辉瑞95%的有效性报告存在重大漏洞，被学术界质疑涉嫌故意造假

徽剑评：这是一篇质疑辉瑞数据造假的评论，外国网友发给我的，文章里面分析了辉瑞报告的存在的重大问题

1、发现人为筛选结果，删除不利数据

2、评测结果的审核人员是辉瑞公司员工

下面附上原文和汉语翻译：

https://blogs.bmj.com/bmj/2021/01/04/peter-doshi-pfizer-and-modernas-95-effective-vaccines-we-need-more-details-and-the-raw-data/

Peter Doshi: Pfizer and Moderna’s “95% effective” vaccines—we need more details and the raw data

January 4, 2021

Five weeks ago, when I raised questions about the results of Pfizer’s and Moderna’s covid-19 vaccine trials, all that was in the public domain were the study protocols and a few press releases. Today, two journal publications and around 400 pages of summary data are available in the form of multiple reports presented by and to the FDA prior to the agency’s emergency authorization of each company’s mRNA vaccine. While some of the additional details are reassuring, some are not. Here I outline new concerns about the trustworthiness and meaningfulness of the reported efficacy results.

“Suspected covid-19”

All attention has focused on the dramatic efficacy results: Pfizer reported 170 PCR confirmed covid-19 cases, split 8 to 162 between vaccine and placebo groups. But these numbers were dwarfed by a category of disease called “suspected covid-19”—those with symptomatic covid-19 that were not PCR confirmed. According to FDA’s report on Pfizer’s vaccine, there were “3410 total cases of suspected, but unconfirmed covid-19 in the overall study population, 1594 occurred in the vaccine group vs. 1816 in the placebo group.”

With 20 times more suspected than confirmed cases, this category of disease cannot be ignored simply because there was no positive PCR test result. Indeed this makes it all the more urgent to understand. A rough estimate of vaccine efficacy against developing covid-19 symptoms, with or without a positive PCR test result, would be a relative risk reduction of 19% (see footnote)—far below the 50% effectiveness threshold for authorization set by regulators. Even after removing cases occurring within 7 days of vaccination (409 on Pfizer’s vaccine vs. 287 on placebo), which should include the majority of symptoms due to short-term vaccine reactogenicity, vaccine efficacy remains low: 29% (see footnote).

If many or most of these suspected cases were in people who had a false negative PCR test result, this would dramatically decrease vaccine efficacy. But considering that influenza-like illnesses have always had myriad causes—rhinoviruses, influenza viruses, other coronaviruses, adenoviruses, respiratory syncytial virus, etc.—some or many of the suspected covid-19 cases may be due to a different causative agent.

But why should etiology matter? If those experiencing “suspected covid-19” had essentially the same clinical course as confirmed covid-19, then “suspected plus confirmed covid-19” may be a more clinically meaningful endpoint than just confirmed covid-19.

However, if confirmed covid-19 is on average more severe than suspected covid-19, we must still keep in mind that at the end of the day, it is not average clinical severity that matters, it’s the incidence of severe disease that affects hospital admissions. With 20 times more suspected covid-19 than confirmed covid-19, and trials not designed to assess whether the vaccines can interrupt viral transmission, an analysis of severe disease irrespective of etiologic agent—namely, rates of hospitalizations, ICU cases, and deaths amongst trial participants—seems warranted, and is the only way to assess the vaccines’ real ability to take the edge off the pandemic.

There is a clear need for data to answer these questions, but Pfizer’s 92-page report didn’t mention the 3410 “suspected covid-19” cases. Nor did its publication in the New England Journal of Medicine. Nor did any of the reports on Moderna’s vaccine. The only source that appears to have reported it is FDA’s review of Pfizer’s vaccine.

The 371 individuals excluded from Pfizer vaccine efficacy analysis

Another reason we need more data is to analyse an unexplained detail found in a table of FDA’s review of Pfizer’s vaccine: 371 individuals excluded from the efficacy analysis for “important protocol deviations on or prior to 7 days after Dose 2.”  What is concerning is the imbalance between randomized groups in the number of these excluded individuals: 311 from the vaccine group vs 60 on placebo. (In contrast, in Moderna’s trial, there were just 36 participants excluded from the efficacy analysis for “major protocol deviation”—12 vaccine group vs 24 placebo group.)

