Background We analysed the impact of clinical study design for oncological pharmaceuticals on the subsequent price negotiations after early benefit assessment between pharmaceutical companies and the German National Association of Statutory Health Insurance Funds. The analysis was conducted for all oncology pharmaceuticals that underwent the early benefit assessment in Germany since its introduction in 2011 up to September 2016. Methods It was differentiated between additive (new therapy in addition to baseline therapy) and substitutive study designs (baseline therapy to be replaced). The study design was derived from the dossiers of the pharmaceutical companies submitted to the Federal Joint Committee. Subgroup specific costs in case of granted added benefit were calculated as annual therapy costs and compared with the costs of the appropriate comparators to quantify price premiums. Further price influencing factors were analysed in univariate and multivariate regression analysis considering the budget impact for the statutory health insurance as well. Results The mean and the median of the additive premiums for substitutive designs (€50,477.68 and €49,841.24) were higher than for additive designs, if the comparator was different to best supportive care (€48,750.00 and €42,820.44). The mean multiplicative premium for the substitutive designs was 15.07 versus 2.29 for the additive designs. EU-Prices and target population size had a significant effect on the reimbursement. The adjusted R-square in the log Premium OLS-regressions reached 0.708 when including all explanatory variables and considering interaction between target population and annual costs of the comparator. Conclusions Study design as an additional important influencing factor of the negotiations next to those stated in the framework agreement was identified and verified. Therefore, study design should be considered by pharmaceutical companies and by decision makers and payers within strategic price planning as a potential predictor. For some specific categories the number of cases was small. Further analyses should be performed when more oncology pharmaceuticals have passed the early benefit assessment.

中文翻译：

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在德国进行早期收益评估后，附加或替代临床研究设计对肿瘤药物议定补偿的影响

背景我们分析了制药公司和德国国家法定健康保险基金协会进行的早期收益评估后，肿瘤药物临床研究设计对随后价格谈判的影响。自2011年推出以来至2016年9月，对在德国进行过早期获益评估的所有肿瘤药物进行了分析。替换）。研究设计源自提交给联邦联合委员会的制药公司档案。在获得额外收益的情况下，将亚组的特定费用计算为年度治疗费用，并与适当比较者的费用进行比较以量化价格溢价。在单变量和多变量回归分析中，还考虑了法定健康保险的预算影响，进一步分析了价格影响因素。结果如果比较者不同于最佳支持治疗，替代设计的附加费的均值和中位数（50,477.68欧元和49,841.24欧元）要高于附加设计（48,750.00欧元和42,820.44欧元）。替代设计的平均乘法溢价为15.07，而加法设计为2.29。欧盟价格和目标人口规模对费用的支付产生了重大影响。Premium OLS回归日志中的调整后R平方达到0。708，包括所有解释变量，并考虑目标人群与比较者的年度费用之间的相互作用。结论确定并核实了研究设计，该研究设计是框架协议中所述谈判之外的其他重要影响因素。因此，药物设计公司，战略价格计划中的决策者和付款人应将研究设计视为潜在的预测指标。对于某些特定类别，案件数量很少。当更多的肿瘤药物通过早期获益评估时，应进行进一步分析。结论确定并核实了研究设计，该研究设计是框架协议中所述谈判之外的其他重要影响因素。因此，药物设计公司，战略价格计划中的决策者和付款人应将研究设计视为潜在的预测指标。对于某些特定类别，案件数量很少。当更多的肿瘤药物通过早期获益评估时，应进行进一步分析。结论确定并核实了研究设计，该研究设计是框架协议中所述谈判之外的其他重要影响因素。因此，药物设计公司，战略价格计划中的决策者和付款人应将研究设计视为潜在的预测指标。对于某些特定类别，案件数量很少。当更多的肿瘤药物通过早期获益评估时，应进行进一步分析。