Team:SYSU-MEDICINE/Ethics

Ethics

Ethics on clinical trial of MSCs therapy

After we carried out an interview with doctors and patients, we found out there were some ethic issues between researchers and patients.

To our surprise, we found that some doctors were worried that on hearing the very term ‘Experiment’, patients might choose to get treated elsewhere, and some thought that there was not enough time to explain details to patients. So, some investigators may shorten the consent form or deliberately omit some ‘offensive’ parts that might deter patients from agreeing to participate.

However, though written consent forms are used to document the consent, the process of informed consent is more important than a subject’s signature on the form.

Therefore, we hold the view that investigators must take particular care to be sure that anyone they ask to consider taking part in research is given the fullest possible information, presented in terms and a form that they can understand. This must include any information about possible benefits and risks; evidence that a research ethics committee has given approval; and advice that they can withdraw at any time. They should also ensure that participants have the opportunity to read and consider the research information leaflet and allow them sufficient time to reflect on the implications of participating in the study. Moreover, researchers cannot put pressure on anyone to take part in research.

For clearer understanding, we then turned to Professor Zhang , the head of Biological Treatment Center of The Third Affiliated Hospital, Sun Yat-sen University, for more information.

Specifically, when it turns to the clinical trail of MSCs therapy, according to professor Zhang, researchers must concern three essential principles. First of all, the whole cell therapy industry must be self-discipline. Secondary, we researchers are obliged to offer as much as information about clinical trial to patients and let them choose their preferred treatment by themselves. Last but not least, the whole treatment should be well regulated by related government department, such as CFDA.

In conclusion, no matter what clinical trial we are carrying out, three principles should be received great concern: autonomy, beneficence and justice , not only for the research result, but also for patients’ heath as well as sustainable development.

Reference:
http://medind.nic.in/iad/t03/i1/iadt03i1p30.pdf
http://aaalac.org/



Consideration of Animal Ethics and Welfare



1 & 2 Search information and interview

At the very beginning, we searched information of animal welfare and learnt how to construct animal models.
• Rationale and purpose of the proposed use of animals
• A clear and concise sequential description of the procedures involving the use of animals and timely intervention, removal of animals from a study, or euthanasia if painful or stressful outcomes are anticipated
• Availability or appropriateness of the use of less invasive procedures, other species, isolated organ preparation, cell or tissue culture, or computer simulation
• Justification of the species and number of animals proposed; whenever possible, the number of animals and experimental group sizes should be statistically justified (e.g., provision of a power analysis; see Appendix A, Experimental Design and Statistics)
• Duplication of experiments
• Housing and husbandry requirements
• Impact of the proposed procedures on the animals’ well-being
• Description and rationale for anticipated or selected endpoints
• Method of euthanasia or disposition of animals, including planning for care of long-lived species after study completion
• Adequacy of training and experience of personnel in the procedures used, and roles and responsibilities of the personnel involved
• Use of hazardous materials and provision of a safe working environment.


3 Improve our project and arrange materials

Our Project: To testify and verify the elevated homing ability of mesenchymal stem cells (MSCs) with over expressed chemokine receptors (CXCR1, CXCR4, CXCR5, CCR2, CCR5 and CCR7) and to research their distribution with assistance of marking proteins in inflammatory bowel diseases IBD and DTH (delayed type hypersensitivity) animal models.

According to principles of AAALAC International (Association for Assessment and Accreditation of Laboratory Animal Care), we standardized experimental conditions and designed our animal experiments.
• Firstly, we would strictly follow the protocols of animal model construction and scientifically group for them according to statistical analysis.
• Secondly, all experimental conditions would be supervised in order to ensure welfare and ethics of experimental animals. For example, all the mice in our experiments would be housed in laboratory animal house where temperature is set at around 24℃ and humidity was stabilized at around 70°F which are suitable for mice. Mice would share a standard Individually ventilated cage (IVC) laid one by one in racks which minimized the spread of airborne particles between cages or groups of cages with proper arrangement. The house was lightened by incandescent lamp and natural light.
• Thirdly, during the surgery, mice undergone insertion to colon may not suffer severe pain with appropriately anesthetization. Concentration and dosage of the solution had been stated ibid and decided with reference of articles and previous successful studies. If mice reached a stage where met the rationale for anticipated endpoint, we would carry out euthanasia for mice. For example, all the mice would be sacrificed by cervical dislocation.