What were these protocol deviations in Pfizer’s study, and why were there five times more participants excluded in the vaccine group?  The FDA report doesn’t say, and these exclusions are difficult to even spot in Pfizer’s report and journal publication.

Fever and pain medications, unblinding, and primary event adjudication committees

Last month I expressed concern about the potential confounding role of pain and fever medications to treat symptoms. I posited that such drugs could mask symptoms, leading to underdetection of covid-19 cases, possibly in greater numbers in people who received the vaccine in an effort to prevent or treat adverse events. However, it seems their potential to confound results was fairly limited: although the results indicate that these medicines were taken around 3–4 times more often in vaccine versus placebo recipients (at least for Pfizer’s vaccine—Moderna did not report as clearly), their use was presumably concentrated in the first week after vaccine use, taken to relieve post-injection local and systemic adverse events. But the cumulative incidence curves suggest a fairly constant rate of confirmed covid-19 cases over time, with symptom onset dates extending well beyond a week after dosing.

That said, the higher rate of medication use in the vaccine arm provides further reason to worry about unofficial unblinding. Given the vaccines’ reactogenicity, it’s hard to imagine participants and investigators could not make educated guesses about which group they were in.  The primary endpoint in the trials is relatively subjective making unblinding an important concern. Yet neither FDA nor the companies seem to have formally probed the reliability of the blinding procedure, and its effects on the reported outcomes.

Nor do we know enough about the processes of the primary event adjudication committees that counted covid-19 cases. Were they blinded to antibody data and information on patients’ symptoms in the first week after vaccination?  What criteria did they employ, and why, with a primary event consisting of a patient-reported outcome (covid-19 symptoms) and PCR test result, was such a committee even necessary? It’s also important to understand who was on these committees. While Moderna has named its four-member adjudication committee—all university-affiliated physicians—Pfizer’s protocol says three Pfizer employees did the work. Yes, Pfizer staff members.

Vaccine efficacy in people who already had covid?

Individuals with a known history of SARS-CoV-2 infection or previous diagnosis of Covid-19 were excluded from Moderna’s and Pfizer’s trials. But still 1125 (3.0%) and 675 (2.2%) of participants in Pfizer’s and Moderna’s trials, respectively, were deemed to be positive for SARS-CoV-2 at baseline.

Vaccine safety and efficacy in these recipients has not received much attention, but as increasingly large portions of many countries’ populations may be “post-Covid,” these data seem important—and all the more so as the US CDC recommends offering vaccine “regardless of history of prior symptomatic or asymptomatic SARS-CoV-2 infection.” This follows on from the agency’s conclusions, regarding Pfizer’s vaccine, that it had ≥92% efficacy and “no specific safety concerns” in people with previous SARS-CoV-2 infection.

By my count, Pfizer apparently reported 8 cases of confirmed, symptomatic Covid-19 in people positive for SARS-CoV-2 at baseline (1 in the vaccine group, 7 in the placebo group, using the differences between Tables 9 and 10) and Moderna, 1 case (placebo group; Table 12).

But with only around four to 31 reinfections documented globally, how, in trials of tens of thousands, with median follow-up of two months, could there be nine confirmed covid-19 cases among those with SARS-CoV-2 infection at baseline? Is this representative of meaningful vaccine efficacy, as CDC seems to have endorsed? Or could it be something else, like prevention of covid-19 symptoms, possibly by the vaccine or by the use of medicines which suppress symptoms, and nothing to do with reinfection?

We need the raw data

Addressing the many open questions about these trials requires access to the raw trial data. But no company seems to have shared data with any third party at this point.

Pfizer says it is making data available “upon request, and subject to review.” This stops far short of making data publicly available, but at least leaves the door open. How open is unclear, since the study protocol says Pfizer will only start making data available 24 months after study completion.

Moderna’s data sharing statement states data “may be available upon request once the trial is complete.” This translates to sometime in mid-to-late 2022, as follow-up is planned for 2 years.

Things may be no different for the Oxford/AstraZeneca vaccine which has pledged patient-level data “when the trial is complete.” And the ClinicalTrials.gov entry for the Russian Sputnik V vaccine says there are no plans to share individual participant data.

The European Medicines Agency and Health Canada, however, may share data for any authorized vaccines much earlier.  EMA has already pledged to publish the data submitted by Pfizer on its website “in due course,” as has Health Canada.

