁻¹ (4 mg kg⁻¹) produces more rapid recovery from moderate (profound) NMB than neostigmine/glycopyrrolate. The economic assessment indicated that if the reductions in recovery time associated with sugammadex in the trials are replicated in routine practice, sugammadex would be cost-effective if those reductions are achieved in the operating theatre (assumed value of staff time, £4.44 per minute), but not if they are achieved in the recovery room (assumed value of staff time, £0.33 per minute). However, there is considerable uncertainty in these results. Sugammadex has the potential to be cost-effective compared with neostigmine/glycopyrrolate for the reversal of rocuronium-induced moderate or profound NMB, provided that the time savings observed in trials can be achieved and put to productive use in clinical practice. Further research is required to evaluate the effects of sugammadex on patient safety, predictability of recovery from NMB, patient outcomes, and efficient use of resources.
BJA British Journal of Anaesthesia 10/2010; 105(5):558-67. · 4.24 Impact Factor
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ABSTRACT: Sugammadex 16 mg kg⁻¹ can be used for the immediate reversal of neuromuscular block 3 min after administration of rocuronium and could be used in place of succinylcholine for emergency intubation. We have systematically reviewed the efficacy and cost-effectiveness and made an economic assessment of sugammadex for immediate reversal. The economic assessment investigated whether sugammadex appears cost-effective under various assumptions about the value of any reduction in recovery time with sugammadex, the likelihood of a 'can't intubate, can't ventilate' (CICV) event, the age of the patient, and the length of the procedure. Three trials were included in the efficacy review. Sugammadex administered 3 or 5 min after rocuronium produced markedly faster recovery than placebo or spontaneous recovery from succinylcholine-induced block. No published economic evaluations were found. Our economic analyses showed that sugammadex appears more cost-effective, where the value of any reduction in recovery time is greater, where the reduction in mortality compared with succinylcholine is greater, and where the patient is younger, for lower probabilities of a CICV event and for long procedures which do not require profound block throughout. Because of the lack of evidence, the value of some parameters remains unknown, which makes it difficult to provide a definitive assessment of the cost-effectiveness of sugammadex in practice. The use of sugammadex in combination with high-dose rocuronium is efficacious. Further research is needed to clarify key parameters in the analysis and to allow a fuller economic assessment.
BJA British Journal of Anaesthesia 10/2010; 105(5):568-75. · 4.24 Impact Factor
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ABSTRACT: Sugammadex (Bridion) is a newly developed agent for the reversal of neuromuscular blockade (NMB) induced by rocuronium or vecuronium. Sugammadex can reverse profound blockade and can be given for immediate reversal and its use would avoid the potentially serious adverse effects of the currently used agent, succinylcholine. Also, sugammadex can reverse NMB more quickly and predictably than existing agents.
To determine the clinical effectiveness and cost-effectiveness of sugammadex for the reversal of muscle relaxation after general anaesthesia in UK practice following routine or rapid induction of NMB.
Medical databases [including MEDLINE, EMBASE, CINAHL, Science Citation Index, BIOSIS and Cochrane Central Register of Controlled Trials (CENTRAL), conference proceedings, internet sites and clinical trials registers] were searched to identify published and unpublished studies. The main searches were carried out in May 2008 and supplemented by current awareness updates up until November 2008.
For the clinical effectiveness review, randomised controlled trials of sugammadex against placebo or an active comparator (neostigmine + glycopyrrolate) for the reversal of moderate or profound NMB and for immediate reversal (spontaneous recovery from succinylcholine-induced blockade) were included. The primary effectiveness outcome was speed of recovery from NMB, as measured by objective monitoring of neuromuscular function. For the cost-effectiveness review, a de novo economic assessment considered the routine induction of NMB and the rapid induction and/or reversal of NMB, and threshold analyses were carried out on a series of pairwise comparisons to establish how effective sugammadex needs to be to justify its cost.
The review of clinical effectiveness included four randomised active-control trials of sugammadex, nine randomised placebo-controlled trials and five studies in special populations. A total of 2132 titles and abstracts and 265 full-text publications were screened. The included trials indicated that sugammadex produces more rapid recovery from moderate or profound NMB than placebo or neostigmine. Median time to recovery from moderate blockade was 1.3-1.7 minutes for rocuronium + sugammadex, 21-86 minutes for rocuronium + placebo and 17.6 minutes for rocuronium + neostigmine. In profound blockade, median time to recovery was 2.7 minutes for rocuronium + sugammadex, 30 to > 90 minutes for rocuronium + placebo, and 49 minutes for rocuronium + neostigmine. Results for vecuronium were similar. In addition, recovery from NMB was faster with rocuronium reversed by sugammadex 16 mg/kg after 3 minutes (immediate reversal) than with succinylcholine followed by spontaneous recovery (median time to primary outcome 4.2 versus 7.1 minutes). The evidence base for modelling cost-effectiveness is very limited. However, assuming that the reductions in recovery times seen in the trials can be achieved in routine practice and can be used productively, sugammadex [2 mg/kg (4 mg/kg)] is potentially cost-effective at its current list price for the routine reversal of rocuronium-induced moderate (profound) blockade, if each minute of recovery time saved can be valued at approximately 2.40 pounds (1.75 pounds) or more. This is more likely to be achieved if any reductions in recovery time are in the operating room (estimated value of 4.44 pounds per minute saved) rather than the recovery room (estimated value of 0.33 pounds per minute saved). The results were broadly similar for rocuronium- and vecuronium-induced blockade. For rapid reversal of NMB it appeared that any reduction in morbidity from adopting sugammadex is unlikely to result in significant cost savings.
