Role of EC

2. Role of EC/IRB

3. Research process

4. Research process

5. History of Ethical Problems in Biomedical Research

6. History of informed consent In 1900, Dr. Albert Neisser, German physician, studied infected patients (mainly prostitutes) with syphilis without their consent. Against by the academic community and public opinion �A legally based, positivistic contract theory of the patient-doctor relationship" that was not adopted into German law

7. Nazism Nazi Party (1920-1945) World War II

8. Nazi human experimentation A series of controversial medical experiments on large numbers of prisoners during World War II. Prisoners were coerced into participating: They did not willingly volunteer and there was never informed consent. Typically, the experiments resulted in death, disfigurement or permanent disability.

9. Examples of Nazi Experiments Freezing Malaria Mustard Sulfonamide Sterilization Poison

11. Experiments with Poisons The poisons were secretly administered to experimental subjects in their food. The victims died as a result of the poison or were killed immediately in order to permit autopsies.

12. Sterilization experiments To develop a method of sterilization which would be suitable for sterilizing millions of people with a minimum of time and effort. These experiments were conducted by means of X-ray, surgery and various drugs. Thousands of victims were sterilized compulsory.

13. Aftermath Many of the subjects died or were murdered after the tests to study the effect post mortem The German doctors captured by Allied forces were put on trial which is commonly known as the Doctors' Trial.

14. Japanese Experiments during WWII The results from Unit 731 were kept classified by the USA The majority of doctors involved were given pardons

15. The Nuremberg Doctors Trial of 1946

16. Nuremberg Code At the trial, several of the doctors argued in their defense that there was no international law regarding medical experimentation. The development of the Nuremberg Code of medical ethics. 1947

17. Nuremberg Code The Nuremberg code includes such principles as informed consent and absence of coercion; properly formulated scientific experimentation; and beneficence towards experiment participants.

19. Thalidomide Thalidomide was approved as a sedative in Europe in the late 1950�s. The FDA never approved the drug, but samples were sent to US doctors. By 1961 thalidomide was shown to be very harmful to the fetus, interfering with the normal development of arms and legs.

20. Thalidomide These events lead to the passage of the Drug Amendments of 1962 to the Food, Drug and Cosmetic Act. This was the first US statues that required subjects be informed of a drugs experimental nature and to consent before starting the research study.

22. �Syphilis Victims in US Study Went Untreated for 40 Years� US Public Health Service studies syphilis in Black men

23. Tuskegee Syphilis Study: 1932-1972 When the study began in 1932, standard medical treatments for syphilis were toxic, dangerous, and of questionable effectiveness By 1947 penicillin had become the standard treatment for syphilis. Prior to this discovery, syphilis frequently led to a chronic, painful, and fatal multisystem disease

24. The Belmont Report is an important historical document in the field of medical ethics The report was created on 1979 Prompted in part by problems arising from the Tuskegee Syphilis Study (1932-1979) Department of Health, Education and Welfare (HEW) revised and expanded its regulations for the protection of human subjects

25. The Three Fundamental Ethical Principles respect for persons: protecting the autonomy of all people and treating them with courtesy and respect and allowing for informed consent; beneficence: maximizing benefits for the research project while minimizing risks to the research subjects justice: ensuring reasonable, and well-considered procedures are administered fairly (the fair distribution of costs and benefits.)

26. International Guidelines Nuremberg Code Declaration of Helsinki Council for International Organizations of Medical Sciences (CIOMS) International Conference on Harmonization �Guideline for Good Clinical Practice�(ICH/GCP) WHO guidelines

27. The Declaration of Helsinki The Declaration of Helsinki was developed by the World Medical Association (WMA), as a set of ethical principles for the medical in 1964 community regarding human experimentation. It is widely regarded as the cornerstone document of human research ethics Although it is not a legally binding instrument in international law

28. The Declaration of Helsinki The Declaration developed the ten principles first stated in the Nuremberg Code. The Declaration more specifically addressed clinical research. A notable change from the Nuremberg Code was a relaxation of the conditions of consent, which was 'absolutely essential'

