Department of Oncology, Queen's University, Kingston, Ontario, Canada; Department of Public Health Sciences, Queen's University, Kingston, Ontario, Canada; Division of Cancer Care and Epidemiology, Queen's University, Kingston, Ontario, Canada.
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
ESMO Open. 2021 Jun;6(3):100117. doi: 10.1016/j.esmoop.2021.100117. Epub 2021 Apr 20.
The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a validated, widely used tool developed to score the clinical benefit from cancer medicines reported in clinical trials. ESMO-MCBS scores assume valid research methodologies and quality trial implementation. Studies incorporating flawed design, implementation, or data analysis may generate outcomes that exaggerate true benefit and are not generalisable. Failure to either indicate or penalise studies with bias undermines the intention and diminishes the integrity of ESMO-MCBS scores. This review aimed to evaluate the adequacy of the ESMO-MCBS to address bias generated by flawed design, implementation, or data analysis and identify shortcomings in need of amendment.
As part of a refinement of the ESMO-MCBS, we reviewed trial design, implementation, and data analysis issues that could bias the results. For each issue of concern, we reviewed the ESMO-MCBS v1.1 approach against standards derived from Helsinki guidelines for ethical human research and guidelines from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, the Food and Drugs Administration, the European Medicines Agency, and European Network for Health Technology Assessment.
Six design, two implementation, and two data analysis and interpretation issues were evaluated and in three, the ESMO-MCBS provided adequate protections. Seven shortcomings in the ability of the ESMO-MCBS to identify and address bias were identified. These related to (i) evaluation of the control arm, (ii) crossover issues, (iii) criteria for non-inferiority, (iv) substandard post-progression treatment, (v) post hoc subgroup findings based on biomarkers, (vi) informative censoring, and (vii) publication bias against quality-of-life data.
Interpretation of the ESMO-MCBS scores requires critical appraisal of trials to understand caveats in trial design, implementation, and data analysis that may have biased results and conclusions. These will be addressed in future iterations of the ESMO-MCBS.
欧洲肿瘤内科学会-临床获益量表（ESMO-MCBS）是一种经过验证的、广泛使用的工具，用于对临床试验报告的癌症药物的临床获益进行评分。ESMO-MCBS 评分假设采用了有效的研究方法和高质量的试验实施。纳入设计、实施或数据分析有缺陷的研究可能会产生夸大真实获益且不具有普遍性的结果。未能指明或惩罚存在偏倚的研究，会破坏 ESMO-MCBS 评分的初衷并降低其完整性。本综述旨在评估 ESMO-MCBS 对因设计、实施或数据分析缺陷而产生的偏倚的处理能力，并确定需要修订的不足之处。
作为对 ESMO-MCBS 进行细化的一部分，我们回顾了可能影响结果的试验设计、实施和数据分析问题。对于每个关注的问题，我们根据赫尔辛基人类伦理研究指南、人用药品技术要求国际协调理事会、美国食品和药物管理局、欧洲药品管理局和欧洲卫生技术评估网络的指南，对 ESMO-MCBS v1.1 方法进行了评估。
评估了 6 个设计问题、2 个实施问题和 2 个数据分析和解释问题，在其中 3 个问题中，ESMO-MCBS 提供了充分的保护。确定了 ESMO-MCBS 识别和处理偏倚的 7 个不足之处。这些不足之处与（i）对照臂的评估、（ii）交叉问题、（iii）非劣效性标准、（iv）标准后进展治疗、（v）基于生物标志物的事后亚组发现、（vi）信息性删失和（vii）对生活质量数据的发表偏倚有关。
解释 ESMO-MCBS 评分需要对试验进行批判性评估，以了解可能影响结果和结论的试验设计、实施和数据分析中的注意事项。这些将在 ESMO-MCBS 的未来迭代中得到解决。