The evidence base was not large and many of the published trials were dose-finding and safety studies with very small sample sizes. Also, some relevant outcomes, in particular patient experience/quality of life and resources/costs used, were either not investigated or not reported. In addition, it is likely that the patients included in the efficacy trials were relatively young and in good general health compared with the overall surgical population. Regarding the economic evaluation, there appears to be no evidence linking measures of clinical efficacy to patients' health-related quality of life and mortality risks.
Sugammadex may be a cost-effective option compared with neostigmine + glycopyrrolate for reversal of moderate NMB and also provides the facility to recover patients from profound blockade. Rocuronium + sugammadex could be considered as a replacement for succinylcholine for rapid induction (and reversal) of NMB, although this may not be a cost-effective option in some types of patient at current list prices for sugammadex. Considerable uncertainties remain about whether the full benefits of sugammadex can be realised in clinical practice.
Health technology assessment (Winchester, England). 07/2010; 14(39):1-211.
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ABSTRACT: This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of alitretinoin for the treatment of adults with severe chronic hand eczema refractory to topical steroid treatment in accordance with the licensed indication, based upon the evidence submission from Basilea Pharmaceuticals Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The clinical evidence came from a single placebo-controlled randomised controlled trial of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe chronic hand eczema (CHE) unresponsive to topical steroids. A statistically significantly greater proportion of patients using alitretinoin achieved the primary end point of clear or almost clear hands by week 24 than did those with placebo. Dose-dependent headache was the most commonly reported adverse event in patients treated with alitretinoin. Serious adverse events were rare, but alitretinoin was associated with increases in both total cholesterol and triglycerides, which has implications for risks of future cardiovascular events. The manufacturer submitted a de novo decision analytic model to estimate, over a time horizon of 3 years, the cost-effectiveness of alitretinoin versus the other relevant comparators identified by NICE. In response to the points of clarification put to it by the ERG regarding the initial submission, the manufacturer provided additional evidence and a revised decision analytic model with a 'placebo' arm. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were 8614 pounds per quality-adjusted life-year (QALY) versus ciclosporin, -469 pounds per QALY versus psoralen + UVA (with alitretinoin dominant) and 10,612 pounds per QALY versus azathioprine. These ICERs decreased as the time horizon was extended in sensitivity analyses. In patients with hyperkeratotic CHE and in women of child-bearing potential, the ICER remained below 20,000. pounds When the health-related quality of life (HRQoL) values used in the model were replaced with those derived from an alternative study, these ICERs increased significantly (to 22,312 pounds per QALY for alitretinoin versus azathioprine). In the revised model, alitretinoin was reported to have an ICER of 12,931 pounds per QALY gained versus supportive care (placebo). However, the model underestimates the costs of treatment associated with alitretinoin. The manufacturer assumed that patients receiving alitretinoin visited the dermatologist every 4 weeks and ceased treatment as soon as they responded to it. If, in practice, patients would receive treatment for longer than this, then the manufacturer's model will have significantly underestimated the costs to the NHS. Additional analyses undertaken by the ERG produced ICERs close to 30,000 pounds per QALY gained for alitretinoin versus supportive care. This was largely due to uncertainty surrounding the impact of alitretinoin on HRQoL. The placebo-controlled trials conducted to date have established that alitretinoin can be efficacious for the treatment of severe CHE refractory to topical steroids, but longer term follow-up of trials or the implementation of registries is required to better establish the longer term efficacy or safety of alitretinoin. NICE recommended the use of alitretinoin for patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. Treatment was recommended to be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.
Health technology assessment (Winchester, England). 05/2010; 14 Suppl 1:39-46.
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H Hemingway,
M Henriksson,
R Chen,
J Damant,
N Fitzpatrick,
K Abrams,
A Hingorani,
M Janzon,
M Shipley,
G Feder,
B Keogh,
U Stenestrand,
K McAllister,
J-C Kaski,
A Timmis,
S Palmer, M Sculpher
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ABSTRACT: To determine the effectiveness and cost-effectiveness of a range of strategies based on conventional clinical information and novel circulating biomarkers for prioritising patients with stable angina awaiting coronary artery bypass grafting (CABG).
