1. Human Subjects Research Protection February 12, 2010 James Riddle, MCSE, CNE, CIP FHCRC Institutional Review Office https://centernet.fhcrc.org/CN/depts/iro/index.html History Principles and Regulations Institutional Review Boards Responsibilities of Investigators Informed Consent Privacy and Confidentiality Vulnerable Subjects Practical Implications

2. At FHCRC, you need human subjects training if… Design: developing the research concept, scientific method, and objectives that involve intervention with a human subject or the use of data or tissue derived from a human subject, or Conduct: implementation and management of research involving human subjects. Staff conducting research include principal investigators, research staff working on a research study, and others engaged in research activity supporting the research study (e.g., conducting interviews, surveys, data collection), or Reporting: analyzing, summarizing, or preparing manuscripts involving data derived from a research study involving human subjects. This training is good until February 11, 2013

3. 18 th C. 20 th C. 19 th C.

4. Nuremberg, 1946

5. THOSE NAZI DOCTORS DID HORRIBLE THINGS!! GOOD THING WE’RE NOT NAZIS!!

6. Willowbrook Hepatitis Study, 1956

7. Jewish Chronic Disease Hospital, 1963

8. PHS Syphilis Study, 1932-72

9. Dear Sir: Some time ago you were given a thorough examination and since that time we hope you have gotten a great deal of treatment for bad blood. You will now be given your last chance to get a second examination. 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 receive it. If you want this special examination and treatment you must meet the nurse at ____ on ____ __ at ____M. She will bring you to the Tuskegee Institute Hospital for this free treatment. We will be very busy when these examinations and treatments are being given, and will have lots of people to wait on. You will remember that you had to wait for some time when you had your last good examination, and we wish to let you know that because we expect to be so busy it may be necessary for you to remain in the hospital over one night. If this is necessary you will be furnished your meals and a bed, as well as the examination and treatment without cost. REMEMBER THIS IS YOUR LAST CHANCE FOR SPECIAL FREE TREATMENT. BE SURE TO MEET THE NURSE. Macon County Health Department

10. 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. REMEMBER THIS IS YOUR LAST CHANCE FOR SPECIAL FREE TREATMENT. BE SURE TO MEET THE NURSE.

12. 1.Respect for Persons Informed consent 2. Beneficence Risk/benefit assessment 3. Justice Selection of subjects

13. Theory… …and Practice FDA

14. Regulations Food and Drug Administration (FDA) –21 CFR Parts 50 & 56 Health and Human Services (HHS) – 45 CRF 46 (AKA: Common Rule) –Office of Human Research Protections (OHRP)

15. Clinical investigation means any experiment that involves a test article and one or more human subjects …. Human subject means an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient. 21 CFR 50.3 FDA What is “human subjects research”?

16. Who are “investigators”? Regulations – HHS -45 CFR part 46 (AKA: “Common Rule”) use the term “investigator” to refer to an individual performing various tasks related to the conduct of human subjects research activities: – Obtaining informed consent from subjects – Interacting with subjects – Communicating with the IRB. OHRP interprets an “investigator” to be any individual who is involved in conducting human subjects research studies. Such involvement would include: – Obtaining information about living individuals by intervening or interacting with them for research purposes; – Obtaining identifiable private information about living individuals for research purposes; – Obtaining the voluntary informed consent of individuals to be subjects in research; and – studying, interpreting, or analyzing identifiable private information or data for research purposes.

20. What is AAHRPP Founded in 2001 Responding to increased public concern for protecting research participants –seeks to ensure compliance with federal regulations –raise the bar in human research protection by helping organizations reach performance standards that surpass the threshold of state and federal requirements First institutions accredited in April 2003 FHCRC received accreditation in March 2008, one of approximately 80 institutions outside the VA to have their HRPP accredited.

21. Break…

22. Theory… …and Practice

23. 1. Full Committee Review 2. Expedited Review 3. Review for Exemption Status Levels of IRB Review (a dramatization) 4. Determination of “Not Human Subjects”

24. Criteria of IRB approval Risks to subjects are minimized by using procedures which are consistent with sound research design and resources which do not unnecessarily expose subjects to risk. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of knowledge that may reasonably be expected to result. Selection of subjects is equitable. Informed consent process and compensation will be sought from each prospective subject or the subject's legally authorized representative. Informed consent will be appropriately documented. Where appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects. Where appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data. Appropriate safeguards for special populations.

