1. © 2004 Aeras Global TB Vaccine Foundation Intermediate Clinical Research Clinical Research Practice 2

2. © 2005 Aeras Global TB Vaccine Foundation 2 2 Purpose: To provide an in depth understanding of Good Clinical Practice and ethical guidelines for clinical research and the protection of research participants.

3. © 2005 Aeras Global TB Vaccine Foundation 3 3 In This Course You Will Learn To:  Identify the key events and documents that led to the standards and ethical principles that guides the conduct of clinical research today.  Recognise the key factors or guidelines for clinical research that emerged from the primary events or documents that guides current clinical research ethics.  Name the key international guidelines that were adopted and followed as part of the South African guidelines for the conduct of clinical research.  Identify special populations that have additional guidelines for their protection during clinical research under SA GCP guidelines.

4. © 2005 Aeras Global TB Vaccine Foundation 4 4 In This Course You Will Learn To:  Describe the guidelines for the inclusion of children and adolescents and vulnerable communities in clinical research.  List the 4 primary means of protection offered to study participants under GCP guidelines throughout the conduct of a study.  Identify the 4 phases of clinical trials.  Identify who is responsible for ensuring that research is performed and data generated in compliance with GCP guidelines and other applicable regulations.

5. © 2005 Aeras Global TB Vaccine Foundation 5 5 Do You Remember? What is clinical research? Why do we perform it? What happens in clinical research?

6. © 2005 Aeras Global TB Vaccine Foundation 6 6 What Is Clinical Research? A scientific study looking for answers to specific questions. A scientific study looking for answers to specific questions. Method for finding safe, new and improved vaccines, drugs, and other treatments to improve health. Method for finding safe, new and improved vaccines, drugs, and other treatments to improve health. Research that relies on human volunteers. Research that relies on human volunteers.

7. © 2005 Aeras Global TB Vaccine Foundation 7 7 Why Do We Perform Clinical Research? Test new therapies and drugs. Test new therapies and drugs. Gather data from participants who have had a known intervention and monitor results. Gather data from participants who have had a known intervention and monitor results. Determine the safety and effectiveness of drugs, therapies, and other treatments. Determine the safety and effectiveness of drugs, therapies, and other treatments. Develop new drugs and treatments that are safer, more effective and faster working than any before. Develop new drugs and treatments that are safer, more effective and faster working than any before. Ultimately – to improve health status. Ultimately – to improve health status.

8. © 2005 Aeras Global TB Vaccine Foundation 8 8 Define Research Question (What do you want to know?) The Life Cycle Of A Clinical Research Project Write a Research Proposal Find Funding & Select Research Team Write Protocol Conduct Research Analyse Results Report Results Get Regulatory Approval

9. © 2005 Aeras Global TB Vaccine Foundation 9 9 Study or Trial? All trials are studies but not all studies are trials. Do you know what the difference is? During a clinical trial a specific intervention needs to be tested on humans. Which of the studies at our site can be classified as trials?

10. © 2005 Aeras Global TB Vaccine Foundation 10 Four Phases of Clinical Trials Trials with a drug safety aspect has to go through the following phases, before making the drug or vaccine widely available to the public. Phase I Phase II Phase III Phase IV

11. © 2005 Aeras Global TB Vaccine Foundation 11 Phase I New drugs/treatment are tested on humans for the first time. New drugs/treatment are tested on humans for the first time. Small group of volunteers (30-50) Small group of volunteers (30-50) Healthy : 21+ years of age Healthy : 21+ years of age Goal: Determine the effect of the drug on a person’s body at a physical/physiological level. Goal: Determine the effect of the drug on a person’s body at a physical/physiological level. “Is the treatment safe ?” “Is the treatment safe ?”

12. © 2005 Aeras Global TB Vaccine Foundation 12 Phase II Phase I completed = treatment safe thus far Phase I completed = treatment safe thus far Less than 100 Volunteers Less than 100 Volunteers Disease specific volunteers Disease specific volunteers Conduct Randomised trials in order to compare the Experimental drug with a Placebo or the standard treatment. Conduct Randomised trials in order to compare the Experimental drug with a Placebo or the standard treatment. Goal: Determine safety and efficacy. How it should be given, how often and how much is safe? Goal: Determine safety and efficacy. How it should be given, how often and how much is safe? “Can the treatment work ?” “Can the treatment work ?”