29. First revision (1975) Introduction the concept of oversight by an 'independent committee� which became a system of Institutional Review Boards (IRB) in the US, and research ethics committees or ethical review boards in other countries. In the United States regulations governing IRBs came into effect in 1981

30. Second to Sixth Revisions (1975-2008) In1994, WHO group concluded "Placebo-controlled trials offer the best option for a rapid and scientifically valid assessment of alternative antiretroviral drug regimens to prevent transmission of HIV". Direct conflict with CIOMS, which stated "The ethical standards applied should be no less exacting than they would be in the case of research carried out in country�

31. The Declaration of Helsinki From 1982, the Declaration was not alone as a universal guide CIOMS and the World Health Organization (WHO) had also developed their International Ethical Guidelines for Biomedical Research Involving Human Subjects.

32. Principles of the Declaration The Declaration is morally binding on physicians The obligation overrides any national or local laws or regulations, if the Declaration provides for a higher standard of protection of humans than the latter. Investigators still have to abide by local legislation but will be held to the higher standard.

33. The CIOMS Guidelines Created in 1993 by the Council for International Organizations of Medical Sciences (CIOMS) and updated in 2002 these 21 guidelines (15 in the original report) address issues including informed consent, standards for external review, recruitment of participants, and more. The Guidelines are general instructions and principles of ethical biomedical research

34. Good Clinical Practice (GCP) is an international quality standard It also provides assurance of the safety and efficacy of the newly developed compounds. GCP Guidelines include standards on how clinical trials should be conducted, define the roles and responsibilities of clinical trial sponsors, clinical research investigators, and monitors.

35. ICH-GCP The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a project that brings together the regulatory authorities of Europe, Japan and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of pharmaceutical product registration.

36. ICH GCP overview Guidelines for the investigator Guidelines for the trial sponsor (industrial, academic) Guidelines for the clinical trial protocol and protocol amendments Guidelines for the Investigator's brochure

37. IRB and EC

38. Institutional Review Board (IRB) also known as an independent ethics committee (IEC) or ethical review board (ERB) to approve, monitor, and review biomedical and behavioral research involving humans to protect the rights and welfare of the research subjects. USA regulations, (FDA and Office for Human Research Protections, OHRP) have empowered IRBs to approve, modifications or disapprove research.

39. Ethics Committee (European Union) The Ethics Committee, according to Directive 2001/20/EC, is an independent body With the Clinical Trials Directive, the European Union (EU) envisioned a harmonisation of research ethics committees (RECs) across Europe,.

40. IRB or EC Approval Criteria Risks to subjects minimized Risks to subjects reasonable in relation to anticipated direct benefit knowledge to be gained Selection of subjects equitable Informed consent sought and documented Appropriate provisions for monitoring safety Provisions for confidentiality Additional safeguards for vulnerable populations

41. WHO guidelines Operation guidelines for Ethical Committees that review biomedical research, WHO 2000

42. The basic principles of the ethical issues Respect for persons Beneficence (beneficent) Justice (fairness)

43. Vulnerable population include some individuals who have limited autonomy such that they cannot fully participate in the consent process. Prisoners Children Subordinate Individuals Decisionally Impaired.

44. Informed Consent Informed consent: right to know, right to self determination The hallmark of consent are informed understood Voluntary - Oral, implied: to communicate and idea without saying it directly , written consent

45. Research Ethics in Thailand

46. ????????????????????????????????????????????????????????? (???????5) ?.?. 2544 ??????? 6 ????????????????????????????? ??????5 ?????????????????????????????????????????????????????????????????????????? ?????????????????????????????????????????????????????????????????? ????????????????????????????????????????????????????????????????????????? ????????????????????????? ?????? 8 ?????????? 2544 ??????????????????????180??????????????????????????? (1 ??????? 2544)

47. �??????????????????????� ??????????? ??????????????????? ?????? ??????????????????????????????????????????????????????????????????????????????????????????????????????????????????? ????????????????????????????????????????????????????????????????????????????? ???????

