Orientation for New Clinical Research PERSONNEL Module 1

1. Orientation for New Clinical Research PERSONNELModule 1 Presented by NC TraCS Institute UNC Office of Clinical Trials UNC Network of Clinical Research Professionals

2. Overview of orientation program & Introduction to clinical research Marie Rape, TraCS Regulatory Core

3. Overall Agenda for Orientation • Module 1: Introduction to Clinical Research, Education, and IRB • Module 2: Study Implementation, Documentation, and GCPs • Module 3: Contracting, COI, and Hospital Administrative Elements • Module 4: Clinical Trial Management, Budgeting, Hospital and Research Accounting

4. Module 1: Introduction and IRB • Overview of orientation program – Marie Rape • Introduction to clinical research – Marie Rape • UNC Network of Clinical Research Professionals, available educational programs – Michelle Duclos • OHRE and IRB overview – Tim Kuhn

5. Module 2: Study Implementation and Good Clinical Practices • Roles of research personnel, study implementation – Michelle Duclos • Good Clinical Practices (GCP) and study documentation – Marie Rape • Informed consent process, HIPAA – Claudia Christy

6. Module 3: Contracting and Hospital Administrative Elements • Conflicts of interest – Joy Bryde • Contracts and clinical trial agreements – Aylin Regulski • ClinicalTrial.gov and ICMJE requirements – Monica Coudurier • Investigational Drug Service – Sue Pope • Investigational Device Policy – Aylin Regulski

7. Module 4: Clinical Trial Management, Budgeting, and Accounting • Overview of the Clinical Research Management System (CRMS) – Ed Finerty/Laura Cowan • Hospital 98 accountsand research billing – Nancy Rose and Amelia Rountree • Budgeting and accounting of research funds – Jill Cunnup • Medicare coverage analysis – Jill Cunnup

8. Overall Objectives • Define human subject / clinical research • Discuss various options available for training of research personnel • Review human subject research protection and the IRB • Define appropriate responsibilities for study team members • Describe steps for successful implementation of a study • Describe appropriate management of study documentation • Define Good Clinical Practices (GCP) • Review the informed consent process • Discuss research compliance and required approvals at UNC • Review basic elements of contract negotiation and grant management • Review use of the Clinical Research Management System (CRMS) • Describe process for managing hospital research accounts and bills • Describe steps for managing budgets and accounting of funds

10. Who should attend Orientation? • Personnel involved in clinical (human) research • Study coordinator • Social/Clinical research assistant • Research nurse • Research associate • Regulatory personnel • Investigators • Involved in any type of clinical research • Social Behavioral research • Clinical trials • Investigator initiated research • Federal grants • Biomedical research

11. Definition of Clinical Research Clinical Research defined by NIHas • Patient-oriented research:research involves a particular person or group of people or uses materials from humans. • Studies of mechanisms of human disease • Studies of therapies or interventions for disease • Clinical trials • Studies to develop new technology related to disease • Epidemiological and behavioral studies:studies examine distribution of disease, factors that affect health, how people make health-related decisions. • Outcomes and health services research:studies seek to identify the most effective and most efficient interventions, treatments, and services.

12. Conducting Quality Research • The overarching objective of clinical research is to develop generalizable knowledge to improve health and/or increase understanding of human biology • However, research asking socially valuable questions can be designed or conducted poorlyleading to scientifically unreliable or invalid results. Study personnel are key to conducting quality research! • Knowledge of research best practices, good clinical practices, keeping abreast of regulatory requirements, and training needs are key to conducting quality research.

13. Knowing the Resources Available

14. Training, Training, Training Training is key to keeping abreast of best practices and regulatory requirements. You need to take responsibility for staying informed and educated! Pre-Requisites for Orientation • Completion of CITI Good Clinical Practice (GCP) Online Training, available at www.citiprogram.org • Completion of CITI Ethics Online Course, available at www.citiprogram.org

15. Study Coordinator Education Michelle Duclos, President NCRP

16. Why Coordinator Education? The investigator should ensure that any individual to whom a task is delegated is qualified by education, training and experience (and state licensure where relevant) to perform the delegated task. Documentation of training is essential for meeting the guidelines put forth by regulatory agencies for the conduct of Human Subject Research.

