Mangiapane Sandra, Velasco Garrido Marcial
Technische Universität Berlin, Berlin, Deutschland.
GMS Health Technol Assess. 2009 Aug 26;5:Doc12. doi: 10.3205/hta000074.
The different actors involved in health system decision-making and regulation have to deal with the question which are valid parameters to assess the health value of health technologies.So called surrogate endpoints represent in the best case preliminary steps in the casual chain leading to the relevant outcome (e. g. mortality, morbidity) and are not usually directly perceptible by patients. Surrogate endpoints are not only used in trials of pharmaceuticals but also in studies of other technologies. Their use in the assessment of the benefit of a health technology is however problematic.IN THIS REPORT WE INTEND TO ANSWER THE FOLLOWING RESEARCH QUESTIONS: Which criteria need to be fulfilled for a surrogate parameter to be considered a valid endpoint? Which methods have been described in the literature for the assessment of the validity of surrogate endpoints? Which methodological recommendations concerning the use of surrogate endpoints have been made by international HTA agencies? Which place has been given to surrogate endpoints in international and German HTA reports?For this purpose, we choose three different approaches. Firstly, we conduct a review of the methodological literature dealing with the issue of surrogate endpoints and their validation. Secondly, we analyse current methodological guidelines of HTA agencies members of the International network of agencies for Health Technology Assessment (INAHTA) as well as of agencies concerned with assessments for reimbursement purposes. Finally, we analyse the outcome parameter used in a sample of HTA reports available for the public.The analysis of methodological guidelines shows a very cautious position of HTA institutions regarding the use of surrogate endpoints in technology assessment. Surrogate endpoints have not been prominently used in HTA reports. None of the analysed reports based its conclusions solely on the results of surrogate endpoints. The analysis of German HTA reports shows a similar pattern.The validation of a surrogate endpoint requires extensive research, including randomized controlled trials (RCT) assessing clinical relevant endpoints. The validity of a surrogate parameter is rather technology-specific than disease-specific. Thus - even in the case of apparently similar technologies - it is necessary to validate the surrogate for every single technology (i. e. for every single active agent).The use of surrogate endpoints in the assessment of the benefit of health technologies is still to be seen very critically.
哪些是评估卫生技术健康价值的有效参数。所谓的替代终点在最佳情况下代表了通向相关结果（如死亡率、发病率）的因果链中的初步步骤，并且通常患者无法直接感知。替代终点不仅用于药物试验，也用于其他技术的研究。然而，它们在评估卫生技术效益方面的应用存在问题。
在本报告中，我们打算回答以下研究问题：替代参数要被视为有效终点需要满足哪些标准？文献中描述了哪些评估替代终点有效性的方法？国际卫生技术评估机构就替代终点的使用提出了哪些方法学建议？替代终点在国际和德国卫生技术评估报告中处于什么地位？
为此，我们选择了三种不同的方法。首先，我们对涉及替代终点及其验证问题的方法学文献进行综述。其次，我们分析国际卫生技术评估机构网络（INAHTA）成员机构以及负责报销评估的机构当前的方法学指南。最后，我们分析公开可得的卫生技术评估报告样本中使用的结果参数。
对方法学指南的分析表明，卫生技术评估机构在技术评估中对替代终点的使用持非常谨慎的态度。替代终点在卫生技术评估报告中并未得到突出使用。所分析的报告中没有一份仅基于替代终点的结果得出结论。对德国卫生技术评估报告的分析也显示出类似的模式。
替代终点的验证需要广泛的研究，包括评估临床相关终点的随机对照试验（RCT）。替代参数的有效性更多地是针对特定技术而非特定疾病。因此，即使在技术看似相似的情况下，也有必要针对每一项技术（即针对每一种活性成分）验证替代终点。
在评估卫生技术效益时对替代终点的使用仍需非常审慎地看待。
