This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19.
什么是double-blind
In many trials, no one—not even the research team—knows who gets the treatment, the placebo, or another intervention. When participants, family members, and staff all are “blind” to the treatment while the study is underway, the study is called a “double-blind, placebo-controlled” clinical trial.
"Despite the limitations, single-arm trials may be the only (or one of few) options for trials evaluating therapies for which placebos are not ethical and options for controlled trials are limited. Single-arm trials have been commonly implemented in oncology."
我在制药公司工作了很多年，管过很多clinical trials. Phase 3 study can be randomize 尤其是急性严重疾病，从ethical 方面考虑试验可能设计成open label. 另外病人不管分到哪个组只要病情严重恶化就可以用其它药了。美国的临床实验非常讲究ethical, 不可能分到placebo 就宁愿病人面临生命危险而不给其他药。placebo 通常是指standard care, 在楼主这种情况下能够拿到血清的话是会给用的 https://bbs.wenxuecity.com/rdzn/4408692.html
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)
Study Details Tabular ViewNo Results PostedDisclaimerHow to Read a Study Record Study Description Go to Brief Summary: This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.
Condition or disease Intervention/treatment Phase
COVID-19
Other: PlaceboDrug: Remdesivir
Phase 3
Detailed Description:
This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms.
The initial sample size is projected to be 572 subjects to achieve 400 subjects with a "recovered" status (per the primary objective). The primary analysis will be based on those subjects enrolled in order to 400 recoveries. An additional analysis of the moderate severity subgroup (those with baseline status of "Hospitalized, requiring supplemental oxygen" or "Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care") is also of public health importance. Hence, enrollment will be permitted until the date of April 20, 2020 to ensure 400 recoveries and provide additional data about this important subgroup. With recent enrollment rates, the total sample size may be 600 to over 800.
Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29 as an outpatient. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and OP swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, Day 15 and 29 visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and may also be conducted by phone.
All subjects will undergo a series of efficacy, safety, and laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Days 1 (prior to infusion) and Days 3, 5, 8, and 11 (while hospitalized). OP swabs and blood (serum only) plus safety laboratory tests will be collected on Day 15 and 29 (if the subject attends an in-person visit or are still hospitalized).
The primary outcome is time to recovery by Day 29. A key secondary outcome evaluates treatment-related improvements in the 8-point ordinal scale at Day 15. As little is known about the clinical course of COVID-19, a pilot study will be used for a blinded sample size reassessment.
Study Design Go to
Study Type :
Interventional (Clinical Trial)
Estimated Enrollment :
800 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults
Actual Study Start Date :
February 21, 2020
Estimated Primary Completion Date :
April 1, 2023
Estimated Study Completion Date :
April 1, 2023
Arms and Interventions Go to
Arm Intervention/treatment
Placebo Comparator: Placebo 200 mg of Remdesivir placebo administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir placebo while hospitalized for up to a 10 days total course. n=286.
Other: Placebo The supplied placebo lyophilized formulation is identical in physical appearance to the active lyophilized formulation and contains the same inactive ingredients. Alternatively, a placebo of normal saline of equal volume may be given if there are limitations on matching placebo supplies.
Experimental: Remdesivir 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10 days total course. n=286.
Drug: Remdesivir Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.
placebo不是standard of care. placebo是专门生产的，外观和药品完全一致的（几乎完全，特殊情况有的时候会有微小差别）药品，里面除了没有API，其他的excepients 和药品应该是一样的。用placebo的目的就是用来blind的。让病人和医生无法从外观上猜测出哪个是药品，哪个是placebo。Remdisivir是冻干剂，placebo也是设计成一样的包装了，administration方法也是一致的。在那个临床试验的网站上可以看到一点的。
standard of care 是当时业界通过的医疗此病的标准，不是什么placebo。我不知道这位是管clinical trial的哪一块的，这样的说法明显不对。
关于对这个trial是如何操作的，下面是summary的第一句
This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19.
