Holbrook J T, Meinert C L, Van Natta M L, Davis M, Hubbard L, Jabs D A
Center for Clinical Trials, Johns Hopkins University, 615 N Wolfe St., Room 5010, Baltimore, MD 21205.
Arch Ophthalmol. 2001 Apr;119(4):554-63. doi: 10.1001/archopht.119.4.554.
To evaluate photographic measures of cytomegalovirus (CMV) retinitis as surrogate outcomes for changes in vision in patients with CMV retinitis related to the acquired immunodeficiency syndrome.
Data from 3 clinical trials of CMV retinitis treatments were analyzed. Two photographic assessments of retinitis in eyes involved at baseline were evaluated: progression (lesion border movement > or = 750 microm or occurrence of a new lesion) and change in area of retina involved with retinitis. Vision measures were decline in best-corrected visual acuity and change in visual field. Photographic measures were evaluated as surrogate outcomes based on 4 criteria: (1) association with vision measure; (2) ability to account for treatment-related differences in vision measure; (3) data completeness; and (4) sample size requirements.
Data from 1001 involved eyes (666 patients) were analyzed. Progression and change in area involved were predictive of declines in vision measures, accounted for 50% and 66% of the treatment effect on visual field, and were available from 93% and 64% of involved eyes, respectively. Sample size estimates for a clinical trial were smallest with progression as the design outcome.
Progression and change in area involved met the first and second criteria for surrogate outcomes for visual field loss; a complete evaluation for visual acuity decline was not possible because treatment-related differences were not observed. Progression met the logistical and sample size criteria better than change in area of retina involved with retinitis.
评估巨细胞病毒（CMV）视网膜炎的摄影测量指标，作为与获得性免疫缺陷综合征相关的CMV视网膜炎患者视力变化的替代结局。
分析了3项CMV视网膜炎治疗临床试验的数据。对基线时受累眼睛的视网膜炎进行了两项摄影评估：进展情况（病变边界移动≥750微米或出现新病变）和视网膜炎累及的视网膜面积变化。视力测量指标为最佳矫正视力下降和视野变化。根据4项标准对视网膜炎摄影测量指标作为替代结局进行评估：（1）与视力测量指标的相关性；（2）解释视力测量指标中与治疗相关差异的能力；（3）数据完整性；（4）样本量要求。
分析了来自1001只受累眼睛（666例患者）的数据。进展情况和累及面积变化可预测视力测量指标的下降，分别占治疗对视野影响的50%和66%，分别有93%和64%的受累眼睛可获得这两项指标。以进展情况作为设计结局的临床试验样本量估计最小。
进展情况和累及面积变化符合视野丧失替代结局的第一和第二项标准；由于未观察到与治疗相关的差异，因此无法对视敏度下降进行全面评估。进展情况在后勤和样本量标准方面比视网膜炎累及的视网膜面积变化更符合要求。
