Who has the final say in the effectiveness of drugs? Radcivir clinical trial super cow science popularization!

The epidemic situation is like a military order At the time of new coronavirus raging in China, many medical researchers and developers are working day and night to find a specific drug to treat new coronavirus pneumonia The public is strongly looking forward to the emergence of the specific drug, so that Shuanghuanglian has been sold out Only drug researchers understand how long a drug's R & D cycle, how difficult it is to verify the effectiveness of a drug, and how little is the chance of success The above characteristics of new drug development are simply contrary to the high explosive and short cycle characteristics of new coronavirus pneumonia The research and development of a drug usually goes through drug screening, animal test and human clinical test, and the clinical test is divided into 1 phase, 2 phase and 3 phase In general, the research and development of a new drug takes 10 years and 1 billion US dollars Therefore, it is impossible to develop a new drug from scratch in a short period of time to fight against new coronavirus pneumonia Therefore, drug researchers are looking for good drugs from those who have been on the market or are more mature in the research of new drugs Fortunately, there is a drug like this: remdesivir from Gilead makes us look forward to it In this paper, we will not talk about drug screening, animal testing, phase 1 and phase 2 clinical trials, let alone safety We will take the phase 3 clinical trials just started by ridcivir as an example to popularize what kind of clinical trials can really prove the effectiveness of a drug We have seen novel coronavirus novel coronavirus mild to moderate pneumonia (308 cases) from two patients in the hospital The first is a new severe acute respiratory syndrome (453 cases) in The two trials are independent of each other, but both of them are randomized, double-blind and controlled clinical trials (see the text with red dot in the figure below) Why do researchers have to "persevere" to carry out such a complex experiment and "waste" precious time in such a critical moment when people are eager to use radceway immediately? No other, only because randomized, double-blind, controlled clinical trial is to verify whether a drug is effective international gold standard This gold standard is like a mirror or monkey king's eyes, which can distinguish whether a drug is effective and return a "magic drug" to its original form The core of the randomized, double-blind and controlled clinical trial is "control" This study is divided into two groups: the experimental group and the control group The experimental group was given 200mg (intravenous drip) of ridcivir on the first day, and the maintenance dose of ridcivir was 100mg every day for 9 days; the control group was given placebo, the same use Why use placebos instead of radcivir? Isn't that a joke about people's life and health? Because there is no control, it's like the sun rises after the rooster crows for 365 days in a row, and it can't prove that the sun is the same as the rooster crows Only when the cock's mouth is covered every time, the sun does not rise, can we preliminarily prove that the sun is called by the cock What is the novel coronavirus pneumonia? If there is no comparison, all new crown pneumonia patients will be given a certain drug Whatever drugs are used, they may get good results in the end, because some patients can heal themselves Most of the patients can also be cured without any specific drugs Therefore, we need as like as two peas in the control test The control is divided into positive control and placebo control The placebo is made of water or starch This experiment is Reed Wei Wei The placebo is water for injection, the shape is exactly the same as the test medicine, but it has no effect Some patients took placebo, some patients took test drug, this test proved its effectiveness by comparing the differences between the two groups Novel coronavirus pneumonia is a common concern on the Internet Many people worry that using a placebo is not ethical and the epidemic is so serious that others will get a new crown pneumonia and save people like fire fighting If we carefully analyze the trial scheme, rational thinking can be relieved: according to the patient's condition, the clinical trial of radcivir can be divided into two trials Patients with mild to moderate pneumonia have mild symptoms and can survive without drugs, so it's OK to use placebo; for patients with severe pneumonia, different strategies are adopted Although placebo is also used, both the control group and the trial group should "combine standard therapy" The placebo group was "standard therapy + placebo", and the experimental group was "standard therapy + ridcivir" Just like the author and Yao Ming stand on the same table, although our height has increased, but we can also distinguish between height and short, so that we can not only do experiments, regardless of life Some people say, that's still trouble Why not use positive control? It's also good for patients The positive control drug should be a proven effective drug There are many effective drugs reported in the news, but none of them have been verified What can be used as a control? In addition, the positive control has its disadvantages and is prone to false-positive (false effectiveness) Therefore, the new drug research advocates using placebo as the control, which will not be carried out here and will be discussed later What are the results that show whether the drug works? No control group was used, or placebo control was used, but the effect of the two groups was similar, even if the cure rate was as high as 90%, it could not show that the drug was effective (Trial 1, trial 2) If there is a significant difference between the two groups (the experimental group is slightly better than the placebo group), even if the cure