什么是double-blind
In many trials, no one—not even the research team—knows who gets the treatment, the placebo, or another intervention. When participants, family members, and staff all are “blind” to the treatment while the study is underway, the study is called a “double-blind, placebo-controlled” clinical trial.
有专门的CRO，他们拿到药，根据protocol，会randomize药瓶，然后在上面贴好标签，按需要发到每个做临床的医院，医生 来源: mickey222 于 2020-05-22 06:48:00 [档案] [博客] [旧帖] [给我悄悄话] 本文已被阅读： 6 次 (897 bytes) 字体：调大/重置/调小 | 加入书签 | 打印 | 所有跟帖 | 加跟贴 | 当前最热讨论主题
收到药，只看见一个编号，不知道里面是什么，病人更加不会知道了。physician's brochure里面有很详细的指导如何给药的。而那个CRO保存database，里面哪个标号对应的是药还是placebo，他们知道，但是CRO不到最后揭盲，是不会告诉任何公司，医生，病人的。否则就是违反 GCP了。
临床试验也不是一次性收100个病人大家同时做，病人都是一个个收的，因为有很多手续的，也需要符合很多条件的病人才可以收的，所以某个试验中心或者医院收了病人，医生会通知公司，公司会通知那个CRO，他们就会寄送药品去哪个试验中心或者医院。
大部分生药公司都在临床试验中大量使用CRO，因为这样可以build很多barrier，避免很多信息泄露，同时也是术业有专攻。
随机双盲当然最好，但由于具体条件的不同，很多试验并不随机，也不双盲，甚至并不单盲。尽管如此，它们也是临床试验，也有价值。
“，很多试验并不随机，也不双盲，甚至并不单盲”你的这种临床试验，新药在FDA过不了，
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059315/
没时间就读2.1即可。
如果这也太多，就读下面一段。
"Despite the limitations, single-arm trials may be the only (or one of few) options for trials evaluating therapies for which placebos are not ethical and options for controlled trials are limited. Single-arm trials have been commonly implemented in oncology."
这不想着得给人家做个示范么
一个大牛，不经常发言，每个月要审核很多临床用药的，看了中坛的跟帖，没说话.......
人家没说话，你怎么知道人家去看了
说呀
说了，大牛不经常发言的
能跟牛人说上话，你也是大牛啊
我就一家庭妇女
管孩子，管家，都是工作。有人觉得容易，其实是非常的不容易。非常重要的工作。
很多工业界混不好华人的去FDA做reviewer。FDA里面reviewer的structure比较flat，也没啥可以竞争的了，不是reviewer就是senior reviewer。不少是华人，因为需要的语言功能比较少，很多reviewer就懂她自己那一块。没有全局观。没有华人做到Janet Woodcock那位子的，所以不知道是什么大牛。呵呵。Janet还是很牛的。是个大牛。
我只有一次跟她一个桌子吃饭的机会。没能真正的认识这样的牛人。唯一可以跟她提的跟她差不多的一个FDA华人，我知道，可是不是做新药的。有个发明是行业标准。是个男的。
phase 3 也是这要求？
不需要对照组？
中国内的试验没做成，在美国疫情爆发期有许多病人。这家公司对这个药的研发已经投入很多，难道药厂以后还会计划做双盲的？不做blinding可能出于什么考虑？想听听你的看法。
这次gilead那么多临床试验，不是gilead做三期的本意，是特殊时期为了救人。
我在制药公司工作了很多年，管过很多clinical trials. Phase 3 study can be randomize 尤其是急性严重疾病，从ethical 方面考虑试验可能设计成open label. 另外病人不管分到哪个组只要病情严重恶化就可以用其它药了。美国的临床实验非常讲究ethical, 不可能分到placebo 就宁愿病人面临生命危险而不给其他药。placebo 通常是指standard care, 在楼主这种情况下能够拿到血清的话是会给用的 https://bbs.wenxuecity.com/rdzn/4408692.html
其实不懂是没问题的，问题是只懂一点就觉得自己都懂了。对网友报告治病经历打压就更缺乏同情心了。这些人在伦理方面需要补课。
我不做infectious disease的。我觉得 Gilead本身是比较谨慎的一个公司，所以他自己设计的临床对风险的考虑比较多。何况这个病毒本身比较tricky，也不知道它是怎么来的，变化很快，我都不知道这个病的standard of care是什么，看起来好像每个州，国家都有自己的一套，很乱，重症病人的死亡率高。Remdisevir本来只是用于Ebola的，没有做冠状病毒的1期，2期，现在这个病高度政治化，所以Gilead比较严谨，怕落下口实。open label有利于降低风险。
如果其他sponsor做，他家也乐见其成，如果他们效果好，Gilead再上也不迟，就这个病毒这么强的感染能力，我觉得这个病的传播还会延续一段时间，到时候需要病人应该不是大问题。
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)
Study Details Tabular View No Results Posted Disclaimer How to Read a Study Record Study Description Go toThis study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms.