MEDLINE and EMBASE were searched from 1966 until 30 November 2008.
We carried out systematic reviews and meta-analyses of literature-based estimates of the prognostic effects of circulating biomarkers in stable coronary disease. We assessed five routinely measured biomarkers and the eight emerging (i.e. not currently routinely measured) biomarkers recommended by the European Society of Cardiology Angina guidelines. The cost-effectiveness of prioritising patients on the waiting list for CABG using circulating biomarkers was compared against a range of alternative formal approaches to prioritisation as well as no formal prioritisation. A decision-analytic model was developed to synthesise data on a range of effectiveness, resource use and value parameters necessary to determine cost-effectiveness. A total of seven strategies was evaluated in the final model.
We included 390 reports of biomarker effects in our review. The quality of individual study reports was variable, with evidence of small study (publication) bias and incomplete adjustment for simple clinical information such as age, sex, smoking, diabetes and obesity. The risk of cardiovascular events while on the waiting list for CABG was 3 per 10,000 patients per day within the first 90 days (184 events in 9935 patients with a mean of 59 days at risk). Risk factors associated with an increased risk, and included in the basic risk equation, were age, diabetes, heart failure, previous myocardial infarction and involvement of the left main coronary artery or three-vessel disease. The optimal strategy in terms of cost-effectiveness considerations was a prioritisation strategy employing biomarker information. Evaluating shorter maximum waiting times did not alter the conclusion that a prioritisation strategy with a risk score using estimated glomerular filtration rate (eGFR) was cost-effective. These results were robust to most alternative scenarios investigating other sources of uncertainty. However, the cost-effectiveness of the strategy using a risk score with both eGFR and C-reactive protein (CRP) was potentially sensitive to the cost of the CRP test itself (assumed to be 6 pounds in the base-case scenario).
Formally employing more information in the prioritisation of patients awaiting CABG appears to be a cost-effective approach and may result in improved health outcomes. The most robust results relate to a strategy employing a risk score using conventional clinical information together with a single biomarker (eGFR). The additional prognostic information conferred by collecting the more costly novel circulating biomarker CRP, singly or in combination with other biomarkers, in terms of waiting list prioritisation is unlikely to be cost-effective.
Health technology assessment (Winchester, England). 02/2010; 14(9):1-151, iii-iv.
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C Bojke,
Z Philips, M Sculpher,
P Campion,
H Chrystyn,
S Coulton,
B Cross,
V Morton,
S Richmond,
A Farrin,
G Hill,
A Hilton,
J Miles,
I Russell,
I Chi Kei Wong
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ABSTRACT: BACKGROUND: Pharmaceutical care serves as a collaborative model for medication review. Its use is advocated for older patients, although its cost-effectiveness is unknown. Although the accompanying article on clinical effectiveness from the RESPECT (Randomised Evaluation of Shared Prescribing for Elderly people in the Community over Time) trial finds no statistically significant impact on prescribing for older patients undergoing pharmaceutical care, economic evaluations are based on an estimation, rather than hypothesis testing. AIM: To evaluate the cost-effectiveness of pharmaceutical care for older people compared with usual care, according to National Institute for Health and Clinical Excellence (NICE) reference case standards. METHODS: An economic evaluation was undertaken in which NICE reference case standards were applied to data collected in the RESPECT trial. RESULTS: On average, pharmaceutical care is estimated to cost an incremental pound10 000 per additional quality-adjusted life year (QALY). If the NHS's cost-effectiveness threshold is between pound20 000 and pound30 000 per extra QALY, then the results indicate that pharmaceutical care is cost-effective despite a lack of statistical significance to this effect. However, the statistical uncertainty surrounding the estimates implies that the probability that pharmaceutical care is not cost-effective lies between 0.22 and 0.19. Although results are not sensitive to assumptions about costs, they differ between subgroups: in patients aged >75 years pharmaceutical care appears more cost-effective for those who are younger or on fewer repeat medications. CONCLUSION: Although pharmaceutical care is estimated to be cost-effective in the UK, the results are uncertain and further research into its long-term benefits may be worthwhile.
British Journal of General Practice 01/2010; 60(570):20-7. · 1.83 Impact Factor
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L W Turnbull,
S R Brown,
C Olivier,
I Harvey,
J Brown,
P Drew,
A Hanby,
A Manca,
V Napp, M Sculpher,
L G Walker,
S Walker
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ABSTRACT: To determine whether the addition of magnetic resonance imaging (MRI) to current patient evaluation by triple assessment would aid tumour localisation within the breast and thus reduce the reoperation rate in women with primary breast tumours who are scheduled for wide local excision (WLE), and to assess whether the addition of MRI would be cost-effective for the UK NHS.