Peter Doshi, associate editor, The BMJ

Competing interests: I have been pursuing the public release of vaccine trial protocols, and have co-signed open letters calling for independence and transparency in covid-19 vaccine related decision making.

Footnote

Calculations in this article are as follows:  19% = 1 – (8+1594)/(162+1816); 29% = 1 – (8 + 1594 – 409)/(162 + 1816 – 287). I ignored denominators as they are similar between groups.

翻译如下，徽剑用红字标出核心点：

Peter Doshi：辉瑞和摩德纳的 "95%有效 "疫苗--我们需要更多的细节和原始数据。

2021年1月4日

五周前，当我对辉瑞公司和Moderna公司的covid-19疫苗试验结果提出质疑时，公开的只有研究方案和几篇新闻稿。如今，在FDA对每家公司的mRNA疫苗进行紧急授权之前，由FDA提交并向FDA提交的多份报告中，有两份期刊出版物和约400页的总结数据。虽然一些额外的细节是令人放心的，但有些并不是。在此，我概述了对报告的疗效结果的可信度和意义的新担忧。

"疑似covid-19"

所有的注意力都集中在戏剧性的疗效结果上。辉瑞公司报告了170例PCR确诊的covid-19病例，疫苗组和安慰剂组之间的比例为8比162。但这些数字在一类被称为 "疑似covid-19 "的疾病中相形见绌--那些有症状的covid-19没有被PCR证实。根据FDA关于辉瑞疫苗的报告，"在总体研究人群中，共有3410例疑似但未确诊的covid-19病例，1594例发生在疫苗组与安慰剂组的1816例。"

疑似病例是确诊病例的20倍，不能因为没有PCR检测结果阳性就忽视这一类疾病。事实上这就更迫切需要了解。粗略估计疫苗对出现covid-19症状的疗效，无论是否有阳性PCR检测结果，相对风险都会降低19%（见脚注）--远低于监管机构设定的50%的授权有效性门槛。即使剔除了接种疫苗后7天内发生的病例（辉瑞疫苗409例，安慰剂287例），其中应包括大部分因短期疫苗反应原性引起的症状，疫苗的有效性仍然很低：29%（见脚注）。

如果这些疑似病例中的许多或大多数是PCR检测结果为假阴性的人，这将大大降低疫苗的疗效。但考虑到流感类疾病总是有无数的病因--鼻病毒、流感病毒、其他冠状病毒、腺病毒、呼吸道合胞病毒等--部分或许多疑似covid-19病例可能是由不同的致病菌引起的。

但为什么病因学要重要呢？如果经历 "疑似covid-19 "的人与确诊covid-19的临床过程基本相同，那么 "疑似加确诊covid-19 "可能是比单纯的确诊covid-19更有临床意义的终点。

然而，如果确诊covid-19平均比疑似covid-19更严重，我们还是要记住，归根结底，重要的不是平均的临床严重程度，而是影响住院率的严重疾病的发生率。由于疑似covid-19的人数是确诊covid-19的20倍，而且试验并不是为了评估疫苗是否能阻断病毒传播，因此，无论病原体如何，对严重疾病的分析--也就是试验参与者的住院率、ICU病例和死亡人数--似乎是有必要的，也是评估疫苗是否真正有能力消除疫情的唯一途径。

显然需要数据来回答这些问题，但辉瑞公司92页的报告并没有提到3410例 "疑似covid-19 "病例。其在《新英格兰医学杂志》上的发表也没有。也没有任何关于Moderna疫苗的报道。唯一出现报道的来源是FDA对辉瑞疫苗的审查。

被排除在辉瑞疫苗疗效分析之外的371人。

我们需要更多数据的另一个原因是分析FDA审查辉瑞疫苗的表格中发现的一个未解释的细节。371人被排除在疗效分析之外，原因是 "在剂量2后7天或之前出现重要的方案偏差"。令人关注的是，这些被排除的个体数量在随机组之间的不平衡。疫苗组311人，安慰剂组60人。相比之下，在Moderna的试验中，仅有36名参与者因 "主要协议偏差 "而被排除在疗效分析之外--12名疫苗组vs24名安慰剂组）。