13. © 2005 Aeras Global TB Vaccine Foundation 13 Phase III Phase II completed Phase II completed Hundreds - thousands of volunteers Hundreds - thousands of volunteers Conduct Randomised and Blinded studies. Conduct Randomised and Blinded studies. Goal: Determine safety, efficacy, benefits and the range of possible adverse reactions in the broader community. Goal: Determine safety, efficacy, benefits and the range of possible adverse reactions in the broader community. Approval for the market. Approval for the market. “Is the new treatment better than existing treatment or placebo?” “Is the new treatment better than existing treatment or placebo?”

14. © 2005 Aeras Global TB Vaccine Foundation 14 Phase IV Post market Post market Hundreds - thousands of volunteers Hundreds - thousands of volunteers Goal: Determine additional information including the drug’s risks, benefits, and optimal use. Goal: Determine additional information including the drug’s risks, benefits, and optimal use. “Is there a better way to use this treatment ?” “Is there a better way to use this treatment ?”

15. © 2005 Aeras Global TB Vaccine Foundation 15 It does not matter what type or kind of clinical research we conduct. If there are humans involved in the research there is one condition that absolutely has to be met. Do you know what it is?

16. © 2005 Aeras Global TB Vaccine Foundation 16 Protection of Human Participants Good Clinical PracticeGood Laboratory Practice

17. © 2005 Aeras Global TB Vaccine Foundation 17 Good Clinical Practice Good Clinical Practice An international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human volunteers. An international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human volunteers. Simply put …. GCP is the set of rules by which we conduct our research. Simply put …. GCP is the set of rules by which we conduct our research.

18. © 2005 Aeras Global TB Vaccine Foundation 18 Good Laboratory Practice Good Laboratory Practice Represents a set of principles that provides a framework within which laboratory studies are planned, performed, monitored, recorded, reported and archived. Represents a set of principles that provides a framework within which laboratory studies are planned, performed, monitored, recorded, reported and archived. Simply put …. Simply put …. GLP is the set of rules of research in the lab. GLP is the set of rules of research in the lab.

19. © 2005 Aeras Global TB Vaccine Foundation 19 Why Is Following GCP and GLP Important ? Compliance with these standards assures: participant rights are protected. participant rights are protected. the safety of human volunteers. the safety of human volunteers. participant well-being is a priority. participant well-being is a priority. results are used for improvement of health and well-being of all. results are used for improvement of health and well-being of all.

20. © 2005 Aeras Global TB Vaccine Foundation 20 The Protection of Human Participants An introduction to GCP and GLP is not enough to understand the complexities of the ways in which the Human Research Participant must be protected. We need to look at the codes, declarations, reports and guidelines that provides the: Ethical rules and principals and Ethical rules and principals and Foundational elements……. Foundational elements……. ……….for the conduct of clinical research. ……….for the conduct of clinical research.

21. © 2005 Aeras Global TB Vaccine Foundation 21 So, …….. In the past there were abuses and unethical behavior. Science was put ahead of human rights, In the past there were abuses and unethical behavior. Science was put ahead of human rights, and the.. and the.. International community responded – new standards emerged. International community responded – new standards emerged.

22. © 2005 Aeras Global TB Vaccine Foundation 22 In the CRP 1 Module We looked at the Nuremberg Code Nuremberg Code Declaration of Helsinki Declaration of Helsinki Belmont Report Belmont Report ICH GCP……….. ICH GCP……….. Let’s dig a bit deeper into a bit more detail..

23. © 2005 Aeras Global TB Vaccine Foundation 23 History of the Nuremberg Code: Nazi Medical War Crimes: 1939 – 1945 Nazi Medical War Crimes: 1939 – 1945 Photos courtesy of US Holocaust Museum

24. © 2005 Aeras Global TB Vaccine Foundation 24 Nazi Experiments Using Children:  1939 - 1945 Photos courtesy of US Holocaust Museum

25. © 2005 Aeras Global TB Vaccine Foundation 25 The Nuremberg Trial 1946: 23 Nazi physicians on trial. 1946: 23 Nazi physicians on trial. “Permissible Medical Experiments” “Permissible Medical Experiments” The Nuremberg Code The Nuremberg Code Photo courtesy of USHMM.

26. © 2005 Aeras Global TB Vaccine Foundation 26 Nuremberg Code Published in 1947 Published in 1947 The first internationally recognized standard for human participant research. The first internationally recognized standard for human participant research. Consisted of 10 conditions and included: Consisted of 10 conditions and included: Voluntary consent Voluntary consent Risk/benefit ratio Risk/benefit ratio Right to withdraw from experiments. These conditions had to be met before research was ethically permissible. Right to withdraw from experiments. These conditions had to be met before research was ethically permissible.