17. Study Coordinator Education • Documentation of Coordinator Education may be part of the investigator/ department/division/center processes. This may include (dependent on type of research being conducted) • Completion of Human Research Ethics Training • Completion of Good Clinical Practices Training • CV and/or state licensure • Job Skill Training (such as conducting an EKG) • Training plan per your specific job title • Documentation of Training for each protocol

18. Example Training/Education Checklist

19. Example Matrix of Training

20. Study Coordinator Education OHRP – Office of Human Research Protection • Responsibilities of UNC • Before any human subjects research can be conducted, the institution must provide the department or agency a written Assurance that it will comply with the requirements of the Policy • www.hhs.gov/orhp • The HHS regulations are intended to implement the basic ethical principals governing the conduct of human subject research • General Responsibilities • All parties involved, institution, investigator, and IRB must actively engage in ensuring human subject protection and this is only achieved through proper training/education of all research professionals

21. The purpose of the UNC-NCRP is to promote excellence in the conduct of clinical, social, behavioral, and translational research through a forum of education, professional development and mentoring programs

22. NCRP Educational Programs • Lunch and Learns/Educational Seminars • Mentoring • Certification • Committees • Best practices • Education • Mentoring • Listserv –

23. Current Projects • Developing a career ladder with Office of Vice Chancellor for Research • Developing a coordinator handbook – release date Oct 2012 • Organizing ACRP/SoCra Certification study groups - ongoing • Working towards developing a social/behavioral research coordinator handbook • Developing a Recruitment Toolkit to be available on website • Developing SOPS and best practices, available on website – release date Oct 2012 • Education through DID YOU KNOW series sent out via list serv • Increasing awareness of NCRP • NCPR wants to help you! Please let us know what you need to do your job better!

24. Upcoming Training: Go to: http://tracs.unc.edu/clinical-research/education-sessions.html For a list of upcoming NCRP Education Sessions. CEUs may be offered for select programs.

25. Who to Contact • To join the list serv, contact Michelle Duclos at mduclos@med.unc.edu • To serve on a committee, contact the committee chair • Information regarding committees and upcoming events can be found on our web site – www.uncncrp.org

26. IRB Overview Tim Kuhn IRB Training Coordinator Office of Human Research Ethics

27. Objectives • List three types of IRB review • Describe two IRB-related responsibilities for investigators after receiving IRB approval for a study • Describe which Events ARE reportable to the UNC IRB • State what the UNC-CH IRB requires for ethics training • Update on On-line IRB submissions • Questions

28. ohre.unc.edu • Regulatory Documents: OHRE Standard Operating Procedures (SOPs); IRB Rosters • For Researchers: Submission Instructions; Frequently Asked Questions (FAQs); Student Guidance • Deadlines and Meeting Dates • Access to Ethics Training (CITI: Human Subjects Protection “IRB” Modules) • On-Line Submissions: Web portal for reporting UPs/AEs; On-line Application; On-line Submission FAQs; Training Videos and Printable Aids • Resources: Links to useful information

29. US REGULATORY REQUIREMENTS • All human subjects research must have prior approval by an Institutional Review Board • Independent review to protect rights and welfare of subjects • Informed consent must be obtained (unless waived by the IRB) • An “Assurance” to the federal government binds UNC-Chapel Hill to uphold ethical and regulatory requirements • License to receive extramural grants • Can be suspended for violations

30. What is Research? • Federal Regulations define Research as a systematic investigation designed to develop or contribute to generalizableknowledge • Innovative clinical care is not necessarily research • QA/QI is not necessarily research

31. WHAT IS A HUMAN SUBJECT? • Federal Regulations define a human subject as a living individual about whom an investigator obtains... • data through interaction or intervention • randomized clinical trial • exposure to controlled conditions • systematic gathering of physiologic or psychological data • identifiable private information • medical records review • study of existing biologic specimens

32. Compulsive Buying Patterns in College Students • Who: Undergraduate students • What: surveys of self esteem and buying habits • When: class time (tacked on at the end) • Where: recruited through university classes • Why: assess prevalence of compulsive buying, measure habits against low self esteem measures

33. Additional details: • Questionnaire includes questions about drug and alcohol use (current and past) • Consent form requests signature • PI requests an “exemption”

34. What is an IRB? (Institutional Review Board) • A committee mandated by federal regulations. • Protects the rights and welfare of human subjects in research activities through independent review of proposed research.

