1. © 2004 1 Clinical Research Practice Clinical Research Organization and Management 1

2. 22 Objectives Describe the life cycle of clinical research. Describe the life cycle of clinical research. Differentiate between clinical research and other types of research. Differentiate between clinical research and other types of research. Outline how a clinical research team is organized. Outline how a clinical research team is organized. State the roles and responsibilities of: State the roles and responsibilities of: Sponsor Sponsor Principal Investigator Principal Investigator Institutional Review Board (IRB) or Institutional Ethics Committee (IEC) Institutional Review Board (IRB) or Institutional Ethics Committee (IEC) Medicines Control Council (MCC) Medicines Control Council (MCC) Monitors Monitors Auditors Auditors SANAS SANAS Community Community

3. 33 Objectives Differentiate between the three levels of responsibility on the clinical research team. Differentiate between the three levels of responsibility on the clinical research team. Explain how your particular position supports the overall goals of a clinical research project that you are currently working on. Explain how your particular position supports the overall goals of a clinical research project that you are currently working on.

4. 44 What Do You Already Know About Clinical Research? Research performed primarily on humans. Research performed primarily on humans. Designed to answer specific questions related to human disease interventions such as diagnosis, prevention, outcomes and treatments. Designed to answer specific questions related to human disease interventions such as diagnosis, prevention, outcomes and treatments. Performed according to ICH ethical guidelines and GCP/GLP. Performed according to ICH ethical guidelines and GCP/GLP. And … it is what we are here to do every day. And … it is what we are here to do every day.

5. 55 Is All Research Clinical? No! Not all research deals with disease intervention and may not include human participants. No! Not all research deals with disease intervention and may not include human participants. Research may be conducted on animals. Research may be conducted on animals. Research may not be focused on an intervention, but rather look for existence of disease. Research may not be focused on an intervention, but rather look for existence of disease. Can you think of any studies you have worked on that are NOT clinical research?

6. 66 You Know It Is Clinical Research If… It encompass at least one of the following categories: It encompass at least one of the following categories: Human participation Human participation Record based studies Record based studies Clinical samples Clinical samples Technology development for clinical use Technology development for clinical use (according to the Medical Research Council of South Africa guidelines, 2004)

7. 77 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

8. 88 Clinical Research Components Principal Investigator & Research Team

9. 99 Clinical Research Components Principal Investigator & Research Team

10. 10 Sponsor Responsible for: trial initiation trial initiation oversight of the study oversight of the study financing all activities financing all activities The sponsor is the organization that supports the clinical trial and ensures it will occur.

11. 11 Clinical Research Components Principal Investigator & Research Team

12. 12 Principal Investigator & Research Team The Principal Investigator (PI) runs the clinical trial at the trial site. The PI may designate a research team to carry out these duties. Responsible for: Compliance to GCP and ICH guidelines. Compliance to GCP and ICH guidelines. Ensures adequate resources and qualified team trained on protocol is in place. Ensures adequate resources and qualified team trained on protocol is in place. Medical care of trial participants. Medical care of trial participants. Accountable for investigational products. Accountable for investigational products. Produce safety reports and other documentation. Produce safety reports and other documentation.

13. 13 Research Team & Site Organization Designing and implementing a clinical trial requires the many talents of a multidisciplinary research team. Designing and implementing a clinical trial requires the many talents of a multidisciplinary research team. Each team may be set up differently, depending on an institution's policy and resources. Each team may be set up differently, depending on an institution's policy and resources.

14. 14 Organization of RCT Study Regulatory Officer ChiefMedical Officer Chief Medical Officer Principal Investigator Data Manager Clinical Operations Manager Administrative Manager Laboratory Manager Data Capturer Nurse Coordinator Research Nurses Community Health Workers Research Assistants Medical Technologists Scientific Officers Admin. Officer Support Staff Internal Monitor

15. How Do You Contribute To The Study Goals? Enroll & Consent Participants Gather Information (conduct tests and collect specimens) Test Specimens Record Participant Data Compile & Analyse Data Study Results Monitor Activities and Ensure Compliance Prepare Site

16. 16 Who is the Clinical Research Team? Three classifications within Clinical Research Practice have been proposed: Clinical Research Manager e.g. Operations Manager. Clinical Research Manager e.g. Operations Manager. Clinical Research Officer e.g. Nurse Co- ordinator. Clinical Research Officer e.g. Nurse Co- ordinator. Clinical Research Assistant e.g. Research Nurse Assistant. Clinical Research Assistant e.g. Research Nurse Assistant.

17. 17 Provide overall management of study activities and primary supervision of staff. Provide overall management of study activities and primary supervision of staff. Implement and maintain trial systems toward the achievement of the clinical trial goals. Implement and maintain trial systems toward the achievement of the clinical trial goals. Collate and report study data. Collate and report study data. Manage and consult on budget issues. Manage and consult on budget issues. Provide leadership in setting and achieving long-term goals and objectives. Provide leadership in setting and achieving long-term goals and objectives. Coordinate activities between clinical, laboratory, data management and other aspects of the clinical trial. Coordinate activities between clinical, laboratory, data management and other aspects of the clinical trial. Clinical Research Manager

18. 18 Clinical Research Officer Supervise specific clinical/technical functions within clinical research. Supervise specific clinical/technical functions within clinical research. Responsible for the confirmation of the integrity of the clinical and demographic data. Responsible for the confirmation of the integrity of the clinical and demographic data. Monitor the proper and efficient utilization of study materials. Monitor the proper and efficient utilization of study materials. Oversee the clinical research outcomes. Oversee the clinical research outcomes. Have roles related to the clinical, laboratory or data management arms of clinical research. Have roles related to the clinical, laboratory or data management arms of clinical research.

