Proposal for Standardization of Primary and Secondary Outcomes in Patients with Active, Moderate-to-Severe Graves'...

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.