在辉瑞的研究中，这些协议偏差是什么，为什么疫苗组的参与者被排除了5倍？FDA的报告没有说，这些排除物甚至很难在辉瑞的报告和期刊上发现。

发热和止痛药、不盲目和主要事件裁决委员会。

上个月，我对治疗症状的止痛和发烧药物的潜在混淆作用表示关切。我提出，这些药物可能掩盖症状，导致covid-19病例检测不足，可能在为预防或治疗不良事件而接种疫苗的人中数量更多。然而，它们混淆结果的可能性似乎相当有限：虽然结果显示，这些药物在疫苗与安慰剂接受者中的服用频率约为3-4倍（至少辉瑞公司的疫苗-Moderna没有报告得那么清楚），但它们的使用大概集中在使用疫苗后的第一周，是为了缓解注射后局部和全身不良事件而服用的。但累计发生率曲线表明，随着时间的推移，covid-19病例的确诊率相当稳定，症状发生日期远远超过用药后一周。

尽管如此，疫苗组较高的用药率进一步提供了担心非官方解盲的理由。鉴于疫苗的反应原性，很难想象参与者和研究人员无法对他们在哪一组进行有根据的猜测。试验中的主要终点是相对主观的，因此非盲目性是一个重要的问题。然而，无论是FDA还是各公司似乎都没有正式探究过盲法程序的可靠性，以及其对报告结果的影响。

我们对统计covid-19病例的主要事件裁决委员会的程序也不够了解。他们是否对接种疫苗后第一周的抗体数据和患者症状信息进行了致盲？他们采用了什么标准，为什么在由患者报告的结果（covid-19症状）和PCR检测结果组成的主要事件中，这样的委员会还有必要吗？了解这些委员会的成员是谁也很重要。虽然Moderna已经指定了它的四人裁决委员会--都是大学附属的医生--辉瑞的协议说有三名辉瑞的员工做了这项工作。是的，辉瑞的员工。

已有covid的人的疫苗疗效？

已知有SARS-CoV-2感染史或以前被诊断为科维德-19的人被排除在Moderna和辉瑞的试验之外。但仍有1125名（3.0%）和675名（2.2%）辉瑞和Moderna的试验参与者分别被认为基线时SARS-CoV-2阳性。

疫苗在这些受试者中的安全性和有效性并没有得到太多的关注，但由于许多国家的人口中越来越多的人可能是 "后科维德"，这些数据似乎很重要--更何况美国CDC建议 "无论之前是否有症状的SARS-CoV-2感染史 "都要提供疫苗。这是继该机构对辉瑞公司的疫苗得出的结论，即该疫苗对既往有SARS-CoV-2感染史的人有≥92%的疗效和 "无特殊的安全性问题"。

据我统计，辉瑞公司显然报告了8例基线SARS-CoV-2阳性者确诊的、有症状的Covid-19病例（疫苗组1例，安慰剂组7例，使用表9和表10的差异），Moderna，1例（安慰剂组；表12）。

但全球仅有4～31例左右的再感染记录，在数万人的试验中，中位随访时间为2个月，基线时SARS-CoV-2感染者中怎么会有9例确诊的covid-19？这是否如CDC似乎认可的那样，代表了有意义的疫苗疗效？或者可能是别的什么，比如预防covid-19症状，可能是通过疫苗或使用抑制症状的药物，而与再感染无关？

我们需要原始数据

要解决关于这些试验的许多未决问题，需要获得原始试验数据。但目前似乎没有公司与任何第三方共享数据。

辉瑞公司表示，它正在 "应要求提供数据，并接受审查"。这远远没有达到公开数据的目的，但至少留下了一扇门。有多开放还不清楚，因为研究方案说辉瑞公司将在研究完成24个月后才开始提供数据。

Moderna的数据共享声明指出，数据 "一旦试验完成，可应要求提供"。这意味着在2022年中后期的某个时候，因为后续计划为2年。

牛津/阿斯利康疫苗的情况可能没有什么不同，它承诺 "在试验完成后 "提供患者级别的数据。而俄罗斯Sputnik V疫苗的ClinicalTrials.gov条目称，没有计划分享个体参与者数据。

不过，欧洲药品管理局和加拿大卫生部可能会更早地分享任何授权疫苗的数据。欧洲药品管理局已经承诺 "在适当的时候 "在其网站上公布辉瑞公司提交的数据，加拿大卫生部也是如此。