A multicentre, randomised controlled, open, parallel group trial with equal randomisation. The main design was supplemented with a qualitative study to assess patients' experiences of the treatment process and care pathway, and involved the development of a non-scheduled standardised interview (NSSI).
The study took place at 45 hospitals throughout the UK.
Women aged 18 years or over with biopsy-proven primary breast cancer who had undergone triple assessment, were scheduled for WLE, and were capable of providing written informed consent.
Patients were randomised to receive MRI or no MR1. Randomisation was performed using minimisation, incorporating a random element. All MRI was performed at 1.5 T or 1.0 T with a dedicated bilateral breast coil.
The primary end point of the trial was the reoperation rate. Secondary outcome measures included discrepancies between imaging and histopathology, and the effectiveness of using both procedures; change in clinical management after using MRI; the clinical significance of MRI-only-detected lesions; the rate of interventions; the ipsilateral tumour recurrence rate; patient quality of life (QoL); and cost-effectiveness.
From a total of 1623 patients, 816 were randomised to MRI and 807 to no MRI. No differences in reoperation rates were found between the two groups of patients [MRI patients 18.75%, no MRI 19.33%, difference 0.58%, 95% confidence interval (CI) -3.24 to 4.40]. Therefore, the addition of MRI to conventional triple assessment was not found to be statistically significantly associated with a reduced reoperation rate (odds ratio = 0.96, 95% CI 0.75-1.24, p = 0.7691). The best agreement between all imaging modalities and histopathology with regard to tumour size and extent of disease was found in patients over 50 years old with ductal tumours NST and who were node negative. In the imaging arm, mastectomy was found to be pathologically avoidable for 16 (27.6%) out of 58 patients who underwent the procedure. There were no significant differences between the groups regarding the proportion of patients receiving chemotherapy, radiotherapy or additional adjuvant therapies, as well as for local recurrence-free interval rates and QoL. An acceptable NSSI was developed for use in this population of patients. Economic analysis found no difference in outcomes between the two trial arms.
The addition of MRI to triple assessment did not result in a reduction in operation rates, and the use of MRI would thus consume extra resource with few or no benefits in terms of cost-effectiveness or HRQoL. However, MRI showed potential to improve tumour localisation, and preoperative biopsy of MRI-only-detected lesions is likely to minimise the incidence of inappropriate mastectomy.
Current Controlled Trials ISRCTN57474502.
Health technology assessment (Winchester, England). 01/2010; 14(1):1-182.
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ABSTRACT: This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of rimonabant for the treatment of obese or overweight patients based upon a review of the manufacturer's submission to the National Centre for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's main evidence came from four randomised controlled trials. Rimonabant resulted in a significantly greater benefit than placebo for all primary weight loss outcomes. At 1 year, rimonabant had a statistically significant beneficial effect on systolic blood pressure, high-density lipoprotein cholesterol, triglycerides and fasting plasma glucose in diabetics and non-diabetics, and glycosylated haemoglobin in diabetics. Improvements were maintained over 2 years with rimonabant; withdrawal of rimonabant at 1 year resulted in a reduction in weight loss until there was no difference from placebo at 2 years. Psychiatric adverse events were experienced by 26% and 14% of rimonabant and placebo patients respectively; figures for symptoms of depression were 9% and 5% respectively. Pairwise comparisons of orlistat, sibutramine and rimonabant showed beneficial effects of rimonabant over orlistat and sibutramine for weight loss outcomes; however, response hurdles imposed on orlistat or sibutramine in clinical practice may not have been applied in the orlistat and sibutramine trials. The manufacturer's Markov cohort model evaluated rimonabant versus orlistat, sibutramine and diet and exercise alone for three base-case populations. The incremental cost-effectiveness ratio (ICER) of rimonabant varied from 10,534 pounds to 13,236 pounds per quality-adjusted life-year (QALY) versus diet and exercise, to 8977 pounds to 12,138 pounds per QALY versus orlistat, to 1463 pounds to 3908 pounds per QALY versus sibutramine. In subgroup analysis there was a wider variation in the ICER estimates although none exceeded 20,000 pounds per QALY. The ICER of rimonabant remained under 20,000 pounds per QALY in reanalyses by the manufacturer and the ERG, with the results sensitive to the source of health-related quality of life (HRQoL) benefits in the model. Four treatment strategies were modelled in comparisons of rimonabant versus diet and exercise alone and orlistat and sibutramine in which rimonabant was continued only in patients achieving 5% weight loss at 3, 6, 9 or 12 months. In pairwise comparisons rimonabant remained below a threshold of 30,000 pounds per QALY in 70% of the comparisons reported. The results were most sensitive to the decrement applied to depression and the costs of screening for depression. In conclusion, areas of uncertainty remain in relation to the clinical effectiveness and cost-effectiveness of rimonabant, for example lack of evidence on long-term outcomes and the effect of rimonabant on cardiovascular events, developing diabetes and mortality, and lack of data on the HRQoL benefits associated with rimonabant. The lack of response hurdles applied to sibutramine and orlistat means that the comparator strategies were not considered by the ERG to reflect their respective product licenses or current NHS use. The NICE guidance issued as a result of the STA states that rimonabant is recommended as an adjunct to diet and exercise for adults who are obese or overweight and who have had an inadequate response to, are intolerant of or are contraindicated to orlistat and sibutramine.
