Researchers of You'an Hospital questioned the real world research of Xiangya: is Azvudine really a magic drug?

Previously, several researchers from Xiangya Hospital made unremitting efforts to use the data of the same group of COVID-19 patients hospitalized in Xiangya, left to right, and issued three papers to demonstrate that Azvudine is effective in COVID-19 patients, not only effective, but also more effective than P drug.When we tested the data, we found that the data of the same group of patients were contradictory in several papers, which made the reliability of these studies quite suspicious (suspected fraud! Tear off the mask of Azvudine's effectiveness in the real world)

Previously, several researchers from Xiangya Hospital made unremitting efforts to use the data of the same group of COVID-19 patients hospitalized in Xiangya, left to right, and issued three papers to demonstrate that Azvudine is effective in COVID-19 patients, not only effective, but also more effective than P drug.

When we tested the data, we found that the data of the same group of patients were contradictory in several papers, which made the reliability of these studies quite suspicious (suspected fraud! Tear off the mask of Azvudine's effectiveness in the real world).

In fact, we are far from alone in questioning the miraculous effects of Azvudine. On July 5, 2023, researchers from Beijing You'an Hospital published a newsletter on JMedVirol, one of the journals of Xiangya Hospital's series of papers, questioning the theory that Azvudine is effective in the real world:

In this query, researchers from You'an Hospital first proposed the basic principle: COVID-19 Antiviral drug should be used in the early stage of disease, usually within 5 days after symptoms or confirmed infection. In the study of Xiangya Hospital, approximately 90% of hospitalized patients exceeded this optimal intervention window. The vast majority of patients are not in the treatment window and can still observe the so-called effectiveness, which is somewhat strange.

Here is a slight annotation. The research team of Xiangya Hospital has previously published articles on JMedVirol, targeting hospitalized patients, and the efficacy of Aziv is higher than that of P-drug. Therefore, the communication of You'an Hospital is also aimed at the article that Azvudine is better than P medicine:

Coincidentally, researchers from You'an Hospital have also done real world research on Azvudine before, and found that compared with patients using drug P, the nucleic acid negative time of patients using Azvudine was significantly longer. The time when nucleic acid turns negative reflects the performance of inhibiting the virus, that is to say,The anti COVID-19 effect of Azvudine may be significantly weaker than that of P drug. It is very strange that an antiviral drug, although having weaker antiviral effects, has better "effectiveness".

We have also pointed out before that, according to the published literature, Azvudine's ability to inhibit COVID-19 is very weak, and its metabolic distribution is concentrated in the thymus, rather than the lung, the target organ infected by COVID-19, making its anti COVID-19 effect very suspicious. Researchers from You'an Hospital have also raised these doubts and conducted detailed calculations.

They pointed out that in HIV clinical trials, patients took 2 mg of Azvudine twice a day for seven consecutive days, and the peak blood concentration was 1.95-2.17ng/ml. If they took 4 mg once a day, the peak blood concentration was4.41-3.48ng/ml(Don't ask me what concentration range is written from high to low. This is the original text of Azvudine instructions.). But the EC50 (half inhibition) of Azvudine against COVID-19 in vitro is343.46ng/ml. The dose of Azvudine for COVID-19 treatment is 5mg per day. From the perspective of Drug metabolism, the blood concentration that can be reached by this dose is far from the EC50 of COVID-19 inhibition in vitro experiments. How can we fight the virus?

These doubts are based on the basic principle of antiviral drugs, and the data published by Azvudine are fairly used. However, the Xiangya Hospital team also adhered to the excellent tradition of writing papers with great speed in the past, and wrote with great effort. On the same day, they published a response to the questions raised by the You'an Hospital team:

Take a look at the title:Evaluate the clinical effectiveness of Azvudine with data rather than speculationThis tone is overwhelming.

But is the most basic Drug metabolism distribution data? Is the data on the virus inhibition efficiency of antiviral drugs data?

Upon reading the reply, I found that it is located in XiangyaAzvudine COVID-19 treatment expert group composed of four dermatologistsIn my opinion, the above is not really data, at least not data that they can see:

As a clinician, I have limited knowledge about drug experiments and pharmacokinetics. There is a problem with Azvudine in this regard. Go to find the people who do the research.

The following paragraph becomes even more straightforward:

Translate the blue background and draw this paragraph: Children, evaluating the effectiveness of drugs depends on clinical data, not just a few basic research papers pieced together to speculate. Later, examples of remdesivir's antiviral effect is good, but it is ineffective in patients on ventilator, and Metformin's treatment of Changxinguan were also cited.

To be able to write such content, we can only express:

First of all, the distribution of Drug metabolism and the EC50 of virus inhibition are very important data, and the data of Azvudine's Drug metabolism are also data in clinical trials. It is said that these doubts are a patchwork of basic research, and we do not know how to define basic research.