4 Pass application forms of experimental animals

Finally, we were permitted for animal experiments. The approvals are showed below.

DTH
• SUN YAT-SEN UNIVERSITY, ZHONGSHAN SCHOOL OF MEDICINE APPROVAL DOCUMENT IN ETHICS COMMITTEE OF ZSSOM LABORATORY ANIMAL CARE
• SUN YAT-SEN UNIVERSITY, ZHONGSHAN SCHOOL OF MEDICINES APPLICATION FORM FOR ETHICAL REVIEW OF WELFARE AND ETHICS OF EXPERIMENTAL ANIMALS

IBD for Confirmation
• SUN YAT-SEN UNIVERSITY, ZHONGSHAN SCHOOL OF MEDICINE APPROVAL DOCUMENT IN ETHICS COMMITTEE OF ZSSOM LABORATORY ANIMAL CARE
• SUN YAT-SEN UNIVERSITY, ZHONGSHAN SCHOOL OF MEDICINES APPLICATION FORM FOR ETHICAL REVIEW OF WELFARE AND ETHICS OF EXPERIMENTAL ANIMALS

IBD for Mathematics
• SUN YAT-SEN UNIVERSITY, ZHONGSHAN SCHOOL OF MEDICINE APPROVAL DOCUMENT IN ETHICS COMMITTEE OF ZSSOM LABORATORY ANIMAL CARE
• SUN YAT-SEN UNIVERSITY, ZHONGSHAN SCHOOL OF MEDICINES APPLICATION FORM FOR ETHICAL REVIEW OF WELFARE AND ETHICS OF EXPERIMENTAL ANIMALS

IBD for ShanghaiTechChina_B
• SUN YAT-SEN UNIVERSITY, ZHONGSHAN SCHOOL OF MEDICINE APPROVAL DOCUMENT IN ETHICS COMMITTEE OF ZSSOM LABORATORY ANIMAL CARE
• SUN YAT-SEN UNIVERSITY, ZHONGSHAN SCHOOL OF MEDICINES APPLICATION FORM FOR ETHICAL REVIEW OF WELFARE AND ETHICS OF EXPERIMENTAL ANIMALS

Discussion —— Primates experiments

During the experiments, we once noticed that primates are used in other research team in the lab. Then we found that Professor Xiang has project about primates, which are bought from Guangdong Blooming-Spring Biological Technology Development Company.


Then how about our project in the future? Will we use primates to do experiments before clinical trials? Is it necessary? Is there any other animals can replace primates? We discussed these questions with Xiang. For safety concern, the reaction of primates is the most similar to human, which is the reason why we use primates to do some experiments. However, animal experiments must follow ‘Three R’ principles, reduction, replacement and refinement. So, it is not sure whether our project is going to do primates experiments, which need to do further assessment in the future.

When you see the eyes of the monkeys on the photos above, how do you feel? Lovely? Cute? It seems really difficult to treat primates as experimental animals.
It has been a contradiction between medical development and animal protection. New drugs are always built on a grate amount of death animals, which sounds crucial but we cannot test new drugs on human first. Most scientists have to do animal experiment for human health. Primate experiments do make a great improvement in medical such as in AIDS and some emerging infectious diseases.
Sacrifice of some animals can save more human, but what about the equality of life?

Is it correct or not to use primates for medical development? What is your opinion?



Reference：
http://www.nsfc.gov.cn/nsfc/cen/pfzl/pufanew/20110801_02.pdf

http://www.lascn.com/SupplyDemand/Site/Index.aspx?id=121