BMJ副编辑Peter Doshi

竞争性利益。我一直在追求疫苗试验方案的公开发布，并共同签署了公开信，呼吁covid-19疫苗相关决策的独立性和透明度。

脚注

本文的计算方法如下。19% = 1 – (8+1594)/(162+1816); 29% = 1 – (8 + 1594 – 409)/(162 + 1816 – 287). 我忽略了分母，因为各组之间的分母相似。

这篇文章下面的评论：

Thank you Peter Doshi. Finally, a serious scientist has carefully evaluated the vaccine data and discovers some serious impropiety, inadequate transparency on these Covid vaccines, and a shocking observation of reduced efficacy to only 19%. Because these vaccines were granted "emergency exemption," these studies should be fully transparent, and yet, Dr. Doshi shows that this is simply not true. Even worse is his discovery that the Pfizer vaccine's results were adjudicated by three Pfizer employees, not independent university-affiliated physicians as the Moderna vaccine was. And the fact that in the Pfizer vaccine trial, 7 subjects in the placebo and only 1 subject in the vaccine group tested positive for Covid-19 at baseline, thereby "stacking the deck."

As Lucy (of "I Love Lucy" fame) was known to say to Ricky, "You've got some 'xplain' to do!"

谢谢彼得-多希。最后，一位严肃的科学家仔细评估了疫苗数据，并发现了一些严重的不当之处，这些Covid疫苗的透明度不足，以及一个令人震惊的观察结果，即疗效降低到只有19%。由于这些疫苗获得了 "紧急豁免"，这些研究应该是完全透明的，然而，Doshi博士表明，事实根本不是这样。更糟糕的是，他发现辉瑞疫苗的结果是由三名辉瑞公司的员工判定的，而不是像摩德纳疫苗那样由独立的大学附属医生判定的。而在辉瑞疫苗试验中，安慰剂组有7名受试者，而疫苗组只有1名受试者在基线上检测出Covid-19阳性，从而 "叠加"。

正如Lucy（《我爱Lucy》的名角）对Ricky说的那样，"你要做一些'解释'！"

Thanks so much for exposing some of the slippery statistical issues around the vaccine trials. I would add one more problem: no measure of exposure level. Specifically, adverse effects after both 1st and 2nd dose, even if mild, might have kept participants in the vaccine arm at home/less active (thus, exposed) on average a few more days than placebo recipients. Considering the short observation window after 2nd dose (just a few weeks) available so far, one cannot rule out that this difference might have had an impact on infection rate. In any instance, I think at least some gross or surrogate data reflecting the level of exposure (e.g. population size in city of residence, n° of people in household, average interactions at work, use of public transport...) should have been included in all the studies. Intensity of exposure is more important than other factors that were carefully balanced between arms.

As already expressed by others, more than worried about adverse effects, I am thus far not very excited about efficacy data. Plus, when we the translate this to real world scenarios effectiveness will probably be lower. Need more data.

Disclosures: I have no COI; am definitely all pro-vaccines, but only if worthwhile.

非常感谢你揭露了围绕疫苗试验的一些棘手的统计问题。我想再补充一个问题：没有测量暴露水平。具体来说，第1次和第2次剂量后的不良反应，即使是轻微的，也可能使疫苗组的参与者在家/不活跃（因此，暴露）平均比安慰剂接受者多几天。考虑到目前第2次剂量后的观察窗较短（仅几周），不能排除这种差异可能对感染率产生影响。在任何情况下，我认为所有的研究都应该至少包括一些反映暴露水平的总数据或代用数据（例如居住城市的人口数量、家庭人口数、工作中的平均互动、使用公共交通工具......）。暴露强度比其他因素更重要，这些因素在不同的武器之间得到了仔细的平衡。

正如其他人已经表达的那样，比起担心不良反应，我到目前为止对疗效数据不是很兴奋。另外，当我们把这个转化为现实世界的场景时，有效性可能会更低。需要更多的数据

披露。我没有COI; 绝对是所有支持疫苗， 但只有当值得。

While I perfectly agree that we need full data release for those trials, I find it strange that he only mentions the Oxford/AZ in passing, for which much less and much more disconcerting data is published, changing after the political need and pandemic situation. For the less effective (62%) Oxford vaccine with half the number of participants (is also if vaccinated volunteers), 87% were under 55, and similar percentages were white, all healthy, and there is no data, how effective this vaccine is in over 65s. The others have a proven efficacy in older people. So, why you vaccinate over 70s with the vaccine with no data for its efficacy for that age group and make unsubstantiated claims that they are 70% protected after one dose for at least 12 weeks suggests that price, supply and logistics are the main criteria for the choice, NOT the protection of the vulnerable from severe disease or death. We need proper publication of all trials and the dosage/timing regime, which has turned out most effective.