An effective drug necessarily requires delivering an active drug molecule to targeted tissues and organs. Azvudine has a weak inhibition of COVID-19 in vitro, which means that the molecular activity against COVID-19 is weak. The blood concentration is very low, and there is no drug enrichment in the lungs, which means that Azvudine has not been delivered to targeted tissues.

Is such important data ignored in a basic research sentence? From the perspective of Drug development, early clinical trials need to assess Drug metabolism and pharmacodynamics. For example, a COVID-19 antiviral drug is to see how much the blood concentration and lung tissue concentration can reach, whether they can reach the level required to inhibit the virus, and whether they can see the decline of viral load. These are the basis for determining whether large-scale clinical trials are worthwhile to confirm the effectiveness of reducing the risk of severe diseases.

Even drug activity and metabolic distribution do not meet the basic standards for antiviral drug efficacy. When it comes to evaluating efficacy from clinical data, it is not called conducting meaningful clinical research, but rather placing unnecessary risks on patients or participants. It violates the basic ethics of medical biology and is called reckless disregard for human life.

Secondly, clinical efficacy data is important, but it also depends onThe reliability of relevant research. Several dermatologists from Xiangya also admitted that their real world research is only a single center retrospective analysis, with various possibilities of bias. Emphasizing that this is clinical validity data, therefore it is higher than the doubts raised based on "basic research", and may be considered a big banner of pulling the tiger's skin.

I really doubt the reliability of their data in the series of papers "Azvudine is effective" published by Xiangya.

In this regard, the team of You'an Hospital did not mention that several dermatologists from Xiangya had somehow written this paragraph:

The main idea is: I heard that some readers have questioned the data in the patient screening section of Figure 1 in our work. Here, we have duplicate numbers, and each patient who meets a standard will be written in. This is probably in response to the fact that the total number of all patients in the patient screening chart in the paper on the comparison of Azvudine and P drugs exceeds the initial 2118 people - which is also a point I questioned in the previous article.

Speaking of which, I strongly doubt that this paragraph was written for my official account article. After all, few people have seen this discussed. Just like a pharmaceutical company in Henan reporting to WeChat that my article needs to be discussed, this kind of feedback makes me, as an ordinary person, deeply honored.

But I'm curious. As I mentioned in my last analysis of Xiangya's "Azvudine thieves are effective" papers, the three papers written by the same group of people have very similar composition for screening patients. Some of them add up to exactly 2118 total inpatients, obviously without repeated counting; Some of them are beyond the limit. Now, when it comes to repetition numbers, do you still write papers in a different style at random? It's really interesting.

In addition, I pointed out in the previous official account article that this kind of repeated counting theory can not explain the various contradictions in the data of several papers. Among patients with basic diseases, Azvudine is more effective than that without drugs. In the paper, Azvudine users with basic diseases are245 people:

However, the first table in the paper on the comparison between Azvudine and P drug, which was questioned by the Xiangya team, showed that the patients with basic disease history who used Azvudine were253 people:

Not at all!

The Xiangya team inexplicably added a sentence in the reply, "Pregnant women were mistakenly classified as patients with underlying diseases. I don't know if I want to respond to the issue of the number of basic diseases not matching in the two articles.

.:

If you ask me, what is the wrong classification of pregnant women? It's actually that there is no silver in this area, three hundred taels. The various basic diseases in the table, from hypertension to cancer, are clearly listed, except for the absence of pregnancy column,Why are pregnant women misclassified? Which underlying disease has it been classified into? Are all pregnant women suffering from hypertension, diabetes or cancer?

1:1.Why are all these dermatologists from Xiangya encountering any coincidences?Why not buy lottery tickets? How about going to Henan to buy two real lottery tickets?

Even if I believe you somehow, there are several pregnant women who have not mentioned a word in three papers, which solved the problem that the number of users of Azvudine with basic diseases is inconsistent with the papers of no drug ratio, the papers of Azvudine with drug ratio, and the papers of Azvudine with basic diseases.

I also pointed out last time that 245 users of Azvudine with basic diseases appeared in the paper comparing Azvudine with no drugs175:

Later, Xiangya responded to the paper of You'an Hospital that the nucleic acid conversion of Azvudine was slower than that of drug P, which was also among 245 Azvudine users with basic diseases164:

What's going on here?Where did several dermatologists make a classification error that did not affect the conclusion?Could you please think about it again and carefully consider how to gather the numbers and create a decent story?

:

After the first wave of the epidemic, China has now approved COVID-19 antiviral drugs with multiple targets that have been verified and demonstrated stronger antiviral effects, and the problem of drug shortage has been solved,It's time for COVID-19 patients to get more effective drugs.

.Need to re-examine various medications that are still in emergency situations.

..Drugs with limited evidence should not use Emergency Use Authorization to deal with public health crisis to cover up their insufficient data.

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