科技日报（2011-4-27）--在老年痴呆症药物memantine的制造商提交了一份研究资料的补充分析后，德国质量和效率医疗保健研究所 （IQWiG）看到了一个证据，即为期至少6个月的治疗后该药物对认知功能带来好处，并且在日常生活方面也有向好的迹象。这改变了2009年IQWiG的 第一份效益评估的结论。IQWiG一再要求制造商梅尔茨提供一份更新的研究问题分析报告。

对厂家来说更多的努力也可能是值得的

IQWiG 主任Jürgen Windeler对新的评估结果评论如下：“与许多其他项目一样，研究所在对memantine的评估中也面临着在证据不足。如果是这样的话，我们会在消 除这些差距方面提出一些建议。有时要求补充新的研究；有时只需制造商提供或补充已有的数据，比如memantine，额外的努力最后得到了回报。”

在IQWiG进行第一次评审时，两项研究的数据不翼而飞

在 德国，批准用于治疗中度至重度阿尔茨海默病的药物memantine使用商品名“Axura”和“Ebixa”进行销售。在联邦委员会（的G - BA）筹办并于2009年9月出版的第一次效益评估中，IQWiG发现没有证据表明阿尔茨海默氏症患者可受益于memantine。但是，由于种种原因， 两项研究的有关资料遗失了，制造商没有提供给IQWiG。

补充分析没有考虑到所有相关研究

在2010年初，梅尔茨向G- BA提交了这两项研究的结果，以及大量研究的补充分析。随后，IQWiG在2010年8月以工作文件（PDF格式，2 MB）的形式发表了第二次评估。然而，这并没有改变第一次报告的结论。这也是基于IQWiG不能利用梅尔茨所提供的补充分析这一事实。例如，除其他问题 外，梅尔茨再次未能包括所有的相关研究。然而，IQWiG在其工作文件中说明了应如何分析这些数据。

没有恶化也可能意味着一种改善

梅尔茨终于在2010年10月向G-BA提交了对数据进行了适当处理的补充分析。这些都是“应答分析”。这种类型的分析是由对多少病人治疗后健康状况得到了显着改善即“应答者”的统计而来。
为此需要指明在病人身上发生多大变化可以归为有所改善。然后，在安慰剂组和memantine组统计所有达到这一指标的病人的数量。在进行性疾病如阿尔茨海默氏症中，没有恶化也可算是一项进步。

日常生活活动向好的征兆

正如现在提交的分析所显示的，最多服用6个月的memantine，短期和长期记忆（认知功能）恶化的患者的数量比较对照组少。IQWiG将此归为改善的一个证据。
这 样一个有利于memantine的差异还体现在日常生活（例如关于个人卫生）活动方面，但是差别相当小。此外，相对于“认知功能”的结果来说，该研究也没 有通过长年的测试来说明应该根据什么准则将病人列为治疗应答者。这就给对该结果的理解带来了更大的不确定性。因此，总体上IQWiG基于这一结果认为服用 memantine有向好的迹象而不是证据。

缺乏长期研究

目前还不清楚memantine是否提高生活质量，因为目前的 研究结果还不足以得出任何结论。现在提交的认知功能和日常生活活动的结果都有一定的时间限制，因为没有一项研究的持续时间超过6个月。Jürgen Windeler说，“我们还没有长期的研究。然而，特别是对于老年性痴呆这样需要常年服药的疾病来说，长期研究是迫切需要的。”



原文如下：

Germany: Memantine as Possible Alzheimer's Treatment

ScienceDaily (Apr. 27, 2011)— After the manufacturer of the Alzheimer's drug memantine submitted a supplementary analysis of study data, the German Institute for Quality and Efficiency in Health Care (IQWiG) sees proof of a benefit of the drug for cognitive function, as well as indications of a benefit for activities of daily living, at least for a treatment period of 6 months. This changes the conclusions of the first IQWiG benefit assessment of 2009. IQWiG had repeatedly called upon the manufacturer Merz to provide a renewed analysis of study data appropriate to the research question.
Additional effort may also be worthwhile for manufacturers
IQWiG's Director Jürgen Windeler comments on the new assessment result: "As in many other projects, in the assessment of memantine the Institute was also confronted with gaps in the evidence. If this is the case, then we make suggestions as to how these gaps can be closed. Sometimes additional new studies are required; sometimes it suffices if the manufacturer provides or supplements data already available, as was the case for memantine. In the end, the additional effort paid off."
In the first IQWiG assessment, data from two studies were missing
In Germany the drug memantine is marketed under the tradenames "Axura" and "Ebixa," and is approved for the treatment of moderate to severe Alzheimer's disease. In a first benefit assessment, prepared after commissioning by the Federal Joint Committee (G-BA) and published in September 2009, IQWiG found no proof that patients with Alzheimer's disease could benefit from memantine. However, among other things, relevant information on two studies was missing, which the manufacturer had not provided to IQWiG.
Additional analysis did not consider all of the relevant studies
At the beginning of 2010, Merz submitted the results of these two studies, as well as additional analyses of a larger number of studies, to the G-BA. IQWiG subsequently published a second assessment in the form of a working paper (PDF, 2 MB) in August 2010. However, this did not change the conclusions of the first report. This was also due to the fact that IQWiG could not utilize the additional analyses as presented by Merz. For example, among other things, Merz had again failed to include all of the relevant studies. However, in its working paper IQWiG described how an appropriate analysis of the data could be performed.
Absence of deterioration may also mean an improvement
These additional analyses, in which the data were processed appropriately, were finally submitted by Merz to the G-BA in October 2010. These were "responder analyses." In this type of analysis, a count is made of how many patients experience a notable improvement in their health status after treatment, i.e. are "responders."
For this purpose it is specified how big this difference has to be in a patient in order to be classified as an improvement. Then, both in the placebo and in the memantine groups, all patients are counted who at least achieved this improvement. In the case of a progressive disease such as Alzheimer's, the absence of deterioration may also be regarded as an improvement.
Indications of a benefit for activities of daily living
As the analysis now submitted shows, the number of patients whose short- and long-term memory (cognitive function) notably deteriorated over a period of at most 6 months was lower in the memantine group. IQWiG classifies this result as proof of a benefit.
Such a difference in favour of memantine was also shown for activities of daily living (e.g. concerning personal hygiene); however, this was considerably smaller. In addition, in contrast to the outcome "cognitive function," the criteria according to which patients were classified as treatment responders have not proved themselves through year-long testing in studies. This leads to greater uncertainty in the interpretation of results. Consequently, overall IQWiG assumes an indication -- not proof -- of a benefit of treatment with memantine for this outcome.
Long-term studies are lacking
It remains unclear whether memantine improves quality of life, as for this outcome the studies available still allow no conclusions to be drawn. The results for cognitive function and activities of daily living now submitted only apply with time restrictions, as none of the studies lasted longer than 6 months. "We still have no long-term studies. However, particularly for Alzheimer's drugs this type of study is urgently required, as they are usually taken for several years," says Jürgen Windeler.