Garside R, Pitt M, Somerville M, Stein K, Price A, Gilbert N
Peninsula Technology Assessment Group, Peninsula Medical School, Universities of Exeter and Plymouth, Exeter, UK.
Health Technol Assess. 2006 Mar;10(8):1-142, iii-iv. doi: 10.3310/hta10080.
To assess what is known about the effectiveness, safety, affordability, cost-effectiveness and organisational impact of endoscopic surveillance in preventing morbidity and mortality from adenocarcinoma in patients with Barrett's oesophagus. In addition, to identify important areas of uncertainty in current knowledge for these programmes and to identify areas for further research.
Electronic databases up to March 2004. Experts in Barrett's oesophagus from the UK.
A systematic review of the effectiveness of endoscopic surveillance of Barrett's oesophagus was carried out following methodological guidelines. Experts in Barrett's oesophagus from the UK were invited to contribute to a workshop held in London in May 2004 on surveillance of Barrett's oesophagus. Small group discussion, using a modified nominal group technique, identified key areas of uncertainty and ranked them for importance. A Markov model was developed to assess the cost-effectiveness of a surveillance programme for patients with Barrett's oesophagus compared with no surveillance and to quantify important areas of uncertainty. The model estimates incremental cost--utility and expected value of perfect information for an endoscopic surveillance programme compared with no surveillance. A cohort of 1000 55-year-old men with a diagnosis of Barrett's oesophagus was modelled for 20 years. The base case used costs in 2004 and took the perspective of the UK NHS. Estimates of expected value of information were included.
No randomised controlled trials (RCTs) or well-designed non-randomised controlled studies were identified, although two comparative studies and numerous case series were found. Reaching clear conclusions from these studies was impossible owing to lack of RCT evidence. In addition, there was incomplete reporting of data particularly about cause of death, and changes in surveillance practice over time were mentioned but not explained in several studies. Three cost--utility analyses of surveillance of Barrett's oesophagus were identified, of which one was a further development of a previous study by the same group. Both sets of authors used Markov modelling and confined their analysis to 50- or 55-year-old white men with gastro-oesophageal reflux disease (GORD) symptoms. The models were run either for 30 years or to age 75 years. As these models are American, there are almost certainly differences in practice from the UK and possible underlying differences in the epidemiology and natural history of the disease. The costs of the procedures involved are also likely to be very different. The expert workshop identified the following key areas of uncertainty that needed to be addressed: the contribution of risk factors for the progression of Barrett's oesophagus to the development of high-grade dysplasia (HGD) and adenocarcinoma of the oesophagus; possible techniques for use in the general population to identify patients with high risk of adenocarcinoma; effectiveness of treatments for Barrett's oesophagus in altering cancer incidence; how best to identify those at risk in order to target treatment; whether surveillance programmes should take place at all; and whether there are clinical subgroups at higher risk of adenocarcinoma. Our Markov model suggests that the base case scenario of endoscopic surveillance of Barrett's oesophagus at 3-yearly intervals, with low-grade dysplasia surveyed yearly and HGD 3-monthly, does more harm than good when compared with no surveillance. Surveillance produces fewer quality-adjusted life-years (QALYs) for higher cost than no surveillance, therefore it is dominated by no surveillance. The cost per cancer identified approaches pound 45,000 in the surveillance arm and there is no apparent survival advantage owing to high recurrence rates and increased mortality due to more oesophagectomies in this arm. Non-surveillance continues to cost less and result in better quality of life whatever the surveillance intervals for Barrett's oesophagus and dysplastic states and whatever the costs (including none) attached to endoscopy and biopsy as the surveillance test. The probabilistic analyses assess the overall uncertainty in the model. According to this, it is very unlikely that surveillance will be cost-effective even at relatively high levels of willingness to pay. The simulation showed that, in the majority of model runs, non-surveillance continued to cost less and result in better quality of life than surveillance. At the population level (i.e. people with Barrett's oesophagus in England and Wales), a value of pound 6.5 million is placed on acquiring perfect information about surveillance for Barrett's oesophagus using expected value of perfect information (EVPI) analyses, if the surveillance is assumed to be relevant over 10 years. As with the one-way sensitivity analyses, the partial EVPI highlighted recurrence of adenocarcinoma of the oesophagus (ACO) after surgery and time taken for ACO to become symptomatic as particularly important parameters in the model.
The systematic review concludes that there is insufficient evidence available to assess the clinical effectiveness of surveillance programmes of Barrett's oesophagus. There are numerous gaps in the evidence, of which the lack of RCT data is the major one. The expert workshop reflected these gaps in the range of topics raised as important in answering the question of the effectiveness of surveillance. Previous models of cost-effectiveness have most recently shown that surveillance programmes either do more harm than good compared with no surveillance or are unlikely to be cost-effective at usual levels of willingness to pay. Our cost--utility model has shown that, across a range of values for the various parameters that have been chosen to reflect uncertainty in the inputs, it is likely that surveillance programmes do more harm than good -- costing more and conferring lower quality of life than no surveillance. Probabilistic analysis shows that, in most cases, surveillance does more harm and costs more than no surveillance. It is unlikely, but still possible, that surveillance may prove to be cost-effective. The cost-effectiveness acceptability curve, however, shows that surveillance is unlikely to be cost-effective at either the 'usual' level of willingness to pay ( pound 20,000-30,000 per QALY) or at much higher levels. The expected value of perfect information at the population level is pound 6.5 million. Future research should target both the overall effectiveness of surveillance and the individual elements that contribute to a surveillance programme, particularly the performance of the test and the effectiveness of treatment for both Barrett's oesophagus and ACO. In addition, of particular importance is the clarification of the natural history of Barrett's oesophagus.