27. © 2005 Aeras Global TB Vaccine Foundation 27 History of the Declaration of Helsinki Thalidomide disaster – late 1950’s Thalidomide disaster – late 1950’s Results of this tragedy: Results of this tragedy: FDA requiring pre-clinical safety reports FDA requiring pre-clinical safety reports Europe and UK developed reporting systems Europe and UK developed reporting systems Led to the Declaration of Helsinki Led to the Declaration of Helsinki in 1964 in 1964 Photo courtesy of The Teratology Society

28. © 2005 Aeras Global TB Vaccine Foundation 28 World Medical Association Declaration of Helsinki Developed by the World Medical Association in 1964. Developed by the World Medical Association in 1964. First significant effort of the medical community to regulate itself. First significant effort of the medical community to regulate itself. Legally binding. Legally binding. Latest version: October 2000 with notes of clarification in 2002 & 2004. Latest version: October 2000 with notes of clarification in 2002 & 2004.

29. © 2005 Aeras Global TB Vaccine Foundation 29 Declaration of Helsinki (DOH) Consists of 32 ethical principles and includes: Voluntary consent, Risk/benefit ratio and the Right to withdraw from experiments…… Voluntary consent, Risk/benefit ratio and the Right to withdraw from experiments……and Additional principles for medical research combined with medical care. Additional principles for medical research combined with medical care. Use of placebo. Use of placebo. Access of participants to the best proven methods identified by the study. Access of participants to the best proven methods identified by the study.

30. © 2005 Aeras Global TB Vaccine Foundation 30 History of the Belmont Report: Tuskegee Syphilis Study: 1932-1972 Tuskegee Syphilis Study: 1932-1972

31. © 2005 Aeras Global TB Vaccine Foundation 31 “This examination is a very special one and after it is finished you will be given a special treatment if it is believed you are in a condition to stand it.” “This is your last chance for special free treatment.”

32. © 2005 Aeras Global TB Vaccine Foundation 32 This was one of the strategies used to keep the participants happy.

33. © 2005 Aeras Global TB Vaccine Foundation 33 Then the Tuskegee Study Became Public and …… National commission – 1974 National commission – 1974 Published the “Ethical Principles and guidelines for the Protection of Human Subjects.” -1979 Published the “Ethical Principles and guidelines for the Protection of Human Subjects.” -1979 Belmont Report Belmont Report Identified three basic principles. Identified three basic principles.

34. © 2005 Aeras Global TB Vaccine Foundation 34 Respect for Persons  Individuals should be treated as autonomous agents  Persons with diminished autonomy are entitled to protection. Informed Consent  Participants, to the degree that they are capable, must be given the opportunity to choose what shall or shall not happen to them. Key required elements:  Information  Comprehension  Voluntary participation Principle Application

35. © 2005 Aeras Global TB Vaccine Foundation 35 Beneficence  Human participants should be treated in an ethical manner and protected from harm.  Research should maximize possible benefits and minimize possible harm. Assessment of Risk and Benefit  The nature and scope of risks and benefits must be assessed and balanced in a systematic manner. Principle Application

36. © 2005 Aeras Global TB Vaccine Foundation 36 Justice  The benefits and risks of research must be distributed fairly and without bias. Selection of Participants  There must be fair procedures and outcomes in the selection of research participants. Principle Application Last 3 slides : Courtesy of the Claremont Graduate University: History of Ethics

37. © 2005 Aeras Global TB Vaccine Foundation 37 Did the Nuremberg Code & the Declaration of Helsinki Change the Conduct of Clinical Research? NO ! The Research Community needed something to: Ensure that the rights, safety and well-being of trial participants are protected Ensure that the rights, safety and well-being of trial participants are protected Ensure the credibility of clinical trial data Ensure the credibility of clinical trial data

38. © 2005 Aeras Global TB Vaccine Foundation 38 So, What Happened ? Belmont Report - 1979 ICH GCP - 1990 CIOMS - 1993