虽然我完全同意我们需要全面公布这些试验的数据，但我觉得很奇怪，他只顺便提到了牛津/AZ，对于这些试验，公布的数据要少得多，也多得多，令人不安，在政治需要和疫情之后，就会发生变化。对于效果较差（62%）的牛津疫苗，参与人数只有一半（也是如果接种志愿者），87%的人在55岁以下，类似比例的人都是白人，都是健康人，没有数据，这种疫苗在65岁以上的人中效果如何。其他的对老年人有疗效。所以，为什么你给70岁以上的老年人接种疫苗，却没有数据显示其对该年龄组的疗效，并毫无根据地声称他们在接种一剂疫苗至少12周后就能得到70%的保护，这说明价格、供应和物流是选择疫苗的主要标准，而不是保护弱势群体免受严重疾病或死亡的伤害。我们需要适当公布所有试验和剂量/时间制度，哪种制度最有效。

This does not really surprise me at all. I never believed the ambitious efficacy hype and claims these vaccines have. The phase III trials were never designed to demonstrate they save lives, improve health outcomes, reduce admissions. We still are in the dark on whether they can prevent transmission of the Sars-cov-2 virus, how long immunity lasts if at all and what are the short term and long term unintended adverse effects which will take up to 20 years to determine. Already there have been 9 adverse reactions to the Pfizer vaccine. Seven in US and two in UK, these included anaphylaxis, Bell's Palsy and some other issue.

In UK the MHRA has only granted them temporary approval for a year, not full marketing approval, under EC 174 of the Human Medicines Regulations 2012. This implies they will be withdrawn if problems emerge. In any case they have to resubmit for approval when the temporary approval expires.

The Oxford Astra Zeneca vaccine is a viral vector type with a gene added, effectively they are injecting a GMO. Again long term effects are unknown, what will happen if the gene codes for something other than spike protein, or the vector causes issues. Time will tell. Personally I do not fancy having either an mRNA or a GMO vaccine. A protein subunit one light be less risky.

这其实一点也不令我吃惊。我从不相信这些疫苗的雄心勃勃的疗效炒作和宣称。三期试验的目的从来就不是为了证明它们能拯救生命，改善健康状况，减少住院人数。我们仍然是在黑暗中，他们是否可以防止Sars-cov-2病毒的传播，多长时间的免疫力持续，如果在所有和什么是短期和长期的非预期的不良反应，这将需要长达20年的确定。目前已经有9起辉瑞疫苗的不良反应。7起在美国，2起在英国，这些包括过敏性休克、贝尔麻痹症和其他一些问题。

在英国，MHRA根据《2012年人类药品条例》EC174的规定，只给了他们一年的临时批准，而不是全面上市批准。这意味着如果出现问题，他们将被撤回。在任何情况下，他们必须在临时批准到期后重新提交批准。

牛津阿斯利康疫苗是一种添加了基因的病毒载体类型，实际上他们是在注射一种转基因生物。同样长期的影响也是未知的，如果基因编码的不是尖峰蛋白，或者载体导致问题，会发生什么。时间会证明这一点。我个人不幻想有任一 mRNA 或 GMO 疫苗。一个蛋白质亚单位一光是较少的风险。

Why were both of these trials "observer-blinded", and not double-blinded? There is no explanation in the texts. There are no obvious descriptions of the nature of interactions between patients and clinicians. By "observer"-blinded, does that mean the patients were unblinded?

 Whether they were or not, unblinding of both parties should be anticipated. Unblinding could have many consequences. For example, does a clinician get lazy about PCR testing if they think the symptoms are due to a recent injection that wasn't a placebo? Does a patient even bother consulting a clinician if they think their symptoms are from a vaccine? And could the exact opposites be true if patients/clinicians suspect they got a placebo? Could "testing fatigue" occur? By that, I mean could a negative PCR following vaccine-caused symptoms lead to less likelihood of running a PCR 2 weeks later when real disease symptoms emerge?

