目的:数字灌注测量,有时再加上冷酷的挑战,已被广泛用作评价雷诺现象(RP)药物治疗的试验的客观结果,除了患者报告的结局或在初步研究中建立概念验证。然而,数字灌注是否是RP试验中临床结局的有效替代指标,目前尚未被研究.这项研究的主要目的是评估数字灌注的潜在代用性,通过结合个人水平和试验水平的数据。
方法:我们使用了一系列n-of-1试验的个体数据,和来自网络荟萃分析的试验数据。我们通过数字灌注和临床结果(R2ind)之间的确定系数来估计个体水平的代孕。我们进一步计算了治疗效果对临床结果和数字灌注之间的决定系数,在个体水平(R2TEInd)和试验水平(R2trial),使用非加权线性回归,通过自举计算他们的95%CI。
结果:最终分析包括33例患者和24项试验的结果。在个人层面,静息和响应各种降温试验的数字灌注与临床结果之间没有相关性(最高R2ind为0.03[-0.07;0.09]),和R2TEinf也非常低0.07[0;0.29]。在审判层面,R2试验的最高值为0.1[0;0.477]。
结论:数字灌注,在休息或应对寒冷的挑战时,不管用什么方法,不符合RP试验中现有患者报告结局的有效替代标准.
OBJECTIVE: Measurement of digital perfusion, sometimes coupled with a cold challenge, has been widely used as an objective outcome in trials evaluating drug therapies in
RP, in addition to patient-reported outcomes or to establish the proof-of-concept in preliminary studies. However, whether digital perfusion is a valid surrogate for clinical outcomes in
RP trials has never been explored. The principal aim of this study was to evaluate the potential surrogacy of digital perfusion, by combining individual-level and trial-level data.
METHODS: We used individual data from a series of n-of-1 trials, and trial data from a network meta-analysis. We estimated individual-level surrogacy through coefficients of determination between digital perfusion and clinical outcomes (R2ind). We further calculated the coefficients of determination between treatment effect on the clinical outcomes and on digital perfusion, at the individual level (R2TEind) and at the trial level (R2trial), using non-weighted linear regression, with their 95% CI calculated through bootstrapping.
RESULTS: Results from 33 patients and 24 trials were included in the final analysis. At the individual level, there was no correlation between digital perfusion and clinical outcomes at rest and in response to various cooling tests (the highest R2ind was 0.03 [-0.07, 0.09]), and R2TEind was also very low 0.07 (0, 0.29). At the trial level, the highest value of R2trial was 0.1 (0, 0.477).
CONCLUSIONS: Digital perfusion, at rest or in response to a cold challenge, and whatever the method used, does not fulfil the criteria of a valid surrogate for existing patient-reported outcomes in
RP trials.