This article is from WeChat public account: Nutshell (ID: Guokr42) , author: Zhang Di, editor: snow bamboo
The recent entry of Radixivir in clinical trials, known as a potent drug, has caused widespread discussion, and rumors related to it have also arrived. Rumors have even claimed that Redecive is effective in more than 90% of patients within 17-40 hours. There are those who deliberately spread rumors for their own benefit, those who cannot be discerned because of excessive bombardment of information, and more people wishfully think of Reddivevir as a “magic drug” because they hope this is true.
No matter what the rumors are, according to the New England Journal of Medicine (NEJM) , American doctors are the first case of a new type of coronavirus Patients with pneumonia were treated with Radixivir on the seventh day of admission, and their condition improved the next day. Many people have a simple question in mind: saving people is like fighting fires. Since drugs are effective in one patient, why can’t they be used directly in other patients?
Unable to do everything
To answer this question, we must first clarify the concept of clinical trials. Clinical trials are a form of medical research that involves testing new methods for preventing, diagnosing, or treating diseases in humans. Many of the current medical procedures and treatments are the result of past clinical trials, such as streptomycin for tuberculosis, anti-HIV drug Kelizhi, and HPV vaccine to prevent cervical cancer.
Clinical trials can be research: new drugs or new drug combinations, new surgical methods, new medical devices, or new uses of existing treatments (Such as the use of anti-HIV drugs to treat new coronary pneumonia) .
Two concepts are distinguished here, clinical medicine and clinical trials. The primary purpose of clinical medicine is to solve the health problems of individual patients. The treatment plan given by the doctor should be aimed at individual patients, in the best interests of patients. In contrast, the primary purpose of research is to obtain generalizable knowledge.
For clinical trials, the primary purpose is to obtain some kind of intervention that benefits the patient population. The former is to serve individual interests, and the latter is to improve the health of the entire group. The former looks at the symptoms at the moment, and the latter is planning for the future.
Clinical trials aim to improve the health of the entire population | Tuworm Creative
Specifically to this “specific medicine” Redecive. There is insufficient scientific evidence on whether the drug is effective in patients with neo-coronary pneumonia in the absence of clinical trials. Although a patient’s condition improved for a period of time after receiving Radixivir, first, First, for this patient, multiple drugs may be used in the course of treatment, and the patient’s recovery cannot be determined to be the effect of one of these drugs;
Second, for certain diseases, such as neo-coronary pneumonia, chickenpox, rotavirus enteritis, etc., they are self-limiting, that is, patients may heal themselves without antiviral treatment. This means that a certain patient has used an experimental drug from onset to recovery, but this does not prove that the drug is effective for the treatment of a certain disease. The patient’s recovery may be due to the effects of other drugs, or the combined effects of experimental drugs and other drugs, or due to the patient’s own immunity, which does not prove that the experimental drugs are effective.
In addition, even if there is some scientific evidence to support the positive effect of the experimental drug in curing a patient, it cannot be directly introduced to be effective in other patients. First, there are genetic differences between individuals, which is especially true in the treatment of tumors.Prominently, the same drug is effective for some patients and some patients are not effective;
Second, the drug may have serious side effects. Due to the differences between individuals, some patients may use the experimental drug to have serious side effects. Before being subjected to rigorous clinical trials, they are used in large areas in clinical medicine. Experimental drugs may cause more risk / harm than benefits in the community.
This is why many countries have established drug regulatory agencies, and passed legislation requiring that only those that have passed rigorous clinical trials and the test data proves that the drug is safe and effective. Used by a large number of patients.
There is insufficient scientific evidence on whether Radixvir is effective in patients with new coronary pneumonia | Tuworm Creative
For the clinical application of Radixivir, Academician Zhong Nanshan once said that clinical trials can speed up the green channel, but must follow the procedure. “Many laboratories find a sign and hope to enter the clinic completely immediately. Be careful, and ethical review must pass. Clinicians still have to do according to clinical rules.”