Health technology assessment (Winchester, England). 10/2009; 13 Suppl 3:13-22.
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ABSTRACT: To determine the clinical effectiveness and cost-effectiveness of endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic aneurysms (AAAs) in patients at varying levels of risk.
The following bibliographic databases were searched (2005-February 2007): BIOSIS Previews, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, ISI Proceedings, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Science Citation Index and Zetoc Conferences.
A systematic review of the clinical effectiveness of EVAR was performed using standard methods. Meta-analysis was employed to estimate a summary measure of treatment effect on relevant outcomes based on intention to treat analyses. A second systematic review was undertaken to identify existing cost-effectiveness analyses of EVAR compared with open surgery and non-surgical interventions. Two new decision models were developed to inform the review.
Six RCTs were included in the clinical effectiveness review. Thirty-four studies evaluated the role of patients' baseline characteristics in predicting risks of particular outcomes after EVAR. The majority were based on data relating to devices in current use from the EUROSTAR registry. Compared with open repair EVAR reduces operative mortality (odds ratio 0.35, 95% CI 0.19 to 0.63) and medium-term aneurysm-related mortality (hazard ratio 0.49, 95% CI 0.29 to 0.83) but offers no significant difference in all-cause mortality. EVAR is associated with increased rates of complications and reinterventions, which are not offset by any increase in health-related quality of life. EVAR trial 2 comparing EVAR with non-surgical management in patients unfit for open repair found no differences in mortality between groups; however, substantial numbers of patients randomised to non-surgical management crossed over to receive surgical repair of their aneurysm. The cost-effectiveness systematic review identified six published decision models. Both models considered relevant for the decision in the UK concluded that EVAR was not cost-effective on average compared with open repair at a threshold of 20,000 pounds per quality-adjusted life-year (QALY). Another model concluded that EVAR would be on average more cost-effective than no surgical intervention in unfit patients at this threshold. The Medtronic model concluded that EVAR was more cost-effective than open repair for fit patients at this threshold. The York economic evaluations found that EVAR is not cost-effective compared with open repair on average at a threshold of 30,000 pounds per QALY, with the results very sensitive to model assumptions and the baseline risk of operative mortality. Exploratory analysis to evaluate management options in patients unsuitable for open surgery suggested that the cost-effectiveness of EVAR may be sensitive to aneurysm size and patient's age at operation. Indicative modelling suggests that EVAR may be cost-effective for small aneurysms in some patient groups. Ongoing RCTs will provide further evidence relating to these patients.
Open repair is more likely to be cost-effective than EVAR on average in patients considered fit for open surgery. EVAR is likely to be more cost-effective than open repair for a subgroup of patients at higher risk of operative mortality. These results are based on extrapolation of mid-term results of clinical trials. Evidence does not currently support EVAR for the treatment of ruptured aneurysms. Further follow-up of the existing UK trials should be undertaken and the relative costs of procedures and devices should be investigated further.
Health technology assessment (Winchester, England). 10/2009; 13(48):1-189, 215-318, iii.
