Dear Director of the Ethics Committee, Members:
The following is a report on the ethical issues related to the Phase X clinical trial program of xxx drug, for review by the Ethics Committee. I. Qualifications and experience of investigators, conditions and equipment of the trial institutions
1. Curriculum vitae of the principal investigators of each center: specialty, education and degree, technical title, GCP training
2. Curriculum vitae of the principal investigators of the institution (including training in clinical pharmacology), published papers related to the trial specialty, other clinical trials of new drugs, scientific research projects, medical teaching work undertaken at the same time, Administration and management, etc., to show whether he/she has the professional experience related to this clinical trial, and whether he/she has sufficient time to undertake the task of this clinical trial.
3. A list of investigators, research assistants, and research nurses in the hospital, as well as their titles, specialties, and division of labor in the study
4. The conditions of instrumentation and equipment for the main indexes of the trial, as well as the qualifications and experience of the relevant testing personnel, and the equipment and conditions for rescuing the treatment of adverse events.
Two, the overall design of the study of ethical issues 1. The basis of the study
The results of the test drug efficacy, toxicology experiments, including the quantitative and toxicological relationship.
The composition of the prescription (drug, dosage, daily dose equivalent to the amount of raw drug), and the known adverse effects of the constituent drugs. Whether the purpose of the study is in accordance with recognized scientific principles and is well supported by relevant scientific literature. 2. Study population
Subject inclusion and exclusion criteria were consistent with the effect of the trial intervention. 3. sample size
Sample size calculations and the likelihood of obtaining reliable conclusions with a minimum number of subjects. 4. randomization
Random assignment may expose subjects to harm by depriving them of known effective therapies, especially in randomized controlled trials in which the trial intervention is designed to prevent or delay fatal or disabling outcomes. See Risk Minimization Designs for developing appropriate responses.
5. Choice of control
The best available treatment is usually chosen from among safe and effective treatments.
The placebo control is based on: (1) the lack of effective alternative treatments; (2) the fact that placebo treatment carries only a small risk and produces only a small difference in physiologic measurements, such as a mild increase in serum cholesterol; or (3) the fact that delaying treatment or not treating results in only temporary discomfort with no serious adverse effects. (iii) The use of placebo does not increase the risk of any serious, or irreversible, harm to the subject when a positive control fails to produce reliable results.
6. Discontinuation of the Trial
The trial should be discontinued if during the course of the trial it is found that the risks outweigh the potential benefits, or if conclusive evidence of a positive beneficial result is obtained.
III. Benefits and Risks
1. Anticipated Benefits
Subjects will receive special supervision by a physician and free medical care during the study.
There will be early access to new drug treatments with promising clinical applications that may be formally approved for marketing by the Drug Administration in the future, especially when the test drug has certain therapeutic characteristics not found in marketed drugs.
Phase I and II clinical trials, generally considered that the test drug is not certain to offer the prospect of direct benefit to the subjects. 2. possible risks
①Therapeutic risks versus trial risks.
② Known or unknown adverse effects of the test drug.
3) Placebo-controlled concomitant risks.
④Subjects in randomized controlled trials are assigned to receive a treatment that has been shown to be less effective. 3. Inconvenience
The time spent participating in the trial, transportation, dietary control and activity restrictions. 4. Risk-minimizing design
1) Establishment of a monitoring system for adverse events: Designate a person or set up an independent data and safety monitoring committee to monitor the study data and to protect subjects from previously unknown adverse effects and from unnecessarily prolonged exposure to less effective treatments.
②To develop medical countermeasures against possible risks, such as treatment plans and procedures for possible adverse reactions, allowing for switching to a positive treatment in the event of intolerable symptoms, and the right of the investigator to discontinue the clinical trial in that case based on his or her own judgment, and other measures.
3) When the mechanism of action of the investigational treatment is different from that of the standard treatment, the experimental treatment and placebo may be added to the standard treatment. Specific occasions for this type of study are when the standard treatment is known to reduce mortality or the incidence of irreversible damage, when discontinuation of a recognized effective treatment may result in progressive disability, intolerable discomfort, or both, but when the trial is difficult to implement or difficult to explain by using the standard treatment as a positive control.
IV. Recruitment of Subjects 1. Population Characterization of Subjects
The selection of the subject population should follow the guidelines of equitable distribution of burden and benefits.
Special reasons for inviting vulnerable individuals (the elderly, children, pregnant women, people with intellectual or behavioral disabilities, and members of hierarchical groups who are inferior or subordinate, etc.) as subjects, and measures to protect their power and health.
2. Recruitment of subjects
Recruitment of subjects can be carried out through advertisements, or announcements of relevant information → interested parties to apply → read the "Introduction to the study" → physical examination and screening of volunteers → signing of informed consent by those who are qualified → randomization of the selected subjects → clinical trials.
The "Announcement of Recruitment of Subjects" and the "Introduction to the Study" are attached and submitted to the Ethics Committee for review.
V. Medical care and protection of subjects
1. Description of medical care available to subjects
The investigator is responsible for the medical care of subjects, and measures to make medical decisions related to the clinical trial. Measures in place to ensure that the subject can reach the investigator at any time (the investigator will leave a cell phone with the subject to ensure that the subject can reach the investigator at any time when needed). Subjects must be housed in the Phase I ward during the Phase I clinical trial, with the Clinical Pharmacology Laboratory physician, the Phase I ward physician, and the nurses responsible for the subject's medical care.