Ethical guidelines for clinical trials in the face of a major epidemic
In order to ensure the scientificity of the trial process and results, and to protect the interests of the subjects, clinical trials, whether conducted during an outbreak or not, should comply with scientific standards and ethical norms. The ethics guidelines of the WHO and the International Council for Medical Sciences point out that clinical trials at the outbreak of an epidemic should follow the following ethical principles, which are in line with China’s “Ethical Review Methods for Biomedical Research Involving Humans” and “Clinical Drug Trials” The Guidelines for Ethical Review Work are consistent.
1. Scientificity of research
Research design must be urgentIt is practicable under the circumstances, and its scientific validity must be ensured, otherwise its process and results are problematic and the research purpose cannot be achieved. If research is not scientifically effective, it should not be carried out, otherwise not only will it not be able to derive valuable scientific knowledge or create social value, it will also disperse effective medical resources, research resources and funds, etc., which may hinder the effectiveness of emergency situations. Handle / respond.
2. Assess potential benefits and risks to individual subjects
For all potential patients (potential subjects) that meet the inclusion criteria, the investigator should evaluate the drug for individual subjects Benefits and risks. Researchers should also evaluate whether patients have alternative treatment options in addition to participating in the study. For example, should mild patients be included in the trial? If there may be better treatment options for the patient outside the study, participation in the study may not be in the best interest of the patient, and the risk may be greater than the benefit for the individual patient.
According to the Xinhua News Agency, the traditional trial is divided into 1: 1 groups, while in the clinical trial of Radixivir for patients with severe new coronary pneumonia, the number of test and control groups is 2: 1. From an ethical perspective, such groupings can provide more critically ill patients with the opportunity to use experimental drugs, increasing the overall potential benefit of subjects in clinical trials. Of course, this refers to the potential benefit, that is, the benefit will only be realized if the experimental drug is really effective.
Criteria for the selection of severe patients in this Redecive clinical trial | ClinicalTrials.gov
3. Informed consent
In the context of the current epidemic, some patients with neo-coronary pneumonia may lose their ability to judge, and the judgment of a single subject is not limited.On their behalf, they do not have the ability to make decisions. Informed consent should be made in a way that is understandable to such subjects. When the subjects do not have the capacity to make judgments, the investigator should obtain the proxy consent of the subject’s guardian.
Medical staff need to give professional advice from the professional perspective in the best interests of patients, and respect the patient’s autonomous choice. When considering the inclusion of patients in research, the differences between clinical trials and treatment should be emphasized to patients. The primary purpose of trials is to obtain generalizable knowledge, not to address the health problems of individual patients.
In the informed consent process, the researcher should clearly inform the subjects that in addition to participating in clinical trials, they can also choose other treatment options, such as those currently mentioned in the updated guidelines for the treatment of new coronary pneumonia. In addition, inform the subjects of the risks and possible benefits of participating in the trial, as well as the benefits and risks of not participating in the trial and receiving other treatment options, so that patients can make informed choices.
When the treatment data for new coronary pneumonia continue to accumulate and it is found that a more effective treatment plan for these subjects, the subjects should be informed in time to let them determine whether to continue participating in the trial or to withdraw from acceptance. May be more effective treatment. In addition, the researcher should inform the subject that he or she has the right to withdraw from the research trial at any time during the trial without penalty.
4. Fair choice for participants
In emergency situations, experimental interventions are often scarce resources and often involve ethical issues in resource allocation. Especially in emergencies, wealthy and socially related patients should not be granted privileges to join the group. In addition, there must be valid reasons for excluding vulnerable groups, such as the elderly and minors. When recruiting, given specific reasons, certain specific groups of people can be given priority consideration, such as first-line medical institution staff, logistics and distribution staff: if the intervention proves effective, they can quickly return to work and put in emergency treatment.