39. © 2005 Aeras Global TB Vaccine Foundation 39 International Conference on Harmonization 1990 World Health Organisation (WHO) – planned to standardise requirements for registration of new drugs: World Health Organisation (WHO) – planned to standardise requirements for registration of new drugs: Many sets of guidelines all over the world. Many sets of guidelines all over the world. High cost of clinical trials and ethical considerations of repeating trials when drug efficacy was already demonstrated. High cost of clinical trials and ethical considerations of repeating trials when drug efficacy was already demonstrated. International Conference on Harmonization in 1990 – Brussels International Conference on Harmonization in 1990 – Brussels Published the ICH GCP Guidelines Published the ICH GCP Guidelines

40. © 2005 Aeras Global TB Vaccine Foundation 40 What Does ICH GCP Cover? Consists of 13 Principles Consists of 13 Principles Covers guidelines for the conduct of research: Covers guidelines for the conduct of research: Ethics Ethics Essential documents Essential documents Investigator Investigator Protocol Protocol Investigator’s Brochure Investigator’s Brochure Sponsor Sponsor

41. © 2005 Aeras Global TB Vaccine Foundation 41 The Establishment of CIOMS Council for International Organizations of Medical Sciences Council for International Organizations of Medical Sciences Established jointly by WHO and United Nations Educational, Scientific and Cultural Organisation (UNESCO) in 1949 Established jointly by WHO and United Nations Educational, Scientific and Cultural Organisation (UNESCO) in 1949 Guidelines on how to effectively apply the ethical principles as set forth in the DOH. Guidelines on how to effectively apply the ethical principles as set forth in the DOH.

42. © 2005 Aeras Global TB Vaccine Foundation 42 CIOMS Guidelines Consists of 15 guidelines that includes: Consists of 15 guidelines that includes: Informed consent Informed consent Standards for external review Standards for external review Recruitment of participants Recruitment of participants …….focuses on research sponsored by or initiated in developed countries and carried out in developing countries

43. © 2005 Aeras Global TB Vaccine Foundation 43 Do you recognise these elements? GCP and National Differences GCP is universal, but each country has its own regulations and agencies to ensure GCP compliance. GCP is universal, but each country has its own regulations and agencies to ensure GCP compliance. In the United States, GCP is implemented under 45 CFR Part 46, under the U.S. Code of Federal Regulations for the Protection of Human Subjects. In the United States, GCP is implemented under 45 CFR Part 46, under the U.S. Code of Federal Regulations for the Protection of Human Subjects. Defines the Institutional Review Board. Defines the Institutional Review Board. Provides guidelines for informed consent. Provides guidelines for informed consent. The U.S. 45 CFR Part 46 is only be applicable in South Africa if a study is U.S. funded or otherwise subject to U.S. regulations. The U.S. 45 CFR Part 46 is only be applicable in South Africa if a study is U.S. funded or otherwise subject to U.S. regulations.

44. © 2005 Aeras Global TB Vaccine Foundation 44 Clinical Trial Approval in SA Standard Approval Process: Standard Approval Process: 1. MCC (Regulatory Authority) 2. Ethics Committee Approval Multi-Centre Studies “It is unacceptable for developed country participants to have better standards of care offered in the study when compared to South African participants. When South Africa is chosen for a clinical trial while the trial is not undertaken in the country of origin an explanation should be sought about why this is the case.” SA GCP Guidelines “It is unacceptable for developed country participants to have better standards of care offered in the study when compared to South African participants. When South Africa is chosen for a clinical trial while the trial is not undertaken in the country of origin an explanation should be sought about why this is the case.” SA GCP Guidelines

45. © 2005 Aeras Global TB Vaccine Foundation 45 Documents that Guide the Conduct of Clinical Research in South Africa: Declaration of Helsinki -2000 Declaration of Helsinki -2000 ICH Guidelines for Good Clinical Practice (International Conference on Harmonization) ICH Guidelines for Good Clinical Practice (International Conference on Harmonization) CIOMS (Council for International Organizations of Medical Sciences) “International Guidelines for Biomedical Research Involving Human Subjects” – 1993 CIOMS (Council for International Organizations of Medical Sciences) “International Guidelines for Biomedical Research Involving Human Subjects” – 1993 These are the documents that ensure the welfare and integrity of participants in SA and must be followed by the principle investigator. “Guidelines for Good Practice in the conduct of Clinical Trials in Human Participants in South Africa” by the Dept.of Health

46. © 2005 Aeras Global TB Vaccine Foundation 46 Do We Have a SA GCP ? “Guidelines for Good Practice in the Conduct of Clinical Trials in Human Participants in South Africa” The purpose of these guidelines is to provide South Africa with clearly articulated standards of good clinical practice in research that are also relevant to local realities and contexts. The purpose of these guidelines is to provide South Africa with clearly articulated standards of good clinical practice in research that are also relevant to local realities and contexts.

