ClinStat GmbH, Cologne, Germany.
Institute for Health Services Research and Health Economics, Medical Faculty, Heinrich-Heine University Düsseldorf, Gebäude 12.49, Moorenstraße 5, 40225, Düsseldorf, Germany.
Eur J Health Econ. 2019 Feb;20(1):45-57. doi: 10.1007/s10198-018-0981-3. Epub 2018 Apr 25.
The decision matrix applied by the Institute for Quality and Efficiency in Health Care (IQWiG) for the quantification of added benefit within the early benefit assessment of new pharmaceuticals in Germany with its nine fields is quite complex and could be simplified. Furthermore, the method used by IQWiG is subject to manifold criticism: (1) it is implicitly weighting endpoints differently in its assessments favoring overall survival and, thereby, drug interventions in fatal diseases, (2) it is assuming that two pivotal trials are available when assessing the dossiers submitted by the pharmaceutical manufacturers, leading to far-reaching implications with respect to the quantification of added benefit, and, (3) it is basing the evaluation primarily on dichotomous endpoints and consequently leading to an information loss of usable evidence.
To investigate if criticism is justified and to propose methodological adaptations.
Analysis of the available dossiers up to the end of 2016 using statistical tests and multinomial logistic regression and simulations.
It was shown that due to power losses, the method does not ensure that results are statistically valid and outcomes of the early benefit assessment may be compromised, though evidence on favoring overall survival remains unclear. Modifications, however, of the IQWiG method are possible to address the identified problems.
By converging with the approach of approval authorities for confirmatory endpoints, the decision matrix could be simplified and the analysis method could be improved, to put the results on a more valid statistical basis.
德国卫生保健质量与效率研究所（IQWiG）在其早期新药效益评估中应用的决策矩阵，共有九个领域，用于量化附加效益，该矩阵非常复杂，可以简化。此外，IQWiG 使用的方法受到多方面的批评：（1）在评估中隐含地对终点进行不同权重，有利于总体生存率，从而有利于治疗致命疾病的药物干预；（2）在评估制药商提交的档案时，假设存在两个关键试验，这导致对附加效益的量化产生深远影响；（3）它主要基于二分类终点进行评估，从而导致有用证据的信息丢失。
调查批评是否有依据，并提出方法学上的调整建议。
使用统计检验和多项逻辑回归以及模拟方法，对截至 2016 年底的可用档案进行分析。
结果表明，由于效力损失，该方法不能确保结果在统计学上有效，早期效益评估的结果可能会受到影响，尽管总体生存的结果仍不清楚。然而，对 IQWiG 方法的修改是可能的，可以解决已确定的问题。
通过与确认性终点的审批机构方法趋同，可以简化决策矩阵，并改进分析方法，使结果建立在更有效的统计基础上。