35. What does an IRB do? • Educates researchers about the IRB review process and requirements • Approve, disapprove or modify research involving human subjects • Conduct continuing review of research • Observe, monitor, audit research • Suspend or terminate approval of research

36. IRB Membership • At least 5 members, not all men, not all women (UNC IRBs have 10-15 members) • Not all members of one profession • Diversity • Expertise appropriate to the research • At least one scientist, one non-scientist • At least one member not otherwise affiliated with the institution

37. UNC-CH IRBs • Biomedical (A,B,C,D): Expertise is focused on medical, dental, surgical, physiological, or pharmacological research • Non-Biomedical (E): Expertise is focused on research in behavioral and social sciences; the humanities; and research in a public health or nursing context

38. Growth in Volume and Complexity of Research Requiring IRB Review1999-2011

39. Full Board Review Minimal Risk? Expedited Is it on the list? 9 Categories defined by Regs Is it on the list? 6 Categories defined by Regs “Exempt” 2. Are there Human Subjects? Not Human Subjects Research 1. Is it Research? RISK Level of Risk Generally Determines Level of IRB Review

40. Types of Risk • Physical (e.g. pain, drug side effects, or injury) • Psychological (e.g. emotional distress) • Social (e.g. stigmatization) • Economic (e.g. loss of job—breach of confidentiality that relates to stigma, or workplace competency issues) • Legal (requirements to report some illegal activities, whether the focus of the study, or which emerge without prompting)

41. “Exempt” Research45 CFR 46.101(b) • Six categories, defined by regulations • PI may request an exemption • IRB will make the determination • Exempt from continuing review, once approved by the IRB • Investigator obligated to conduct research as described in protocol

42. “Exempt” Research*45 CFR 46.101(b) 1. Normal educational practices in established educational settings 2. Educational tests, surveys, interviews, or observation of public behavior -unless identified & sensitive** 3. Research on elected or appointed public officials or candidates for public office * Exception for prisoners ** Exception for children 4. Research using existing data, if publicly available or recorded without identifiers 5. Evaluation of public benefit service programs 6. Taste and food quality evaluation and consumer acceptance studies

43. Expedited Review45 CFR 46.110 • Nine categories, defined by regulations • Chair or designated member • IRB Members informed • Reviewer may not disapprove

44. Criteria for IRB Approval:Expedited or Full Board review • Risks minimized • Favorable risk: benefit ratio • Equitable selection of subjects • Informed consent sought • Informed consent documented • Monitoring plan for safety • Privacy and confidentiality protected • Additional safeguards for vulnerable populations 45 CFR 46.111 and 21 CFR 56.111

45. The IRB MeetingVoting on possible actions

46. When You Get a Contingency Memo: • Don’t despair and don’t take it personally • It is rare for study not to raise at least one question from the IRB • The PI should respond point by point in writing to the memo and make the corresponding changes to the application and consent forms

47. When You Get a Contingency Memo:

48. Approved! • Research may proceed upon receipt of written documentation of IRB approval • Investigator has a responsibility to report to the IRB • Changes BEFORE they are implemented • Unanticipated problems or serious adverse events that may occur during the research

49. What if you want to change the protocol? • Once your study is approved, you may submit modifications • All protocol changes must be approved by the IRB before implementation. • All changes to documents used with subjects (consent forms, questionnaires, recruitment materials, etc.) must be approved by the IRB before using.

50. Modifications to Approved Studies • The IRB assesses if the modification changes the level of risk: • Do subjects need to be made aware of the new information? • If a revised consent form is included, is it accurate?