Supplementary Material for: Proposal for Standardization of Primary and Secondary Outcomes in Patients with Active, Moderate-to-Severe Graves’ Orbitopathy

Standardization of treatment outcomes in randomized clinical trials (RCTs) for active, moderate-to-severe Graves’ orbitopathy (GO) is needed to make results of different RCTs comparable and to draw sound conclusions on the efficacy of a given treatment. Both subjective patient-reported outcome (PRO) and objective clinician-reported outcome (CRO) are important in this regard. In this paper, it is proposed that primary PRO should be the evaluation of treatment-related changes in the quality of life by the use of a validated and disease-specific questionnaire (GO-QoL). The proposed primary CRO is a revised composite index, which includes only objective items and provides an overall assessment of the effects of treatment. Secondary outcomes should also be provided in RCTs to show the effects of treatment on individual features of GO, as well on persistence of activity (by the 7-item Clinical Activity Score), safety, relapses of GO, need for subsequent medical and/or surgical treatments, and other indicators (orbital volume, cytokines, TSH receptor antibody levels). Assessment of the overall response to treatment by primary and secondary outcomes should be made 3 months after treatment completion.

为使不同随机对照试验（RCT）的结果具有可比性，并针对特定治疗方案的疗效得出可靠结论，亟需对活动性中重度格雷夫斯眼病（GO）的随机对照试验治疗结局进行标准化。在此研究场景中，主观的患者报告结局（PRO）与客观的临床医师报告结局（CRO）均具有重要价值。本文提出，主要患者报告结局应采用经过验证的疾病特异性问卷（GO-QoL）评估治疗相关的生活质量变化；本文推荐的主要临床医师报告结局为一项修订后的复合指标，该指标仅纳入客观条目，可全面评估治疗的整体效果。随机对照试验还应报告次要结局，以体现治疗对格雷夫斯眼病各临床特征的影响，以及疾病活动度的持续情况（采用7项临床活动度评分）、治疗安全性、格雷夫斯眼病复发情况、后续药物和/或手术治疗的需求，以及其他相关指标（眶容积、细胞因子、促甲状腺素受体抗体水平）。需在治疗结束后3个月，基于主要与次要结局对治疗的整体应答情况进行评估。