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S Griffin,
S Walker, M Sculpher,
S White,
S Erhorn,
S Brent,
A Dyker,
L Ferrie,
C Gilfillan,
W Horsley,
K Macfarlane,
S Thomas
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ABSTRACT: This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of cetuximab plus radiotherapy for the treatment of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) considered inappropriate for chemoradiotherapy but appropriate for radiotherapy, based upon the evidence submission from Merck Pharmaceuticals to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The manufacturer's submission was generally of good quality and was an accurate representation of the original reference data. One good-quality randomised controlled trial comparing radiotherapy plus cetuximab with radiotherapy alone in patients with stage III or IV non-metastatic LA SCCHN was included, demonstrating that the duration of locoregional control was significantly longer with radiotherapy plus cetuximab than with radiotherapy alone; also, overall and progression-free survival were significantly longer and the overall response rate was significantly better with the combination therapy. Cetuximab did not exacerbate the common toxic effects associated with radiotherapy of the head and neck. No supporting evidence for these findings are available. The patient population in the trial included a high proportion of patients who would be expected to be suitable for chemoradiotherapy and therefore does not match the population described in the submission's decision problem. Also, the radiotherapy regimens used in the trial are not typical of current UK practice. The ERG considered the manufacturer's economic evaluation to comprise the only relevant evidence to consider for the purposes of this STA. The economic model was considered appropriate for the decision problem. The results suggested that cetuximab plus radiotherapy was cost-effective compared with radiotherapy alone under a broad range of different assumptions on the basis of a cost-effectiveness threshold of 20,000 pounds. In the base case the incremental cost-effectiveness ratio of cetuximab plus radiotherapy compared with radiotherapy alone in the treatment of patients with LA SCCHN was 6390 pounds per additional QALY. Simple sensitivity analyses to examine the robustness of the results were undertaken, suggesting that areas of uncertainty that emerged in the modelling are unlikely to have a material effect on the conclusions. The guidance issued by NICE in May 2007 as a result of the STA states that cetuximab in combination with radiotherapy is not recommended for patients with LA SCCHN.
Health technology assessment (Winchester, England). 06/2009; 13 Suppl 1:49-54.
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D Cooke,
S J Hurel,
A Casbard,
L Steed,
S Walker,
S Meredith,
A J Nunn,
A Manca, M Sculpher,
M Barnard,
D Kerr,
J U Weaver,
J Ahlquist,
S P Newman
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ABSTRACT: To determine whether continuous glucose information provided through use of either the GlucoWatch G2 Biographer or the MiniMed continuous glucose monitoring system (CGMS) results in improved glycated haemoglobin (HbA(1c)) for insulin-treated adults with diabetes mellitus, relative to an attention control and standard care group.
Four hundred and four adults taking at least two daily insulin injections and with two consecutive HbA(1c) values > or = 7.5% were recruited to this randomized controlled trial (RCT). All were trained at baseline to use the same monitor for traditional capillary glucose testing throughout the 18-month study. The CGMS group were asked to wear the device three times during the first 3 months of the trial and on another three occasions thereafter. The GlucoWatch group wore the device a minimum of four times per month and a maximum of four times per week during the first 3 months and as desired for the remainder of the trial. Trained diabetes research nurses used downloaded data to guide therapy adjustments. Proportional reduction in HbA(1c) from baseline to 18 months was the primary outcome measure.
Neither an intention-to-treat nor per-protocol analysis showed improvement in HbA(1c) in the device groups compared with standard care. For the intention-to-treat analysis, when the standard care group was compared with each of the other groups, this equated to differences in mean relative HbA(1c) reduction (95% confidence interval) from baseline to 18 months of 3.5% (-1.3 to 8.3; GlucoWatch), 0.7% (-4.1 to 5.5; CGMS), and -0.1% (-4.6 to 4.3; attention control).
The additional information provided by these devices did not result in improvements in HbA(1c) in this population.
Diabetic Medicine 05/2009; 26(5):540-7. · 2.90 Impact Factor
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S P Newman,
D Cooke,
A Casbard,
S Walker,
S Meredith,
A Nunn,
L Steed,
A Manca, M Sculpher,
M Barnard,
D Kerr,
J Weaver,
J Ahlquist,
S J Hurel
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ABSTRACT: To evaluate whether the additional information provided by minimally invasive glucose monitors results in improved glycaemic control in people with poorly controlled insulin-requiring diabetes, and to assess the acceptability and health economic impact of the devices.
A four-arm randomised controlled trial was undertaken.
Participants were recruited from secondary care diabetes clinics in four hospitals in England.
404 people aged over 18 years with insulin-treated diabetes mellitus (types 1 or 2) for at least 6 months who were receiving two or more injections of insulin daily were eligible. Participants had to have had two glycosylated haemoglobin (HbA1c) values > or = 7.5% in the last 15 months.
Participants were randomised to one of four groups. Two groups received minimally invasive glucose monitoring devices [GlucoWatch Biographer or MiniMed Continuous Glucose Monitoring System (CGMS)]. These groups were compared with an attention control group (standard treatment with nurse feedback sessions at the same frequency as those in the device groups) and a standard control group (reflecting common practice in the clinical management of diabetes in the UK).
Change in HbA1c from baseline to 3, 6, 12 and 18 months was the primary indicator of short- to long-term efficacy in this study. Perceived acceptability of the devices was assessed by use and a self-report questionnaire. A health economic analysis was also performed.