Subjects participating in a clinical trial will be provided with arrangements for free medical care (e.g., trial medications, physical and chemical tests, outpatient registration, additional or extended hospitalization, medical treatment for adverse events, etc.). Phase I clinical trials will be provided free of charge for all inpatient medical care and a standard meal allowance of xxx dollars per day.
The manner and duration of the investigational treatment will be provided at no cost to the subject if it continues after the study is completed. If the experimental treatment is ineffective, the standard treatment that will be obtained free of charge. Treatment options available to the subject in the event of voluntary withdrawal.
Emergency response plan for serious adverse events.
2. Compensation
A description of any compensation provided to the subject for participation in the study, such as compensation for transportation, test nutrition, lost wages for participation in the clinical trial, as well as medical care, necessary science books or education. The honorarium fee that will be given to the subject for exploratory clinical trials such as Phase I and Phase IIa.
Subjects who withdraw from the study for reasons related to the study, such as unacceptable side effects of the investigational drug, or for health reasons, shall be paid or compensated as if they had completed the study in its entirety. Subjects who withdraw from the study for other reasons shall be paid in proportion to the amount of work they participated in. The investigator has the right to deduct some or all of the remuneration for subjects who must be eliminated from the study because of willful noncompliance.
3. Insurance and Compensation
Arrangements for compensation for research-related injury, disability, or death will be made by the Investigator and the Clinical Trial Organization, who will provide medical treatment, and by the Sponsor, who will be responsible for the cost of treatment and compensation.
The sponsor shall provide insurance coverage for subjects participating in the clinical trial, and shall provide arrangements for legal and financial guarantees to the investigator (except when caused by medical malpractice).
VI. Protection of Subjects' Privacy
1. Only the investigators and monitors involved in the clinical trial may have access to the subjects' personal medical records, and they will sign an investigator's statement or confidentiality pledge that includes confidentiality. Ethics committees and drug regulatory authorities have the right to inspect clinical trial records.
2. Data will be processed in a data-anonymized manner, omitting personally identifiable information. If participation in a clinical trial (e.g., AIDS, impotence, etc.) may expose a subject to social discrimination, the medical record should be securely coded to preserve patient-identifying information.
3. The clinical trial organization responsible for keeping the trial records of subjects and the sponsor's data archive should establish strict security and confidentiality measures.
VII. Informed consent
1. The process of informed consent
The researcher shall use language and text that the subject or his/her lawful representative can understand, explaining the details of the clinical trial, including the purpose of the trial, the trial procedures, the possible benefits and risks, and the subject's rights and obligations, etc., so that the subject fully understands and has sufficient time to consider, and the questions are raised. After receiving satisfactory answers to their questions, they agreed and signed the informed consent form. When signing the informed consent form for each patient, the doctor should leave his/her contact telephone number to the patient, so that the patient can find the doctor at any time when there is a change in his/her condition. The person responsible for signing the informed consent form was the investigator.
The "Informed Consent Form" is attached and submitted to the Ethics Committee for review. 2. Re-obtaining Informed Consent
Informed consent should be re-obtained when there is a significant change in the conditions or procedures of the study, or when new information is obtained that may affect the willingness of the subject to continue participation in the study.
Informed consent should be reacquired at pre-determined intervals for long-term research projects, even if there are no changes in the design or objectives of the study.
3. Avoiding coercion and undue influence
Patients are concerned that refusal to participate in a study may harm the doctor-patient relationship, and physicians/investigators must ensure that the doctor-patient relationship will not be compromised regardless of their decision to participate in the study, with a neutral third party obtaining informed consent if necessary.
4. Exceptions to informed consent
Informed consent cannot be obtained from the person and his/her legal representative due to an emergency situation, and in the absence of a proven effective treatment, where the trial intervention is expected to save lives, restore health, or alleviate suffering, the population of persons with disease eligible for the study should be identified in the trial protocol, and the method of acceptance of these subjects should be described and approved in advance by the ethics committee. Committee's approval in advance.
VIII. Ethical review
1. Multicenter research can be achieved through an agreement between the centers, each center accepts the conclusions of the ethics committee of the leader unit to start the trial.
2. Any modification to the study protocol or informed consent, which may affect the rights and interests of the subjects or the implementation of the study, needs to be reported again to the Ethics Committee for approval before implementation.
3. Any serious adverse events occurring in the clinical trial shall be promptly reviewed by the Ethics Committee of each center, and written modifications shall be proposed, including sufficient power to suspend the trial, and inform the group leader unit and the sponsor for their consideration and corresponding actions, so as to ensure that all other subjects are protected and the study will be effective in all centers. Reporting of Findings
1. The contract specifies who has the authority to publish the results of the study and makes it mandatory that the manuscript reporting the results of the study be prepared in conjunction with, and subject to the advice of, the Principal Investigator.
2. In the case of negative results, the availability of such results is assured through public publication or reporting to the drug registration authority.
3. circumstances that might be considered inappropriate for the publication of research findings, such as epidemiologic, sociologic, or genetic research findings that might pose a risk to society, or to the interests of populations, or groups defined by race or ethnicity.
4. Each subject will be informed of any findings related to their own health status. Upon completion of the study, subjects will be informed of the manner in which the study findings were made.