评估关于内镜监测在预防巴雷特食管患者腺癌所致发病和死亡方面的有效性、安全性、可负担性、成本效益及组织影响的已知情况。此外，确定这些项目当前知识中重要的不确定领域，并确定进一步研究的领域。
截至2004年3月的电子数据库。英国巴雷特食管领域的专家。
按照方法学指南对巴雷特食管内镜监测的有效性进行系统综述。邀请英国巴雷特食管领域的专家参加2004年5月在伦敦举行的关于巴雷特食管监测的研讨会。采用改良的名义群体技术进行小组讨论，确定关键的不确定领域并对其重要性进行排序。开发了一个马尔可夫模型，以评估巴雷特食管患者监测项目与不监测相比的成本效益，并量化重要的不确定领域。该模型估计了内镜监测项目与不监测相比的增量成本-效用和完全信息的期望值。对1000名55岁诊断为巴雷特食管的男性队列进行了20年的建模。基础病例采用2004年的成本，并采用英国国民医疗服务体系的视角。纳入了信息期望值的估计。
未发现随机对照试验（RCT）或设计良好的非随机对照研究，尽管发现了两项比较研究和众多病例系列。由于缺乏RCT证据，无法从这些研究中得出明确结论。此外，数据报告不完整，尤其是关于死亡原因的报告，并且在几项研究中提到了监测实践随时间的变化，但未作解释。确定了三项巴雷特食管监测的成本-效用分析，其中一项是同一组先前研究的进一步发展。两组作者均使用马尔可夫模型，并将分析局限于有胃食管反流病（GORD）症状的50岁或55岁白人男性。模型运行30年或至75岁。由于这些模型是美国的，几乎可以肯定在实践中与英国存在差异，并且在疾病的流行病学和自然史方面可能存在潜在差异。所涉及程序的成本也可能有很大不同。专家研讨会确定了以下需要解决的关键不确定领域：巴雷特食管进展为高级别异型增生（HGD）和食管腺癌的危险因素的作用；在一般人群中用于识别腺癌高危患者的可能技术；巴雷特食管治疗在改变癌症发生率方面的有效性；如何最好地识别高危人群以进行靶向治疗；是否应该进行监测项目；以及是否存在腺癌高危的临床亚组。我们的马尔可夫模型表明，与不监测相比，每3年对巴雷特食管进行内镜监测的基础病例方案，低级别异型增生每年监测，HGD每3个月监测，弊大于利。监测产生的质量调整生命年（QALY）比不监测少，但成本更高，因此被不监测所主导。监测组中每发现一例癌症的成本接近45,000英镑，并且由于该组中高复发率和更多食管切除术导致的死亡率增加，没有明显的生存优势。无论巴雷特食管和异型增生状态的监测间隔如何，以及作为监测测试的内镜检查和活检的成本（包括无成本）如何，不监测的成本持续较低，生活质量更好。概率分析评估了模型中的总体不确定性。据此，即使在相对较高的支付意愿水平下，监测也极不可能具有成本效益。模拟显示，在大多数模型运行中，不监测的成本持续低于监测，生活质量更好。在人群水平（即英格兰和威尔士的巴雷特食管患者），如果假设监测在10年内相关，使用完全信息期望值（EVPI）分析得出，获取关于巴雷特食管监测的完全信息的价值为650万英镑。与单向敏感性分析一样，部分EVPI突出显示食管腺癌（ACO）手术后的复发以及ACO出现症状所需的时间是模型中特别重要的参数。
系统综述得出结论，现有证据不足以评估巴雷特食管监测项目的临床有效性。证据存在许多空白，其中缺乏RCT数据是主要的。专家研讨会在提出的作为回答监测有效性问题重要的一系列主题中反映了这些空白。先前的成本效益模型最近表明，与不监测相比，监测项目要么弊大于利，要么在通常的支付意愿水平下不太可能具有成本效益。我们的成本-效用模型表明，在为反映输入中的不确定性而选择的各种参数的一系列值范围内，监测项目可能弊大于利——成本更高，生活质量低于不监测。概率分析表明，在大多数情况下，监测的危害更大且成本高于不监测。监测不太可能，但仍有可能被证明具有成本效益。然而，成本效益可接受性曲线表明，在“通常”的支付意愿水平（每QALY 20,000 - 30,000英镑）或更高水平下，监测不太可能具有成本效益。人群水平的完全信息期望值为650万英镑。未来的研究应针对监测的总体有效性以及构成监测项目的各个要素，特别是检测的性能以及巴雷特食管和ACO治疗的有效性。此外，特别重要的是阐明巴雷特食管的自然史。