At 18 months all groups demonstrated a decline in HbA1c levels from baseline. Mean percentage changes in HbA1c were -1.4 for the GlucoWatch group, -4.2 for the CGMS group, -5.1 for the attention control group and -4.9 for the standard care control group. At 18 months the relative percentage reduction in HbA1c in each of the intervention arms was less than that in the standard care control group. In the intention to treat analysis no significant differences were found between any of the groups at any of the assessment times. There was no evidence that the additional information provided by the devices resulted in any change in the number or nature of treatment recommendations offered by the nurses. The health economics analysis indicated no advantage in the groups who received the devices; a lower cost and higher benefit were found for the attention control arm. Assessment of device use and acceptability indicated a decline in use of both devices, which was most marked in the GlucoWatch group by 18 months (20% still using GlucoWatch versus 57% still using the CGMS). The GlucoWatch group reported more side effects, greater interference with daily activities and more difficulty in using the device than the CGMS group.
Continuous glucose monitors do not lead to improved clinical outcomes and are not cost-effective for improving HbA1c in unselected individuals with poorly controlled insulin-requiring diabetes. On acceptability grounds the data suggest that the GlucoWatch will not be frequently used by individuals with diabetes because of the large number of side effects.
Health technology assessment (Winchester, England). 05/2009; 13(28):iii-iv, ix-xi, 1-194.
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ABSTRACT: To determine the clinical effectiveness and cost-effectiveness of enhanced external counterpulsation (EECP) compared with usual care and placebo for refractory stable angina and heart failure, and to undertake analyses of the expected value of information to assess the potential value of future research on EECP.
Major electronic databases were searched between November 2007 and March 2008.
A systematic review of the literature was undertaken and a decision model developed to compare EECP treatment with no treatment in adults with chronic stable angina.
Five studies were included in the review. In the Multicenter Study of Enhanced External Counterpulsation (MUST-EECP), time to greater than or equal to 1-mm ST segment depression (exercise-induced ischaemia) was statistically significantly improved in the EECP group compared with the control group (sham EECP), mean difference (MD) 41 seconds [95% confidence interval (CI) 9.10-73.90]. However, there was no statistically significant difference between the EECP and control groups in the change in exercise duration from baseline to end of treatment, self-reported angina episodes or daily nitroglycerin use, and the clinical significance of the limited benefits was unclear. There was also a lack of data on long-term outcomes. There were more withdrawals due to adverse events in the EECP group than in the control group, as well as a greater proportion of patients with adverse events [relative risk (RR) 2.13, 95% CI 1.35-3.38]. The three non-randomised studies compared EECP with elective percutaneous coronary intervention (PCI) and usual care. There was a high risk of selection bias in all three studies and the results should be treated with considerable caution. The study comparing an EECP registry with a PCI registry reported similar 1-year all-cause mortality in both groups. In the Prospective Evaluation of EECP in Congestive Heart Failure (PEECH) trial, patients with heart failure were randomised to EECP or to usual care (pharmacotherapy only). At 6 months post treatment, the proportion of patients achieving at least a 60-second increase in exercise duration was higher in the EECP group (RR 1.39, 95% CI 0.89-2.16), but the proportion with an improvement in peak VO2 was similar in both groups. The clinical significance of this is unclear. The proportion of patients in the EECP group with an improvement in New York Heart Association classification was higher (RR 2.25, 95% CI 1.25-4.06) at 6 months, as was mean exercise duration, MD 34.6 (95% CI -4.86 to 74.06). There were more withdrawals in the EECP group than in the control group as a result of adverse events (RR 1.05, 95% CI 0.67-1.66). There were limitations in the generalisability of results of the trial and, again, a lack of data on long-term outcomes. The review of cost-effectiveness evidence found only one unpublished study but demonstrated that the long-term maintenance of quality of life benefits of EECP is central to the estimate of its cost-effectiveness. The incremental cost-effectiveness ratio of EECP was 18,643 pounds for each additional quality-adjusted life-year (QALY), with a probability of being cost-effective of 0.44 and 0.70 at cost-effectiveness thresholds of 20,000 pounds and 30,000 pounds per QALY gained respectively. Results were sensitive to the duration of health-related quality of life (HRQoL) benefits from treatment.
The results from a single randomised controlled trial (MUST-EECP) do not provide firm evidence of the clinical effectiveness of EECP in refractory stable angina or in heart failure. High-quality studies are required to investigate the benefits of EECP, whether these outweigh the common adverse effects and its long-term cost-effectiveness in terms of quality of life benefits.