48. ?????????????? ????????????????????????????? ??????????????????????????????????????????????????????Ethical Committee of the Bangkok Metropolitan Administration ??????????? 2541 ?????????????????????? 2634/2544 ???????????????????????????????????????????????????????? ?????????????????????????????????????????? ???? ? ?????? 27 ??????? 2544

49. ??????????????????????????????????????? ????????????????????????????????????? ?? ????? ???????????? ?????????????????????????????????????????? ???????????? ?????????????????????????????????? ?????????????????????????? ????????????????????????????????????

50. ??????????????????????????????

51. ??????????????????????? ???????????????????????????????????????????????????? ????????????? ????????????????? 2 - 3 ?????

52. Funding

53. Funding in BMA Medical College and Vajira Hospital ?????????????????????? ????????????????? ???????????? 40,000 ??? ??????????????????????????? ???. ???????????? 100,000 ???

54. Communicate The Results

55. Knowledge Index Medicus Pubmed Impact factor Citation International journal National journal

56. Index Medicus is a bibliographic listing of references from biomedical journals worldwide National Library of Medicine, National Institute of Health Pubmed (www.nlm.nih.gov) included 4,844 journals till January 2005 N Eng J Med, JAMA, Lancet, Ann Intern Med, Annu Rev Med, Arch Intern Med, BMJ, Am J Med,

57. ICMJE: International Committee of Medical Journal Editors Informal meeting of medical journal editors in 1978: Vancouver group Expanded and evolved to ICMJE Multiple editions of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals. (last revision 2001) Clinical trial registration www.icmje.org

58. Journal impact factor (JIF) Institute for Scientific Information (ISI) in USA Journal citation report

59. Journal impact factor (JIF) ISI was founded in 1961 AD. Tool for selecting the journal into the database 3 databases

60. Databases of ISI Science citation index 5,876 journals High JIF: N Eng J Med, JAMA, Lancet, Ann Intern Med, Annu Rev Med, Arch Intern Med, BMJ, Am J Med, Medicine, Social science citation index 1,700 journals Arts and humanities citation index 1,130 journals

61. 3 indexes of Journal impact factor (JIF) journal impact factor immediacy index cited half-life ????????????????????????????? ????????????????????????????? ??????????????????????????????????????????????????? ?????????????? ?????????? ???????????????????????????????????? ?????????? ? ????????????????????????????????????????????????????????????????????

62. JIF = number of citation in year (x) from articles in year (x-1) and (x-2) of that journal / sum of articles published in year (x-1) and (x-2) of that journal Technique of calculation

63. Thailand Citation Index (TCI) Citation information of local journals Report Thai Journal Impact Factor

64. List of approved local journals ?????????????????????????????? (???.) ?????????????????????????????????????? ????????????????????????????????????????????????????????????? ???????????????????????????????????????? ???????????? ?????? ???????? 2550

65. List of approved international journals Asian Pacific Journal of Allergy and Immunology The Southeast Asian Journal of Tropical Medicine and Public Health Journal of the Medical Association of Thailand Siriraj Hospital Gazette (??????????) Chulalongkorn Medical Journal (????????????????)

66. List of approved international journals ScienceAsia: Journal of the Science Society of Thailand Songklanakarin Journal of Science and Technology ECTI Transactions on Electrical Eng., Electronics, and Communication Thai Journal of Agricultural Science Asian Journal of Energy and Environment Journal of Environmental Research Thai Forest Bulletin

67. List of approved national journals ??????????????????????????????????????????????????????????????????? ??????????????????????????????????????????????????????????????????????? ??????????????????????????? ??????????????????????????? ???????????????????????? ????????????????????? 39 ????

68. List of approved national journals Thai Journal of Hematology and Transfusion Medicine Vajira Medical Journal (??????????) Journal of the Nephrology Society of Thailand Internal Medicine Journal of Thailand ???????????????????????????? ?????????????????