The initial sample size is projected to be 572 subjects to achieve 400 subjects with a "recovered" status (per the primary objective). The primary analysis will be based on those subjects enrolled in order to 400 recoveries. An additional analysis of the moderate severity subgroup (those with baseline status of "Hospitalized, requiring supplemental oxygen" or "Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care") is also of public health importance. Hence, enrollment will be permitted until the date of April 20, 2020 to ensure 400 recoveries and provide additional data about this important subgroup. With recent enrollment rates, the total sample size may be 600 to over 800.
Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29 as an outpatient. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and OP swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, Day 15 and 29 visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and may also be conducted by phone.
All subjects will undergo a series of efficacy, safety, and laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Days 1 (prior to infusion) and Days 3, 5, 8, and 11 (while hospitalized). OP swabs and blood (serum only) plus safety laboratory tests will be collected on Day 15 and 29 (if the subject attends an in-person visit or are still hospitalized).
The primary outcome is time to recovery by Day 29. A key secondary outcome evaluates treatment-related improvements in the 8-point ordinal scale at Day 15. As little is known about the clinical course of COVID-19, a pilot study will be used for a blinded sample size reassessment.
Study Design Go toplacebo不是standard of care. placebo是专门生产的，外观和药品完全一致的（几乎完全，特殊情况有的时候会有微小差别）药品，里面除了没有API，其他的excepients 和药品应该是一样的。用placebo的目的就是用来blind的。让病人和医生无法从外观上猜测出哪个是药品，哪个是placebo。Remdisivir是冻干剂，placebo也是设计成一样的包装了，administration方法也是一致的。在那个临床试验的网站上可以看到一点的。
standard of care 是当时业界通过的医疗此病的标准，不是什么placebo。我不知道这位是管clinical trial的哪一块的，这样的说法明显不对。
它的早期数据已被FDA用作授予Remdesivir EUA 的依据。
论文也刚新鲜出炉，在这里：
Remdesivir for the Treatment of Covid-19 — Preliminary Report
第一阶段已经结束了，安慰剂组的病人也给予用药
Inside the NIH’s controversial decision to stop its big remdesivir study
不过它还有第二阶段的新trial。
Gilead被中国抢注专利之后的回应，迅速放弃孤儿药认证，给两个open label trials增加同情用药渠道等做法，都给人不错的印象。
Standard of Care确实很杂乱，有个一线医生说，we throw everything at it except the kitchen sink.
临床试验也是一大堆蜂拥而上。
整个事情的关键词是病人家属说的“安慰剂组”。 换成“常规治疗组”或“对照组”，就不奇怪了。 来源: 虎嗅蔷薇 于 2020-05-22
在健坛会时常看到患者和家属来问问题或者写长篇分享诊疗过程，里面有各种医学名词概念混乱, 叙述过程颠三倒四, 或重要事实语焉不详或者对不上需要澄清, 占不小比例。
我的判断是她母亲参加的是Gilead的open label trial。被分到常规治疗组。被她理解为安慰剂组。
言之凿凿：医生打电话告诉她，妈妈被分在安慰剂组了。
我相信她的每个字写的，所以才有疑问啊，因为她写的情况不可能存在。
很内敛，很hold的住。坚持自己的信念。不为外部所动。