Health technology assessment (Winchester, England) 05/2009; 13(24):iii-iv, ix-xi, 1-90. · 4.26 Impact Factor
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D. Cooke,
S. J. Hurel,
A. Casbard,
L. Steed,
S. Walker,
S. Meredith,
A. J. Nunn,
A. Manca, M. Sculpher,
M. Barnard,
D. Kerr,
J. U. Weaver,
J. Ahlquist,
S. P. Newman
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ABSTRACT: Aims To determine whether continuous glucose information provided through use of either the GlucoWatch G2 Biographer or the MiniMed continuous glucose monitoring system (CGMS) results in improved glycated haemoglobin (HbA1c) for insulin-treated adults with diabetes mellitus, relative to an attention control and standard care group.Methods Four hundred and four adults taking at least two daily insulin injections and with two consecutive HbA1c values ≥ 7.5% were recruited to this randomized controlled trial (RCT). All were trained at baseline to use the same monitor for traditional capillary glucose testing throughout the 18-month study. The CGMS group were asked to wear the device three times during the first 3 months of the trial and on another three occasions thereafter. The GlucoWatch group wore the device a minimum of four times per month and a maximum of four times per week during the first 3 months and as desired for the remainder of the trial. Trained diabetes research nurses used downloaded data to guide therapy adjustments. Proportional reduction in HbA1c from baseline to 18 months was the primary outcome measure.Results Neither an intention-to-treat nor per-protocol analysis showed improvement in HbA1c in the device groups compared with standard care. For the intention-to-treat analysis, when the standard care group was compared with each of the other groups, this equated to differences in mean relative HbA1c reduction (95% confidence interval) from baseline to 18 months of 3.5% (−1.3 to 8.3; GlucoWatch), 0.7% (−4.1 to 5.5; CGMS), and −0.1% (−4.6 to 4.3; attention control).Conclusions The additional information provided by these devices did not result in improvements in HbA1c in this population.
Diabetic Medicine 04/2009; 26(5):540 - 547. · 2.90 Impact Factor
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ABSTRACT: To determine the clinical effectiveness, safety and cost-effectiveness of continuous positive airway pressure (CPAP) devices for the treatment of obstructive apnoea-hypopnoea syndrome (OSAHS), compared with the best supportive care, placebo and dental devices.
The main search was of fifteen electronic databases, including MEDLINE, EMBASE and the Cochrane Library, up to November 2006.
Randomised controlled trials (RCTs) comparing CPAP with best supportive/usual care, placebo, and dental devices in adults with a diagnosis of OSAHS were included. The primary outcomes of interest were subjective daytime sleepiness assessed by the Epworth Sleepiness Scale (ESS) and objective sleepiness assessed by the Maintenance of Wakefulness Test (MWT) and the Multiple Sleep Latency Test (MSLT). A new economic model was developed to assess incremental cost per quality-adjusted life-year (QALY). The cost-effectiveness of CPAP was compared with that of the use of dental devices and conservative management. The costs and QALYs were compared over a lifetime time horizon. Effectiveness was based on the RCT evidence on sleepiness symptoms (ESS), which was 'mapped' to utilities using individual patient data from a subset of studies. Utilities were expressed on the basis of generic HRQoL instruments [the EQ-5D (EuroQoL-5 Dimensions) in the base-case analysis]. The base-case analysis focused on a male aged 50. A series of subgroup and scenario analyses were also undertaken.
The searches yielded 6325 citations, from which 48 relevant clinical effectiveness studies were identified, 29 of these providing data on daytime sleepiness. The majority of the included RCTs did not report using an adequate method of allocation concealment or use an intention-to-treat analysis. Only the studies using a sham CPAP comparator were double blinded. There was a statistically significant benefit with CPAP compared with control (placebo and conservative treatment/usual care) on the ESS [mean difference (MD) -2.7 points, 95% CI -3.45 to -1.96]. However, there was statistical heterogeneity, which was reduced when trials were subgrouped by severity of disease. There was also a significant benefit with CPAP compared with usual care on the MWT. There was a non-statistically significant difference between CPAP and dental devices (six trials) in the impact on daytime sleepiness (ESS) among a population with moderate symptom severity at baseline (MD -0.9, 95% CI -2.1 to 0.4). A review of five studies evaluating the cost-effectiveness of CPAP was undertaken. All existing cost-effectiveness studies had limitations; therefore a new economic model was developed, based on which it was found that, on average, CPAP was associated with higher costs and benefits than dental devices or conservative management. The incremental cost per QALY gained of CPAP was below 20,000 pounds in the base-case analysis and most alternative scenarios. There was a high probability of CPAP being more cost-effective than dental devices and conservative management for a cost-effectiveness threshold of 20,000 pounds per QALY gained.
CPAP is an effective and cost-effective treatment for OSAHS compared with conservative/usual care and placebo in populations with moderate to severe daytime sleepiness, and there may be benefits when the disease is mild. Dental devices may be a treatment option in moderate disease but some uncertainty remains. Further research would be potentially valuable, particularly investigation of the effectiveness of CPAP for populations with mild sleepiness and further trials comparing CPAP with dental devices.
Health technology assessment (Winchester, England) 02/2009; 13(4):iii-iv, xi-xiv, 1-119, 143-274. · 4.26 Impact Factor