19. 19 Clinical Research Assistant: Assist in the performance of clinical, laboratory, data management and other aspects of clinical research. Assist in the performance of clinical, laboratory, data management and other aspects of clinical research. Have roles related to the clinical, laboratory or data management arms of clinical research. Have roles related to the clinical, laboratory or data management arms of clinical research.

20. 20 Clinical Research Components Principal Investigator & Research Team

21. 21 Institutional Review Board (IRB) or Institutional Ethics Committee (IEC) An independent body of medical, scientific and non-scientific members that ensures the protection of the rights, safety and well-being of human subjects involved in a trial. Responsible for: Review of trial protocol and recruitment, consent information, etc Review of trial protocol and recruitment, consent information, etc Retain documents for regulatory authority. Retain documents for regulatory authority.

22. 22 Clinical Research Components Principal Investigator & Research Team

23. 23 Medicines Control Council (MCC) MCC is South Africa’s government authority to oversee the regulation of medicines to ensure the safety, quality and efficacy of available drugs. Responsible for: Reviewing proposed clinical trials in South Africa. Reviewing proposed clinical trials in South Africa. Approving clinical trials that meet regulations. Approving clinical trials that meet regulations.

24. 24 Clinical Research Components Principal Investigator & Research Team

25. 25 Monitors Monitors are internal and external people appointed by the sponsor to verify that the trial is conducted appropriately. Responsible for: Examining protocol, SOP’s, and other documentation. Examining protocol, SOP’s, and other documentation. Reviewing documentation and conduct of trial for compliance to GCP and other regulations. Reviewing documentation and conduct of trial for compliance to GCP and other regulations. Verify that data is accurate and participant rights and well-being are protected. Verify that data is accurate and participant rights and well-being are protected.

26. 26 Clinical Research Components Principal Investigator & Research Team

27. 27 Auditors The auditors are independent individuals appointed by the Sponsor to conduct a systematic and in-depth examination of trial conduct and compliance. Auditors are separate from monitors and quality control. Responsible for: Reviewing activities and documentation to check that the protocol, SOPs, GCP, GLP and applicable regulatory requirements are followed. Reviewing activities and documentation to check that the protocol, SOPs, GCP, GLP and applicable regulatory requirements are followed.

28. 28 Why Is Auditing Important? An audit is an examination of data, records, and written procedures to determine accuracy and completeness of the research process and maintenance of current regulatory documentation. An audit is an examination of data, records, and written procedures to determine accuracy and completeness of the research process and maintenance of current regulatory documentation. The audit provides information to the site staff and Sponsor that verifies the accuracy and reliability of clinical trials data and results. The audit provides information to the site staff and Sponsor that verifies the accuracy and reliability of clinical trials data and results.

29. 29 Clinical Research Components Principal Investigator & Research Team

30. 30 SANAS The South African National Accreditation System (SANAS) is the body that gives formal recognition that test facilities are competent to carry out specific tasks. Responsible for: Inspecting facilities to ensure compliance to OECD GLP principles. Inspecting facilities to ensure compliance to OECD GLP principles.

31. 31 Clinical Research Components Principal Investigator & Research Team

32. 32 Community The community where clinical research is performed is involved through a Community Advisory Board that takes an active role in research activities and is kept up-to-date on study activities. Responsible for: Providing insight into the needs of the community. Providing insight into the needs of the community. Promoting community awareness of the study. Promoting community awareness of the study. Playing an active role in safeguarding the community rights. Playing an active role in safeguarding the community rights.

33. 33 Review Clinical research is a process that seeks to find the answer to a question about a health intervention. Clinical research is a process that seeks to find the answer to a question about a health intervention. Clinical research is performed primarily on humans with the hope of resulting in new or improved health interventions. Clinical research is performed primarily on humans with the hope of resulting in new or improved health interventions.

34. 34 Review Clinical Research is organized with a variety of oversight committees and regulatory bodies to ensure respect and safety for human participants, including: Clinical Research is organized with a variety of oversight committees and regulatory bodies to ensure respect and safety for human participants, including: Sponsor Sponsor Principal Investigator Principal Investigator IRB/IEC IRB/IEC Community Community Medicines Control Council (MCC) Medicines Control Council (MCC) SANAS SANAS Monitors Monitors Auditors Auditors

35. 35 Clinical Research Components Principal Investigator & Research Team

36. 36 Review Each clinical research site has common jobs and responsibilities, but may be organized differently. Each clinical research site has common jobs and responsibilities, but may be organized differently. The organization of clinical research at UCT is unique to UCT. The organization of clinical research at UCT is unique to UCT. Everyone on the team contributes to the goals and ultimate success of the clinical research. Everyone on the team contributes to the goals and ultimate success of the clinical research.

37. 37 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 Professor Greg Hussey, Deon Minnies, Lucrecia Michaels, Marie Buchanan, Marijke Geldenhuys, MSHS CRA, Marwou De Kock, B.Tec., Dr. Sylvia Silver, D.A., and Jen Page, M.Ed. for their contributions and support for this presentation. Clinical Research Organization and Management 1