Several researchers in Xiangya Hospital have previously made unremitting efforts to use the same batch of data of new crown patients hospitalized in Xiangya, left ratio, right ratio, and issued three papers to demonstrate that azvudine is effective in new crown hospitalized patients, not only effective, but also more effective than P drugs.
When we examined the data, we found that the data of the same set of patients had many contradictions in several papers, making the reliability of these studies quite dubious (suspected fraud!). Tear off the skin that Azvudine works in the real world).
On July 5, 2023, researchers from Beijing You'an Hospital posted a newsletter in J Med Virol, one of the journals in the Xiangya Hospital series, questioning the so-called effectiveness of azvudine in the real world:
In this question, the researchers of Youan Hospital first mentioned the basic principle: new crown antiviral drugs need to be used in the early stage of the disease, generally within 5 days of symptomatic or confirmed infection. In the Xiangya Hospital study, about 90% of inpatients exceeded this optimal intervention window. The vast majority of patients are not in the treatment window, and the so-called effectiveness can be observed, which is too strange.
To note a little here, the Xiangya Hospital research team published a past article on J Med Virol that determined that in hospitalized patients, the effectiveness of Aziv is higher than that of P drugs. Therefore, the communication of Youan Hospital is also aimed at the article that azvudine is superior to P drugs:
Coincidentally, researchers at Youan Hospital have also done real-world studies of azvudine before, and found that the nucleic acid conversion time with azvudine is significantly longer than that of patients who use P drugs. The nucleic acid conversion time reflects the performance of inhibiting the virus, that is, the anti-new coronavirus effect of azvudine may be significantly weaker than that of P drugs. An antiviral drug, obviously the antiviral effect is weaker, but the "effectiveness" is better, which is very bizarre.
We have also pointed out before that from the published literature, the ability of azvudine to inhibit the new crown virus is very weak, and the metabolic distribution is concentrated in the thymus, rather than the lung of the target organ of the new crown virus, making its anti-new crown effect very suspicious. Researchers at Youan Hospital also raised these doubts and made detailed calculations.
They pointed out that in HIV clinical trials, patients took 2 mg of azvudine orally twice a day for seven days, and the peak blood concentration was 1.95-2.17 ng/ml, and if it was 4 mg orally once a day, the peak blood concentration was 4.41-3.48 ng/ml (don't ask me what concentration range is written from high to low, this is the original text of the azvudine instructions). Azvudine inhibits EC50 (half of the inhibitory effect) of the new coronavirus in vitro, which is converted to 343.46ng/ml according to the literature. The dose of azvudine for new crown treatment is 5mg per day, from the perspective of drug metabolism, the blood concentration that can be achieved at this dose is 108,000 miles away from EC50 that inhibits the new crown virus in vitro experiments, how to fight the virus?
These doubts are based on the basic principle of action of antiviral drugs, and the use of azvudine public data is relatively fair. However, the Xiangya Hospital team also adhered to the excellent tradition of writing papers quickly in the past, worked hard to write a book, and published a reply to the You'an Hospital team's questions on the same day:
You look at this title: Take the data and don't guess to evaluate the clinical effectiveness of azvudine, this breath, swallow mountains and rivers.
However, is the most basic drug metabolic distribution data data? Is the data on the inhibitory efficiency of antivirals data?
Looking at the content of the reply, I found that in the eyes of the Azvudine new crown treatment expert group composed of four dermatologists in Xiangya, the above is really not data, at least not the data they can see:
Let me give you a translation: as a clinician, drug experiments, pharmacokinetics or something, we have limited understanding, there is a problem with azvudine in this regard, you go to the people who do those studies.
The latter paragraph is more blunt:
Translate this paragraph on a blue background: Children, evaluating drug effectiveness depends on clinical data, and cannot be based on a few basic research papers to piece together speculation. The antiviral effect of remdesivir can be given later, but it is not effective in patients on a ventilator, and the example of metformin in the treatment of long new crowns.
To be able to write this kind of content, we can only mean:
First of all, the drug metabolism distribution and the EC50 that inhibits the virus are very important data, and the drug metabolism data of azvudine is also data in clinical trials, saying that these doubts are patchwork basic research, and I don't know how to define basic research.
An effective drug necessarily requires the delivery of an active drug molecule to the targeted tissues and organs. Azvudine inhibits the new crown virus weakly in vitro, which means that the activity of this molecule against the new crown is weak. Blood levels are low and there is no drug enrichment in the lungs, meaning that azvudine is also not delivered to the targeted tissue.
Is such an important data ignored by a sentence of basic research? From the perspective of drug research and development, early clinical trials are the need to evaluate drug metabolism and pharmacodynamic power, such as a new crown antiviral drug, that is, to see how much blood concentration, lung tissue concentration can be, whether it can inhibit the virus to the level required, can see the decline in toxic load, based on these to decide whether it is worth carrying out large-scale clinical trials to confirm the effectiveness of reducing the risk of severe disease, for example.
