最新法国临床试验结果:羟氯喹(hydroxychloroquine)与阿奇霉素(azithromycin)组合促进新冠病毒(COVID-19)转阴。
摘要如下:
36位确诊病人,分两组:治疗组20人,对照组16人。明签实验(非双盲)
所有参试者,无症状17%,上呼吸道感染症状61%,肺炎22%
治疗组口服羟氯喹200毫克,每日三次,共10天。如果有肺炎症状,加阿奇霉素(第一天口服500毫克,以后,每天250毫克,服四天)。追踪观察时间14天。结果如下:
第六天,治疗组转阴率70%(14人),对照组12.5% (2人). P<0.001. 其中羟氯喹加阿奇霉素100%(6人)转阴。单用羟氯喹(14人)转阴率57%(8人). 而且临床症状越明显,治疗效果越显著。
今早,美国国家食品药物管理局特批此药应用于临床。
以上数据的统计分析:
a.我们希望看到治疗有效,所以对两比例之差,p1-p2,计算了它的99%置信度下单边置信区间。计算使用了特别针对小样本的R-软件包,ExactCIdiff。
b.我们选择99%的置信度,而不是常用的95%,因为这里的样本量很小,建立治疗有效非常关键,统计推论必须高度可靠。
c. 美国FDA决定将这种药物用于COVID-19,对此特朗普总统在Twitter上发表了评论。
令trt1 =羟氯喹,trt2 =阿奇霉素。
情况1:trt(trt 1或trt 2)与安慰剂:
n1 = 20,x = 14; n2 = 16,y = 2:p1-p2属于单边区间[0.1997,1] – 99%置信度(trt与安慰剂)
情况2:trt1 + trt2与安慰剂:
n1 = 6,x = 6; n2 = 16,y = 2:p1-p2属于单边区间[0.35233,1] – 99%置信度(trt1 + trt2与安慰剂比较)
情况3:trt1与安慰剂:
n1 = 14,x = 8; n2 = 16,y = 2:p1-p2属于单边区间[0.02786,1]– 99%置信度(trt1与安慰剂)
d。 结论:所有三个区间都属于(0,1],大于零,表明具有统计学意义,即该治疗对抗COVID-19有效。
The statistical analysis of the above data set (by W.W., 2020-03-21):
a. We wish to see the treatment (trt) is better than the placebo, so 99% one-sided confidence intervals for the difference of two proportions, p1-p2, are calculated using an R-package, ExactCIdiff, that focuses on small samples.
b. We pick the 99% confidence level rather than the commonly used 95% since the sample sizes here are very small and the recommendation of establishing the trt is so critical: the statistical
inference must be highly reliable.
c. US FDA made the decision of using this drug for COVID-19, and President Trump made a comment on Twitter.
Let trt1=羟氯喹, trt2=阿奇霉素.
Case 1: trt (trt 1 or trt 2) vs placebo:
n1=20, x=14; n2=16, y=2: p1-p2 in [0.1997, 1] – 99% confidence (trt vs placebo)
Case 2: trt 1+ trt2 vs placebo:
n1=6, x=6; n2=16, y=2: p1-p2 in [0.35233, 1] – 99% confidence (trt1+trt2 vs placebo)
Case 3: trt1 vs placebo:
n1=14, x=8; n2=16, y=2: p1-p2 in [0.02786, 1] – 99% confidence (trt1 vs placebo)
d. Conclusion:All three intervals belong to (0,1], indicating statistical significance. i.e., the treatment is effective in fighting COVID-19.