1. Ethical Issues in Large Research and Medical Databases in Clinical and Research Multi-Centres Trials in China QIU Renzong Chinese Academy of Social Sciences/Peking Union Medical College

2. Large Research and Medical Databases Representatives of large research and medical databases in mainland China include: Genetic databases at National Human Genome Research Center (Beijing or North Center); Genetic databases at National Human Genome Research Center (Shanghai or South Center); Genetic databases of Chinese minorities (Kunming, CAMS); Databases of chronic diseases (CAMS): about half millions samples have been collected and stored in collaboration with UK; Plan to establish: Shanghai; Centre for Maternal and Child Health (Beijing, CDC).

3. Programme in Research and Medical Databases There is no special programme for setting up new large research or medical databases in the middle-long term programmes for the development of science and technology. However, with the progress of the achievement of these programmes (e.g. developing new drugs) which involve multi-centres clinical trials, a number of large databases of particular diseases will be set up.

4. Ethical issues in databases/biobanks Database, especially biobank is a new thing, new type of institution. What is the distinctive? We need to understand it properly and take action to it properly. One distinctive is so many stakeholders involved: donors, patients, research subjects, their family members, research institutes, institutions which collect, store and manage samples and data, users of these sample and data, sponsors, companies, regulators/administrators, foreign and international organizations etc. How to properly handle the relationship between them? In Taiwan regulations on biobank (definition, establishing, collection of samples and protection of donors, management, use of samples, and penalty) was promulgated recently. In mainland China only some institute wants to develop a code of conduct.

5. Database/Biobanks Social Value Database/biobank is an endeavor in which risks involved in is minimum, but the potential benefit is enormous. So the net utility of biobank is very high, the positive value of risks/benefits ratio is great. Biobank is of a great social value, a social good. The following is mainstream response to ethical issues

6. Ownership of Biological Materials Donor is the owner of her/his biological materials, but not in the way he/she own car or clothes. Biological materials cannot be treated as property or commodity. Biological materials are better taken as gift voluntarily given to unnamed strangers without compensation, like blood or organ donation. The administrator of database/biobank is not the owner of biological materials stored in it, rather he/she is their guardian or steward.

7. General/Broad Consent with Opt-out General/broad consent with opt-out approach is a form of informed consent. It will help to balance between achieving public good and respecting individual autonomy. Need to prescribe specific conditions under which this approach may become a disguised coercion, and to develop precautionary measures to prevent it. General/broad consent may avoid the following case.

8. Second Use of Samples In HapMap project 200 blood samples were taken from Chinese donors and same number of samples were stored in US and China. One day US side requested to use the samples for other purpose than HapMap, Chinese side did not agree because in consent form signed by donors there was no article on further use of the sample. General/broad consent may avoid this event. It is difficult to predict exactly what kinds of use scientists may have in the future,

9. Promotion of free Flow More effective and wider flow of information kept in one countrys biobanks not only in native country but also between countries will positively promote public good of native country and the humankind. In this regard nations interest and humankinds interest is mutual and interdependent. Any ideological and practical barriers hindering this free flow should be examined, reviewed and removed.

10. Building an Equitable Relationship in the International Research Collaboration Mutual respect Equality Reciprocal benefits Informed consent Interim Measures for the Administration of Human Genetic Resources (1998)

11. Avoid Exploitation One US institute and an institute of nutrition (without the experiences of conducting genetic study) in Beijing signed an agreement in which Chinese side collected half million blood samples for US side in exchange of a lot of money. The concern is: Will China be merely a sample provider?

12. Gene Drain and Gene Warfare Chinese scientists and regulators are very sensitive at gene drain. One of worries is about gene warfare. Some scientists/geneticists feared that US side use the samples taken from mainland and map/sequence Chinese genome in order to prepare gene warfare against China. The concern about gene warfare have had negative impact on international research collaboration, even many think it is just a speculation..

13. Reluctant to Give Out Each of the multi-centres is collecting and storing a number of biological materials and is reluctant to give them out to a central database/biobank. Because it is convenient to them to use these materials if kept in their own institute.

14. Inconsistency US pharmaceutical company L conducted RCT of a new drug to treat osteoporosis at multi-centers including about 10 hospitals. The trial group used new drug; the control group used placebo. Research participants would be middle aged or elderly patients with serious osteoporosis. The trial would last 1 year. IRB of PUMC Hospital rejected the protocol in view of high risk, but IRBs of other hospitals approved it.

15. SFDA Guiding Principles for Ethical Review in Drug Clinical Trials (2010) Article 31: The basic principles of ethical review of multi-centres clinical trials shall be consistency and timeliness. Multi-centres clinical trials may develop the procedures of collaborative review: 1. The ERC of institution in charge shall be responsible for the scientific validity and ethical legitimacy of the protocol; 2. The ERC of participating institutions shall be responsible for reviewing the feasibility of conducting the trials at its own institution and approve or disapprove whether the trails shall be conducted at its own institution. 3. The suggestions on the revision of the protocol the ERC of participating institutions considers the need to make shall be submitted to the sponsor or the institution in charge, and the unanimous opinion shall be reached.

16. Suggestions The government should be major sponsor, while welcome private foundations, companies to join. Large databases/biobanks should be non-profit organizations, like bio-libraries provided for use of researchers or any other legitimate use. Scientists and administrators of databases/biobanks should be trustworthy to the public. The public should be involved in consultation or engagement on databases/biobanks. National and international collaboration on access to data/samples and research should be promoted.

17. Thank you very much for your attention