Even the drug activity and metabolic distribution do not meet the basic criteria for the effectiveness of antiviral drugs, and what to say from clinical data to see the effectiveness is not called conducting meaningful clinical research, which is called making patients or subjects bear unnecessary risks. It is a violation of basic medical biological ethics, called Kusanagi human life.
Secondly, clinical validity data is very important, but it also depends on the reliability of relevant research. Several dermatologists at Xiangya also acknowledged that their real-world study was a single-center retrospective analysis with various possibilities for bias. Emphasizing that this is clinical effectiveness data, so higher than the question based on "basic research" is inevitably a banner of tiger skin.
As far as Xiangya and these people published a series of "Azvudine thief effective" papers, we really have to doubt the reliability of their data.
In this regard, the You'an Hospital team did not mention it, but several dermatologists in Xiangya wrote this paragraph without knowing how:
The effect is: we heard that some readers questioned the data in the patient screening in Figure 1 in our masterpiece, we have a repeat number here, and each patient will write it if they meet a standard. This is probably in response to the number of all patients in the Azvudine vs. P comparison paper, the number of patients in the patient screening chart together exceeds the initial 2118 - a point I questioned in my previous article.
Speaking of which, I strongly suspect that this paragraph was written in response to my public account article, after all, I haven't seen much discussion of this issue. Just as a pharmaceutical company in Henan reported to WeChat that my article needs to be discussed, this kind of feedback makes this small citizen feel honored.
It's just that I'm quite curious, as I mentioned in my last analysis of Xiangya's batch of "Azvudine Thief Effective" papers, the three papers written by the same group of people have very similar compositions for patient screening, and some of the numbers together are exactly 2118 total hospitalizations, obviously there is no double counting; Some are excessive, now it is said to be a repeat number, do you still randomly change the style to write papers? It's interesting enough.
In addition, I also pointed out in my previous public account article that such double counting theory cannot explain the contradictions in the data of several papers. In the paper that azvudine was shown to be effective compared to no drugs in patients with underlying medical conditions, there were 245 users of azvudine with underlying medical conditions:
In the first table in the comparison paper between azvudine and P drugs that was questioned by Xiangya's team this time, it shows that 253 patients with a history of underlying diseases using azvudine are used:
Not right at all!
Xiangya's team inexplicably added a sentence in its reply: "Pregnant women are mistakenly classified as patients with underlying diseases." I don't know if I want to respond to the question that the number of underlying diseases in the two articles is not right.
However, given the specific content of the paper, this statement is also extremely dubious. Because the paper gives the corresponding number of people for various underlying diseases:
If I were to say, what pregnant women are misclassified is that there is no silver here and here 300 taels. The various underlying diseases in the table, from high blood pressure to cancer, are listed, that is, there is no pregnancy column, how can pregnant women be misclassified? Which underlying disease is it classified in? Are all pregnant women with high blood pressure, or diabetes, or cancer?
According to several authors, when constructing an analysis group with similar characteristics in the end, pregnant women happened to be excluded, so the final conclusion was not affected and still reliable. How is it a coincidence that Xiangya these dermatologists have met ah? Why not buy lottery tickets? How about going to Henan to buy two real lottery tickets?
Even if we believe that you inexplicably appear several pregnant women who are not mentioned in a word in three papers, solving the problem of inconsistency in the number of azvudine users compared to no drug, and the paper comparing azvudine to P drug, and the number of users of azvudine with underlying diseases.
As I pointed out last time, in the paper comparing azvudine to no drug, 245 users of azvudine with underlying conditions had 17 disease progressions and 5 died:
Later, in Xiangya's paper responding to You'an Hospital's Azvudine nucleic acid conversion slower than P drug, only 16 of the 245 Azvudine users with underlying diseases progressed and 4 died:
What's going on here? And where did several dermatologists make a classification error that does not affect the conclusion? How about a few of you to think about it again, carefully think about how to make up numbers and make up a decent story?
The Youan Hospital team mentioned at the end of the article questioning whether Azvudine is really a miracle medicine:
After the first wave of the epidemic, now that many targets have been verified in China and the new crown antiviral drugs that have shown stronger antiviral effects have been approved, and the drug shortage has been solved, it is time for new crown patients to get more effective drugs.
Indeed, during the pandemic, the FDA approved several drugs through emergency use authorizations. But now that the new crown no longer constitutes a public health crisis, and even in China, it has returned to the routine management method of Class B and B pipe, which requires a re-examination of various drugs that are still alive in an emergency.
They should no longer continue to carry on emergency signboards and earn money from ordinary people who have begun to live a normal life. Even the dermatologists in Xiangya said that the clinical research of azvudine is limited. Drugs with limited evidence should not use emergency use authorizations in response to public health crises to mask their lack of data.
"Drugs" without sufficient efficacy data, or even "drugs" with sufficient reason to doubt their reliability and safety, were originally urgently authorized, and now there is a need for an "emergency" removal mechanism to remedy them.