回复 1楼ray_golden的帖子 病人数增加，揭盲日期不变，说明增加的部分可能是已经治疗过的expanded access和compassionate use，应该对primary analysis没有影响。我认为这部分病人主要是扩充safety data和confirm efficacy in the main study. 而且实验中间暗中分析数据，然后为了达到统计显著增加病人数是严重的red flag，我不认为吉利得会这么做。
just my 2 cents, there is a time component in the primary endpoint, time to discharge, death, etc. adding more participants will increase power even the primary analysis timeline is unchanged. certainly there are many other considerations for a mid-study design change but I do suspect drug effect is modest. Hope I am wrong this time... Not really a serious reg flag as there is something call sample size re-estimation.
其实在oncology trial里这种情况很常见。ph1 study show promising data, then expand arms to enroll more patients, sometimes can focus on specific subgroups, sometimes can simply to have more data for safety and/or efficacy and use ph1 for NDA submission. 总之扩招肯定不是坏事。
其实在oncology trial里这种情况很常见。ph1 study show promising data, then expand arms to enroll more patients, sometimes can focus on specific subgroups, sometimes can simply to have more data for safety and/or efficacy and use ph1 for NDA submission. 总之扩招肯定不是坏事。 purified2 发表于 4/10/2020 1:40:00 PM
BREAKING APRIL 10, 2020. “In this cohort of patients HOSPITALIZED for SEVERE Covid-19 who were treated with compassionate-use #remdesivir, clinical improvement was observed in 36 of 53 patients (68%).” Fantastic results for the most seriously ill. For those given this early in the process, results should be much more successful, given prior study data. Specifically, improvement in oxygen-support status was observed in 68% of patients, and overall mortality was 13% over a median follow-up of 18 days. In a recent randomized, controlled trial of lopinavir–ritonavir in patients hospitalized for Covid-19, the 28-day mortality was 22%.10 It is important to note that only 1 of 199 patients in that trial were receiving invasive ventilation at baseline. In case series and cohort studies, largely from China, mortality rates of 17 to 78% have been reported in severe cases, defined by the need for admission to an intensive care unit, invasive ventilation, or both.23-28 64% of remdesivir-treated patients were receiving invasive ventilation at baseline, including 8% who were receiving ECMO, and mortality in this subgroup was 18% (as compared with 5.3% in patients receiving noninvasive oxygen support), and the majority (75%) of patients were male, were over 60 years of age, and had coexisting conditions. https://www.nejm.org/doi/full/10.1056/NEJMoa2007016
Totally different. They are talking about a randomized ph3 not a ph1b expansion...
其实在oncology trial里这种情况很常见。ph1 study show promising data, then expand arms to enroll more patients, sometimes can focus on specific subgroups, sometimes can simply to have more data for safety and/or efficacy and use ph1 for NDA submission. 总之扩招肯定不是坏事。 purified2 发表于 4/10/2020 1:40:00 PM
just my 2 cents, there is a time component in the primary endpoint, time to discharge, death, etc. adding more participants will increase power even the primary analysis timeline is unchanged. certainly there are many other considerations for a mid-study design change but I do suspect drug effect is modest. Hope I am wrong this time... Not really a serious reg flag as there is something call sample size re-estimation. inin 发表于 4/10/2020 11:54:07 AM
I said the same thing yesterday in a private group, i.e., the effect is likely modest. Hope I was wrong about this too!
1. Gilead 在做慈善。做临床试验公司不仅免费提供药，一般还会给病人和医院一定的钱。 2. 病人太多，供不应求。如果是global study 估计一天之内就能enroll 上千人。 3. 药没有 major safety concerns 4. Efficacy not as good as previously predicted.
其实在oncology trial里这种情况很常见。ph1 study show promising data, then expand arms to enroll more patients, sometimes can focus on specific subgroups, sometimes can simply to have more data for safety and/or efficacy and use ph1 for NDA submission. 总之扩招肯定不是坏事。 purified2 发表于 4/10/2020 1:40:50 PM
能不能解释一下为什么从double blind改成open label了？
这位从记录看是多年的川黑吧。现在川黑和5毛重合度很高，都是希望美国越惨越好，然后从中谋利，当然也可能是一人两身份。
原来就是open label吧。重症的study一组5天，一组10天，都是active drug，没什么可blind的。中症的study，原来好像也是这么设计的，现在好像加了一组standard of care，这种医流行病治疗环境，double blind不一定可行。
那你的学生到底是傻还是坏，还是你没教好。
你是认真的？可以去看看有多少药是fail在phase 3上的。另外，可以看看有多少fail的药，在前期试验里其实看到的结果还很不错。
这肯定是不对的韵，太多的药phase 1/2可见效果，但是phase 3就不行了。样本大，结果才可靠。
希望和理性分析有时是不一致的，通常扩大样本是小样本试验结果不够significantly，
我无比希望现在岀现任何有效的药。
说出了心里话
这个楼和无数pump无效“特效药”的楼真实的反映了美国目前的民智
1000个样本的数量已经够多了。我是想不懂， 比如1000个里面，有50个治好了 和 4000里面，有200个治好有区别吗？
感觉像是，1000个里面只有5个真正治好重症的样子。
👍
I said the same thing yesterday in a private group, i.e., the effect is likely modest.
Hope I was wrong about this too!
feel exactly the same as u do
其他几条不了解情况不评价， 单说第一条， Gilead在做慈善？一般临床实验不都是公司提供药给钱吗， 不然为啥进入临床花的钱都是翻着跟头的涨？
我非常希望这个药有效， 或者不管别的什么药有效来消除这场灾难，但Gilead也谈不到做慈善，就是恰巧在做这个药而这个药恰巧有可能对新冠有疗效。 讲起来对Gilead来说反而是好事，因为他们根本不用费力去考虑资金， 在各项审核上肯定也是优先不必排队等的。
Gilead说是还在进行临床实验 实际上是在抓紧时间扩大产能
这个药说不上是特效药 但是肯定是有效药 有可能到一段时间后每个人都要适量服用提高抵抗能力 这时候产能和分配就是大问题
所以一定要产量有几千万剂量甚至上亿之后才能谈上市 但是现在拖着不上市也有悖人伦，毕竟那么多人等着用呢 所以只能拿这个做挡箭牌拖拖时间
这个和氯喹的情况还不一样 氯喹作为老药新用，已经有很成熟的生产方法和产业链，价格也很便宜也没有专利壁垒，就这样现在都还不容易买到
瑞德西韦一定要考虑产能和分配的问题。有关系的可以考察一下现在的同情用药申请的难度，如果申请难度很低，那就说明这个药一定是有效的。
没必要personify一个公司吧
就营业而言，GILD需要salvage在ebola trial中没有成功的一个研发产品
对他而言大部分钱已经投进去了，为肺炎再搞几个trial是no hurt
但也不需要read too much into the efficacy
像楼里其他人说的 这是positive PR
对大众来说，这种情况切忌病急乱投医
看到五毒所抢注专利，就知道药是管用的。
这么多国家没有一个出来说这是特效药的， 估计悬啊。 救命药哪怕不经过双盲， 如果真的有效， 也会用的。