最新法國臨床試驗結果:羥氯喹(hydroxychloroquine)與阿奇黴素(azithromycin)組合促進新冠病毒(COVID-19)轉陰。
摘要如下:
36位確診病人,分兩組:治療組20人,對照組16人。明簽實驗(非雙盲)
所有參試者,無症狀17%,上呼吸道感染症狀61%,肺炎22%
治療組口服羥氯喹200毫克,每日三次,共10天。如果有肺炎症狀,加阿奇黴素(第一天口服500毫克,以後,每天250毫克,服四天)。追蹤觀察時間14天。結果如下:
第六天,治療組轉陰率70%(14人),對照組12.5% (2人). P<0.001. 其中羥氯喹加阿奇黴素100%(6人)轉陰。單用羥氯喹(14人)轉陰率57%(8人). 而且臨床症狀越明顯,治療效果越顯著。
今早,美國國家食品藥物管理局特批此藥應用於臨床。
以上數據的統計分析:
a.我們希望看到治療有效,所以對兩比例之差,p1-p2,計算了它的99%置信度下單邊置信區間。計算使用了特別針對小樣本的R-軟件包,ExactCIdiff。
b.我們選擇99%的置信度,而不是常用的95%,因為這裡的樣本量很小,建立治療有效非常關鍵,統計推論必須高度可靠。
c. 美國FDA決定將這種藥物用於COVID-19,對此特朗普總統在Twitter上發表了評論。
令trt1 =羥氯喹,trt2 =阿奇黴素。
情況1:trt(trt 1或trt 2)與安慰劑:
n1 = 20,x = 14; n2 = 16,y = 2:p1-p2屬於單邊區間[0.1997,1] – 99%置信度(trt與安慰劑)
情況2:trt1 + trt2與安慰劑:
n1 = 6,x = 6; n2 = 16,y = 2:p1-p2屬於單邊區間[0.35233,1] – 99%置信度(trt1 + trt2與安慰劑比較)
情況3:trt1與安慰劑:
n1 = 14,x = 8; n2 = 16,y = 2:p1-p2屬於單邊區間[0.02786,1]– 99%置信度(trt1與安慰劑)
d。 結論:所有三個區間都屬於(0,1],大於零,表明具有統計學意義,即該治療對抗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=羥氯喹, trt2=阿奇黴素.
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.