47. © 2005 Aeras Global TB Vaccine Foundation 47 ACTIVITY

48. © 2005 Aeras Global TB Vaccine Foundation 48 How are Vulnerable Research Participants Protected? Some research participants are classified as Vulnerable Research Participants who are relatively or absolutely incapable of protecting their own interests. The research team should be aware of the special problems of research involving vulnerable populations The research team should be aware of the special problems of research involving vulnerable populations Is the Research Justified? Is the Research Justified? Must offer additional safeguards for their safety and welfare. Must offer additional safeguards for their safety and welfare.

49. © 2005 Aeras Global TB Vaccine Foundation 49 Special Populations of Participants 1. Children and Adolescents 2. Women and pregnancy 3. Pregnant Women 4. Fetuses in utero 5. Fetuses ex utero 6. Prisoners 7. Mental disability 8. Vulnerable communities 9. Other special Groups From the Guidelines for Good Practice in the conduct of clinical trials in Human Participant in South Africa. 2.3

50. © 2005 Aeras Global TB Vaccine Foundation 50 Some Specific Guidelines in Order to Further Protect….. Children and Adolescents Does not place the child in no greater than Minimal Risks Does not place the child in no greater than Minimal Risks If more than Minimal Risk - Direct Benefit for child If more than Minimal Risk - Direct Benefit for child Need Consent and Assent Need Consent and Assent

51. © 2005 Aeras Global TB Vaccine Foundation 51 Children in Research: Minors South African Law: Minor: Unmarried person below age 21 1 JULY 2007 CHANGED TO 18! The consent of a parent/legal guardian should be obtained for any research procedure involving a minor.

52. © 2005 Aeras Global TB Vaccine Foundation 52 Assent In Addition to Consent Out of Respect for Children/Adolescents as a developing person, children should be asked whether or not they wish to participate. Assent: A willingness that does not necessarily carry the greater understanding and legal implications that are generally understood by ‘consent’.

53. © 2005 Aeras Global TB Vaccine Foundation 53 Some Specific Guidelines In Order to Further Protect….. Vulnerable Communities Could this research not be carried out in populations from developed communities? Could this research not be carried out in populations from developed communities? The research must be responsive to the health needs and the priorities of the community. The research must be responsive to the health needs and the priorities of the community. Consent: content, languages and procedures Consent: content, languages and procedures Should not adversely affect the routine treatment of patients. Should not adversely affect the routine treatment of patients.

54. © 2005 Aeras Global TB Vaccine Foundation 54 Ongoing Protection Throughout the Study As researcher/team we now have: Approval of the study Approval of the study Signed consent document Signed consent documentBut In clinical research, the commitment to participants is to safeguard their interests throughout the study.

55. © 2005 Aeras Global TB Vaccine Foundation 55 Four Primary Means of Participant Protection Methods to protect our participants: 1. Ongoing Informed Consent 2. Safety Reporting 3. Data and Safety Monitoring 4. Continuing IRB Review

56. © 2005 Aeras Global TB Vaccine Foundation 56 1: Ongoing Informed Consent Informed consent is an ongoing communication process during the entire study. Informed consent is an ongoing communication process during the entire study. The participant should maintain the ability to understand and that he/she may withdraw from the study at any time. The participant should maintain the ability to understand and that he/she may withdraw from the study at any time. Additional Informed Consent (re-consent) should occur when: Additional Informed Consent (re-consent) should occur when: There are changes in the study There are changes in the study There is new information that may affect the willingness to participate further. There is new information that may affect the willingness to participate further.

57. © 2005 Aeras Global TB Vaccine Foundation 57 2: Safety Reporting Further ongoing protection of our participants is to report on any ill “effect” of our intervention/drug on our participants. Further ongoing protection of our participants is to report on any ill “effect” of our intervention/drug on our participants. We call this Adverse Event reporting. We call this Adverse Event reporting. The process will be detailed in the study protocol. The process will be detailed in the study protocol.