25. Categories of expedited review no IND or IDE blood sample collection specimen collection by noninvasive means data collection by noninvasive means materials collected for nonresearch purposes data from visual or audio recordings research on individual/group characteristics or behavior surveys, interviews, etc. continuing review of approved research, if no new subjects have been enrolled or new risks identified

26. Basic Elements of Informed Consent 1.A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental; 2.A description of any reasonably foreseeable risks or discomforts to the subject; 3.A description of any benefits to the subject or to others which may reasonably be expected from the research; 4.A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject; 5.A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained; 6.For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained; 7.An explanation of whom to contact for answers to pertinent questions about the research and research subjects’ rights, and whom to contact in the event of a research-related injury to the subject; and 8.A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.

27. Additional Elements of Informed Consent 1.A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable; 2.Anticipated circumstances under which the subject’s participation may be terminated by the investigator without regard to the subject's consent; 3.Any additional costs to the subject that may result from participation in the research; 4.The consequences of a subject’s decision to withdraw from the research and procedures for orderly termination of participation by the subject; 5.A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject; and 6.The approximate number of subjects involved in the study.

28. FHCRC Model consent (template)

29. IRB may waive/alter consent if… 1.The research involves no more than minimal risk to the subjects; 2.The waiver or alteration will not adversely affect the rights and welfare of the subjects; 3.The research could not practicably be carried out without the waiver or alteration; and 4.Whenever appropriate, the subjects will be provided with additional pertinent information after participation. 45 CFR 46.116(d)

30. Privacy Confidentiality T

31. Working with specimens/data Identifiability Gatekeeping Access Consent

32. OHRP Guidance on Research Involving Coded Private Information or Biological Specimens (10/16/2008) Obtaining identifiable private information or identifiable specimens for research purposes constitutes human subjects research. OHRP considers private information or specimens to be individually identifiable … when they can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems. Not human subjects research if: not collected specifically for the currently proposed research project through an interaction or intervention with living individuals cannot readily ascertain the identity of the individual

33. Vulnerable Working with Vulnerable Populations

34. Repositories How is consent obtained? How are specimens labeled (how identifiable?) Who is the gatekeeper of the repository? Are confidentiality pledges used to confirm that staff understand confidentiality obligations? How do you confirm each new study involving stored tissue receives IRB review and approval? QP

35. Emergency Treatment Regulations do not prohibit an investigator from using any investigational or approved drug/device in an emergency situation for patient clinical care. This use is not considered research. Prior IRB review and approval is required to consider the data as research. Q

36. Investigational New Drug (IND): 21 CFR 312 Investigational Device Exemption (IDE): 21 CFR 812 Q15

37. Practical Application A look at the FHCRC IRB Application Form

38. Practical Application Cancer Consortium Review System

39. Responsibilities of Investigators and the research team 6.Obtain informed consent in accord with the federal regulations and as approved by the IRB 10.Retain IRB research records and signed consent documents for at least 3 years past completion of the study 9.Report to the IRB any injuries, adverse events or other unanticipated problems involving risk to the participant 8.Report progress of the approved research to the IRB as often and in the manner prescribed by the IRB 7.Document the process Top 10

40. Responsibilities of Investigators and the research team. 1.Design and implement ethical research consistent with the three ethical principles outlined in the Belmont report Top 10 5.Implement the research as approved and obtain prior IRB approval of modifications 4.Comply with all applicable IRB policies, procedures and decisions 3.Ensure that all research involving human subjects is submitted to and approved by the appropriate IRB 2.Comply with all applicable federal regulations impacting the protection of human subjects

41. The success of clinical research lies on the element of trust – trust in researchers, trust in hospitals, and trust in the research process itself… Without trust at all of these levels, research could not be carried out. Potential subjects would be unwilling to put themselves in harm’s way if they perceived that they would be used by researchers, institutions, or those who fund research, and society at large would be unwilling to have its tax dollars spent on an enterprise that neither enjoyed nor deserved its trust. Kahn and Mastroianni, 2001

42. Thanks: Karen Hansen CITI Lee Hartwell Scientific Directors, FHCRC Protocol Office FDA Repositories Emergency treatment Questions? https://centernet.fhcrc.org/CN/depts/iro/index.html