West Midlands Health Technology Assessment Collaboration, Department of Public Health, Epidemiology & Biostatistics, University of Birmingham, Birmingham, UK.
Health Technol Assess. 2011 May;15 Suppl 1:43-50. doi: 10.3310/hta15suppl1/05.
This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of prucalopride for the treatment of women with chronic constipation in whom standard laxative regimens have failed to provide adequate relief. The ERG report is based on the manufacturer's submission (MS) to the National Institute for Health and Clinical Excellence as part of the single technology appraisal process. In the submission, quality-of-life data [Patient Assessment of Constipation Quality of Life (PAC-QOL) and Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaires] from trials of prucalopride were extrapolated to EQ-5D (European Quality of Life-5 Dimensions) data and used to inform effectiveness in an economic model. Response rates to prucalopride were derived from observed response rates in trials, defined as the proportion of patients achieving an average of three or more spontaneous complete bowel movements over the 4- or 12-week trial periods. Adult (18-64 years) and elderly (≥ 65 years) patients were considered separately in the model. Cost-effectiveness was determined from estimated improvements in EQ-5D and anticipated response rates, adjusted for baseline severity of chronic constipation. The ERG considered that the patients participating in these trials were not representative of those in the licensed indication. They were not all refractory to laxatives, and baseline EQ-5D scores showed a large spread in quality of life, with many patients experiencing little baseline dissatisfaction. The mapping of quality-of-life data from trials (PAC-QOL and PAC-SYM data) to EQ-5D was unclear and invalidated. The assumption of the long-term effectiveness and safety of prucalopride to 1 year was considered unjustified. There was no justification or sources given for coefficients used to predict effectiveness in the economic model, and no costs other than the cost of prucalopride were incorporated into the model. Owing to the many areas of uncertainty, particularly the effectiveness of prucalopride in the licensed patient group and its long-term effectiveness and safety, it was considered that the MS provided no evidence for whether prucalopride is effective or not in women with laxative-refractory chronic constipation. Further subgroup analysis of the actual patient group of interest may have better guided decision-making. However, long-term efficacy data, with validated estimates of quality of life incorporated in a well-founded model, would be important for an evidence-based judgement to be made.
本文总结了专家组（ERG）关于普芦卡必利治疗女性慢性便秘的临床疗效和成本效益的报告，这些女性对标准泻药治疗方案没有充分缓解。专家组的报告是基于制造商向国家卫生与临床优化研究所提交的单一技术评估申请（MS）。在提交的材料中，普芦卡必利试验的生活质量数据[便秘患者生活质量评估量表（PAC-QOL）和便秘症状评估量表（PAC-SYM）]被外推到 EQ-5D（欧洲生命质量-5 维度）数据中，并用于经济模型中的疗效评估。普芦卡必利的应答率是从试验中观察到的应答率中得出的，定义为在 4 或 12 周试验期间，达到平均 3 次或更多自发性完全排便的患者比例。模型中分别考虑了成年（18-64 岁）和老年（≥65 岁）患者。成本效益是根据预期的 EQ-5D 改善和预期的应答率来确定的，同时考虑了慢性便秘基线严重程度的调整。专家组认为，参与这些试验的患者不能代表许可适应症中的患者。他们并非都对泻药有抗药性，而且基线 EQ-5D 评分显示生活质量存在很大差异，许多患者基线时的不满程度较低。从试验（PAC-QOL 和 PAC-SYM 数据）到 EQ-5D 的生活质量数据的映射不清楚且无效。普芦卡必利长期有效性和安全性至 1 年的假设被认为是不合理的。经济模型中用于预测疗效的系数没有依据或来源，除了普芦卡必利的成本外，模型中没有纳入其他成本。由于存在许多不确定因素，特别是普芦卡必利在许可患者群体中的疗效及其长期有效性和安全性，因此认为 MS 并未提供关于普芦卡必利在对泻药有抗药性的慢性便秘女性中的有效性的证据。对实际感兴趣的患者群体进行进一步的亚组分析可能会更好地指导决策。然而，长期疗效数据，结合纳入有充分依据的模型的生活质量的验证估计，对于做出基于证据的判断非常重要。