58. © 2005 Aeras Global TB Vaccine Foundation 58 Adverse Event (AE) “Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.” (ICH GCP 1.2)

59. © 2005 Aeras Global TB Vaccine Foundation 59 Adverse Drug Reaction (ADR) “All noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions.” (ICH GCP 1.1) Expected: Previously observed events Unexpected: Any AE that is not expected

60. © 2005 Aeras Global TB Vaccine Foundation 60 Serious Adverse Event (SAE) “Any untoward medical occurrence that at any dose: Results in death. Results in death. Is life-threatening. Is life-threatening. Requires inpatient hospitalization or prolongation of existing hospitalisation. Requires inpatient hospitalization or prolongation of existing hospitalisation. Results in persistent or significant disability/incapacity or Results in persistent or significant disability/incapacity or Is a congenital anomaly/birth defect.” (ICH GCP 1.50) Is a congenital anomaly/birth defect.” (ICH GCP 1.50)

61. © 2005 Aeras Global TB Vaccine Foundation 61 3: Data and Safety Monitoring Independent Committee Essential role : in protecting the safety of participants in protecting the safety of participants and ensuring integrity of the research study and ensuring integrity of the research study The Data Safety Monitoring Board (DSMB) can and will stop a study if: 1. There are safety concerns. 1. There are safety concerns. 2. The objectives of the study are met. 2. The objectives of the study are met. STOP

62. © 2005 Aeras Global TB Vaccine Foundation 62 4: Continuing IRB Review Annual Reports to the IRB from the regulatory officer of the study. Annual Reports to the IRB from the regulatory officer of the study. Reports from the DSMB. Reports from the DSMB. Depending on the degree of risk to participants - continuing review from the committee itself. Depending on the degree of risk to participants - continuing review from the committee itself.

63. © 2005 Aeras Global TB Vaccine Foundation 63 Finally.…. We now have: An understanding of what phase our trial is in An understanding of what phase our trial is in Approval for our study Approval for our study Signed Consent document Signed Consent document Ongoing protection right through our study Ongoing protection right through our studyRemember The Research Team has to ensure that the study is performed and the data are generated in compliance to GCP and the regulatory authorities.

64. © 2005 Aeras Global TB Vaccine Foundation 64 Review The Nuremberg Code was the first ethical code to provide us with some guidelines for “permissible medical experiments.” The Nuremberg Code was the first ethical code to provide us with some guidelines for “permissible medical experiments.” The Declaration of Helsinki provides additional guidelines especially relating to physicians conducting research with therapeutic intent on patients. The Declaration of Helsinki provides additional guidelines especially relating to physicians conducting research with therapeutic intent on patients. The Tuskegee Study led to the development of the Belmont Report. The Tuskegee Study led to the development of the Belmont Report. The three fundamental ethical principles that guide the ethical conduct of research are Respect for Persons, Beneficence and Justice. The three fundamental ethical principles that guide the ethical conduct of research are Respect for Persons, Beneficence and Justice.

65. © 2005 Aeras Global TB Vaccine Foundation 65 Review  Research conduct is further guided by the ICH GCP and the CIOMS guidelines.  The ICH GCP was initially developed to guide the ethics and standards for drug development and registration.  The CIOMS guidelines focus on research conducted in developing countries by developed countries.  “Guidelines for Good Practice in the conduct of Clinical Trials in Human Participants in South Africa.” is the document that provides SA with clear standards of GCP and incorporates the above mentioned guidelines.

66. © 2005 Aeras Global TB Vaccine Foundation 66 Review  There are specific guidelines that protects Children, Adolescents and Vulnerable communities even further and we must be aware of these guidelines.  In clinical research, the commitment to participants is to safeguard their interests throughout the study. This can be done with ongoing informed consent, safety reporting, continuing IRB review and safety monitoring.

67. © 2005 Aeras Global TB Vaccine Foundation 67 Review  Every drug trial has to go through the following Phases:  Phase I: “Is the treatment safe ?”  Phase II: “Can the treatment work ?”  Phase III: “Is the new treatment better than existing treatment or placebo?”  Phase IV: “Is there a better way to use this treatment ?”  The research team have to ensure that the research is performed and the data are generated in compliance to GCP and the regulatory authorities.

68. © 2005 Aeras Global TB Vaccine Foundation 68 Clinical Research Practice 2 This presentation is produced by Aeras Global TB Vaccine Foundation SM in collaboration with the University of Cape Town and the South African Tuberculosis Vaccine Initiative. A special thanks to Greg Hussey F.S.C.H., Tony Hawkridge, F.C.P.H.M., Hassan Mohammed, M. Med, Deon Minnies, Marie Buchanan, Hons.B.Soc.Sc, Marijke Geldenhuys, MSHS CRA, Sylvia Silver, D.A., Jen Page, M.Ed. for their contributions and support for this presentation.