5. Community participation
Disasters often lead to the vulnerability of groups and individuals and make the social environment fragile. Involving local communities in research as early as possible is critical to maintaining public trust and ensuring that research is culturally sensitive. Encouraging the community to take a leading role in research is important to help dispel mistrust and effectively promote communication so that research design can be supported.
6. Results return and data sharing
Whether the study yields negative or positive results, information should be made public in a timely manner to expedite the effective adjustment of interventions during the epidemic. If the research results in effective interventions, they should be shared as soon as possible, and the government and society should make the relevant interventions accessible to areas affected by the disease and avoid obstructing public interest protection due to patents.
7. Conflict of interest
Conflict of interest refers to a situation in which when there are multiple interests in an individual or organization, the realization of one interest may confront other interests. For example, in some studies, researchers maintain a rigorous and pragmatic attitude to conduct research in order to protect and promote the interests of the public. At the same time, the researcher may also hold the stock of the company behind the drug under study. May cause financial losses to their personal or funded research companies. Whether it is a domestic ethics review rule, an international ethics code, or an international journal publication rule, researchers are explicitly required to publish their conflicts of interest.
At present, in addition to the well-received redecvir, dozens of clinical trials related to new coronavirus pneumonia have been registered in the China Clinical Trial Registration Center, including both traditional Chinese medicine and western medicine. Shuanghuanglian oral solution. Research funding varies. The research on Shuanghuanglian Oral Liquid was funded by Harbin Pharmaceutical Group Sanjing Pharmaceutical Co., Ltd., which produces Shuanghuanglian.
It needs to be pointed out that the existence of conflicts of interest does not mean that researchers will necessarily reach results that are beneficial to themselves or their funders. By publishing conflicts of interest, researchers can increase the transparency of information, thereby increasing the public’s trust in researchers and institutions, and avoiding or reducing research that is not ethical due to conflicts of interest, and harm the interests of subjects and the public.
Screenshot of project information | China Clinical Trial Registry
We all hope to find effective drugs for new coronavirus pneumonia as soon as possible, but the effectiveness of the drugs needs to be verified through rigorous scientific tests. According to the registration information of two clinical trials of Radixivir for the treatment of new coronavirus pneumonia on the Clinical Trials.gov database in the United States, clinical trials for patients with moderate and mild symptoms will begin on February 5th, and the trial will be completed on April 27th. . Trials in the intensive group also began on February 5 and are expected to end on May 1. Until then, Fang was conclusive.
References:
[1] Holshue ML, DeBolt C, Lindquist S, et al. First Case of 2019 Novel Coronavirus in the United States. New England Journal of Medicine 2020 doi: 10.1056 / NEJMoa2001191
[2] 2016 International ethical guidelines for health-related research involving humans. Available at https://cioms.ch/shop/product/international-ethical-guidelines-for- health-related-research-involving-humans / [Access at Feb 8 2020]
[3] NIH Clinical Research Trials and You.
Available at https://www.nih.gov/health-information/nih-clinical-research-trials-you/basics [Access at Feb 8 2020]
[4] NIH Definition of a Clinical Trial. Available at https://grants.nih.gov/policy/clinical-trials/definition.htm [Access at Feb 8 2020 ]
[5] The Basics of Clinical Trials. Available at https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/what- you-need-to-know / clinical-trial-basics.html [Access at Feb 8 2020]
[6] Severe 2019-nCoV Remdesivir RCT. Available at https://clinicaltrials.gov/ct2/show/NCT04257656
[7] Mild / Moderate 2019-nCoV Remdesivir RCT. Available at
https://clinicaltrials.gov/ct2/show/NCT04252664
[8] National Health and Family Planning Commission. Measures for ethical review of biomedical research involving humans. 2016. Order of the National Health and Family Planning Commission of the People’s Republic of China11 #
[9] State Food and Drug Administration. Guiding Principles for Ethical Review of Drug Clinical Trials. 2010. Guo Food and Drug Administration Note [2010] 436 #
This article is from WeChat public account: Nutshell (ID: Guokr42) author: Zhang Di, editor: snow bamboo