rate is only 30%, it can also show that the drug is effective (Figure 3 of the experiment) Therefore, the curative effect ratio is relative value, not absolute value There is no control experiment to say that the curative effect is not credible It's not enough to only control, but also "randomly" assign patients to two groups, rather than "randomly" Otherwise, researchers assign light patients or young people to the experimental group, and severe patients or old people to the placebo group Even if there are differences between the two, it doesn't mean it's effective, only that the manufacturer is too bad and the researcher is too stupid The simplest and most primitive random method is to use trial drugs for the first, third, fifth, seventh and ninth patients, and "control drugs" for the second, fourth, sixth, eighth and tenth patients Later, random tables were used, and now statisticians were randomly assigned into groups through professional software But can randomized trials alone avoid deviations from the true value of drug efficacy? Wrong, only random experiments without blind method have major defects, and psychological effects will cause huge deviation to the test results Therefore, we have to invite the expert of double-blind test after "control" and "random" This is a master among the masters, and ordinary people can't afford it, so most of the literature we see and the reports we hear are not double-blind experiments But the requirements of new drug research are very strict What new drugs can we do without money? So the "double-blind test" in new drug research is essential Even if ridcivir is in a hurry, we still invite this "slow doctor" Why is "double blind trial" a slow doctor? In the clinical trial of ridcivir, the main indicators to judge whether a single patient is effective are: from the beginning of treatment (remdesivir or placebo) to fever, respiratory rate, blood oxygen saturation to normal and cough relief, and lasting for at least 72 hours, it can be considered effective Although the longest observation time is 28 days, some people may be effective in a few days If it is not double-blind, we can get the preliminary test results and expand the use You don't see, the results of the online clinical trial have been "out"; you don't see, yesterday a famous host of CCTV asked an expert about the results of the clinical trial At this juncture, I met a slow doctor in a hurry Don't worry, wait for me to come slowly The so-called single blind test is that doctors know, but patients don't know whether they are using drugs or placebos, while double blind test is that patients and doctors don't know, so it's called double blind Does the manufacturer know? Sorry, the manufacturer doesn't know Who knows? Only statisticians involved in this study At the end of the experiment, only after all the experimental data are collected can the statisticians "uncover the blindness" The main researchers know which people are injected with drugs and which people are injected with "water" Therefore, the author is responsible to say that before the end of the clinical trial (officially expected to be April 27), any statement about the efficacy of radcivir is groundless, and the relevant rumors circulated on the Internet are not broken So why do we need to conduct a double-blind experiment, which is time-consuming and money-consuming What's the effect? Mainly to avoid the placebo effect People's subjective factors are very strong For the patients who use the medicine, some people know that they use the "special medicine" before the whole nation They feel refreshed, have increased resistance, have calmed down breathing, and have slowed down coughing (these two are indicators to judge the effectiveness); for the patients who are injected with placebo, they are angry: "the injection of water can work, and the sun can also work from the West So, because of the anger and shortness of breath, cough intensified, and even quit the experiment: "take me as a mouse, and make some water to fool people, I want to quit the experiment!" According to the rules of passage, patients can withdraw unconditionally at any time How can this experiment be carried out? Doctors are also human beings They also have subjective consciousness They pay more attention to the patients who have used the medicine and carefully observe the treatment results They tend to be effective: "a good medicine like radcivir, the hope of treating the new crown, has some effect, at least." For those who took placebo, they didn't pay much attention, and they often gave negative comments on the treatment results Therefore, some studies have shown that the effect may be exaggerated by 30% - 50% in the experiment without blind method In addition to randomization, control and double blindness, a certain sample size is also needed New drug research and development can not be a few or dozens of cases, but a large sample size clinical trial is needed There are 761 cases in two trials of radcivir, which are relatively few Radcivir's clinical trial also mentioned "multicenter research", that is, in addition to China Japan Friendship Hospital as the leading unit, there are many hospitals participating in it In addition to speed up, it is more important to avoid systematic errors in a single hospital How can a drug count as effective? Radcivir's clinical trial program tells us that only through randomized, double-blind, (placebo) controlled, large sample, multi-center clinical trials can we get real results If the validation is effective, it can not only be widely used in China, but also be recognized all over the world Cheer for redceway! To Gilead, to researchers, to patients participating in clinical trials! 37 statement: This article only represents the author and does not represent the position of yaozhi.com You are welcome to communicate and supplement in the message area If you need to reprint, please be sure to indicate the author and source of the article.