 Why was testing left up to clinician judgement? Do the clinicians have any ties to the pharmaceutical companies?

 There is not enough info on dropouts. What a patient says and what an observer records are not always the same thing. Can we trust that so many dropouts were for the innocuous reason of "withdrawing consent"? Are cases of illness or reactions being unreported in some dropouts? It is common that when patients abandon a treatment, they simply don't follow up

The Moderna study cited 30 severe cases occurring from 14 days after the second dose. They had more than 14,000 people in each group. This is at odds with the Pfizer data which says only 5 total cases occurred from 7 days after second dose. This means Pfizer had longer to observe cases, plus their group size was nearly 22,000. This discrepancy needs explaining. Is this just random chance, or something else? Extrapolating from Moderna's count, under simple expectation, one would expect more like 70 cases to be reported by Pfizer, not five.

 What is going to happen months or years down the line if boosters are needed? Could pathogenic priming start becoming apparent at such a later date?

In the Moderna supplements, there seems like a possible signal for grade 4 events, but what such events are is not clearly defined.

 Will we be promoting new vaccines to people who have already had COVID but don't know it?

So to recap...We have clinical trials with subjective outcomes, patients and clinicians who are likely unblinded, outcome measures that aren't the ones we really care about, and in any case the vast majority of suspected cases are excluded from primary analysis, and to top it off the raw data is not available? Personally, it is hard for me to fathom that the existing published studies at 2 months are of any value whatsoever.

为什么这两项试验都是 "观察者盲"，而不是双盲？文中没有解释。对患者和临床医生之间的互动性质没有明显的描述。所谓 "观察者"-盲，是否意味着患者没有被盲？

 不管他们是否是，双方的不盲目应该是预料之中的。解盲可能会产生很多后果。例如，如果临床医生认为症状是由于最近注射了不是安慰剂的针剂而引起的，是否会懒得做PCR检测？如果患者认为自己的症状是由于疫苗引起的，是否还会去咨询临床医生？而如果患者/临床医生怀疑自己注射了安慰剂，是否会出现完全相反的情况？是否会出现 "测试疲劳"？我的意思是，在疫苗引起的症状后PCR呈阴性，是否会导致2周后真正的疾病症状出现时运行PCR的可能性降低？

 为什么检测要由临床医生来判断？临床医生与制药公司有什么关系吗？

 关于辍学的信息不够。病人说的和观察者记录的不一定是一回事。我们能相信这么多的退出是出于 "撤回同意 "的无害原因吗？在一些退学者中，是否有疾病或反应的病例未被报告？常见的情况是，当患者放弃治疗时，他们根本就没有进行后续治疗

Moderna的研究引用了30个严重病例，这些病例发生在第二次服药后14天。他们每组有超过14000人。这与辉瑞公司的数据不一致，辉瑞公司的数据说，从第二次用药后7天开始，总共只有5个病例发生。这意味着辉瑞有更长的时间来观察病例，再加上他们的组数接近22000人。这种差异需要解释。这究竟是随机的偶然，还是其他原因？根据Moderna的统计推断，在简单的预期下，人们会期望辉瑞报告的病例更像是70例，而不是5例。

 如果需要增效剂，几个月或几年后会发生什么？会不会在这么晚的时候，病原体引流开始变得明显？

在莫德纳补充剂中，似乎有可能出现4级事件的信号，但这种事件是什么并没有明确定义。

 我们会不会向已经得过COVID但不知道的人推广新疫苗？

所以总结一下......我们的临床试验有主观的结果，患者和临床医生很可能是不盲目的，结果衡量标准不是我们真正关心的，而且无论如何，绝大多数疑似病例都被排除在初级分析之外，最重要的是原始数据无法获得？就我个人而言，我很难理解现有发表的2个月的研究有什么价值。

因为我不是生物学方面的专业人员，只能做简单翻译，而且对于评论里面生物学专业性的内容也一知半解。但是我的数学专业知识，让我看明白了统计数据部分的问题。很明显，这不是真正的双盲实验，而是人为“美化”数据的东西。

希望我的读者中有专业人员，看看这篇评论还有哪些关键点。

不过从目前看到的评论内容来看，基本上一边倒支持原评论人