1. IRB Refresher 2009 Helen Panageas Associate Director NYU School of Medicine INSTITUTIONAL REVIEW BOARD Kim Diccianni Senior Education Coordinator www.med.nyu.edu/irb

3. Thank you for joining us. We hope to enhance your thinking as an IRB Member by refreshing your knowledge of Federal Regulations and NYU SoM IRB Policies.

4. Goals Conflict of Interest Conflict of Interest (presented by Office of Research Compliance) International Research International Research Genetic Research Genetic Research GINA GINA Data and Tissue Repositories Data and Tissue Repositories *NEW* Capacity to Consent Policy *NEW* Capacity to Consent Policy Informed Consent Process Informed Consent Process 111 Findings 111 Findings

5. Policies on Conflicts of Interest, Consulting and Commitment PART 2: RESEARCH CONFLICTS OF INTEREST IRB Training Sessions April 30, 2009 Created by Monique Phillips

6. Part 2: Research Conflicts of Interest Consists of two policies: Policy on Conflicts of Interest in Research and Sponsored Programs - Replaces the Investigator Financial Interest Disclosure and Conflict of Interest Policy dated October 1, 1995 Policy on Institutional Conflicts of Interest in Human Subjects Research

7. Policy on Conflicts of Interest in Research and Sponsored Programs What’s the Purpose of the Policy? To conduct research that is free of any appearance of impropriety or Conflict of Interest (research integrity) To protect: Human and Non-Human Subjects Reputation of NYU Langone Medical Center and NYU SoM What’s the General Policy? All persons involved in a Sponsored Research Project must disclose their financial interest If a financial interest exists, it must be evaluated, and managed or eliminated

8. Who Needs to Disclose Under this Policy? All persons involved in the Sponsored Project must disclose their financial interest: Investigators Program Directors Key Personnel (e.g. study coordinator, outside collaborator) When Do Disclosures Need to be Made? Annually (Annual Disclosure Form) – except outside collaborators With each initial protocol submission When submitting annual protocol continuations Before obtaining a new financial interest

9. What Kinds of Things Need to Be Disclosed? Outside Positions (Paid or Unpaid) Director, Trustee, Senior Executive, Officer or Employee Ownership Interests (Any dollar amount) Stock or stock options Consulting Compensation Consulting fee, honoraria/lecture fees, or other payment Royalty Income Intellectual Property Rights (Patent, license, or copyright)

10. Who Determines if a Financial Interest is Considered a Conflict of Interest? All financial interests related to a study (i.e. outside positions, consulting and other compensation, IP) should be disclosed The CMU and/or RCOIC will determine if a conflict of interest exists

11. When is a Conflict of Interest Considered Manageable vs. Unmanageable? Financial Interests (not significant) Participation is generally permitted with a conflict management plan issued by the CMU on behalf of the RCOIC Significant Financial Interests Participation is not permitted unless the RCOIC determines that “Compelling Circumstances” exist A conflict management plan is implemented if participation is permitted Appeals are made to the SVP and Vice Dean for Science

12. Review Thresholds: Human Subjects Interest TypeFinancial Interest Significant Financial Interest Outside Position Ownership Interest Consulting Compensation (in 1 yr.) $1-$10,000$10,001+ Royalty Income$1-$10,000$10,001+ Intellectual Property

13. Review Thresholds: Non-Human Subjects (Pre-Clinical) Interest TypeFinancial Interest Significant Financial Interest Outside Position Ownership Interest Consulting Compensation (in 1 yr.) $1-$10,000$10,001+ Royalty Income$1-$10,000$10,001+ Intellectual PropertyN/A

14. Review Thresholds: Non-Human Subjects Interest TypeFinancial Interest Significant Financial Interest Outside Position Ownership Interest Publicly Traded Privately-Held $25,001+ Consulting Compensation (in 1 yr.) $1-$25,000$25,001+ Royalty Income$1-$25,000$25,001+ Intellectual PropertyN/A

15. Policy on Institutional Conflicts of Interest in Human Subjects Research What’s the Purpose of this Policy? To remove the appearance of inappropriate influence over the integrity of a research project and to ensure the safety and care of the human subjects enrolled in the study in cases where the Medical Center: Receives or expects to receive royalty income from the sale of a product covered by a patent, license or copyright Holds or proposes to hold any equity interests of any amount in the sponsor of the research study What is the General Policy? The Medical Center will not participate in a human subject’s research project when it has an institutional conflict of interest, unless the RCOIC determines Compelling Circumstances exist to warrant an exception Appeals are made to the SVP and Vice Dean for Science

16. Individual vs. Institutional COIs: What is the RCOIC Process? RCOIC Review & Evaluation – Individual Conflicts Review SFI matters to determine if “Compelling Circumstances” exist to justify an Investigator’s participation Propose and approve a conflicts management plan for those matters where an Investigator’s participation is permitted in the Sponsored Project RCOIC Review & Evaluation – Institutional COIs Review of Institutional COI matters to determine if “Compelling Circumstances exist to justify the Medical Center’s participation Propose and approve a conflicts management plan for those matters where the Medical Center’s participation is permitted in a project

17. Compelling Circumstances Test Factors for Determining if “Compelling Circumstances” Exist: Is the research appropriate and fundamental to the Medical Center? Can the nature and amount of the financial interest significantly influence the outcome of the research? Is this specific research essential to the continuity of the overall research? Does the investigator have a unique expertise that is essential to the study? Should there be any restrictions placed on publications or presentations related to this research? Are there minimal risks to the subjects?

18. Compelling Circumstances Test (Cont’d.) Factors for Determining if “Compelling Circumstances” Exist: For multicenter studies, is the %age of the total number of subjects so minimal as not to significantly impact the outcome of the study? What are the proposed steps for oversight and management of the financial interests? What role do the students/ trainees/ junior faculty and staff play? Are their roles free from exploitation and appropriate to the study? For Institutional COIs: Is the Medical Center uniquely qualified to conduct the research (i.e. special facilities or equipment, unique patient population, qualifications of its investigators)

19. CMU Review & Evaluation What is the CMU’s role? Disclosures with no financial interest Sponsored Projects where a Financial Interest (not SFI) is disclosed The CMU makes a determination on behalf of the RCOIC Initial evaluation of disclosures with a Significant Financial Interest The CMU passes these matters onto the RCOIC for final determination Sponsored Projects that have been previously, evaluated, and given a conflict management plan

20. RCOIC vs. the IRB RCOIC Reviews SFI matters and all other matters referred by the CMU Review and evaluation must be completed by the RCOIC for all SFI matters before the IRB can give approval Determines if Compelling Circumstances exist Adopts management plans for matters where Compelling Circumstances exist IRB Cannot approve protocols referred to the RCOIC without the RCOIC’s approval recommendation (management plan) May modify the RCOIC’s management plan to impose more stringent restrictions Final approval for a study must come from the IRB

21. Changes from Existing Policy Research Disclosure integrated w/Annual Disclosure Investigator Disclosure Forms to be electronically submitted & searchable within the next 12 months Increased requirements for Financial Interest Disclosure, especially NYU IP rights CMU does initial review & in some cases issues a determination on behalf of RCOIC Clearer instructions and mandates for RCOIC Implementation of Compelling Circumstances Test for RCOIC members Responsibilities of Vice Dean for Science more apparent New Institutional COI Policy outlines policy & process Dedicated website for further guidance and resources

22. Conflicts Management Unit (CMU) Website Highlights Resource center for RCOIC Members Agenda Meeting Schedule Meeting materials RCOIC Operating Guidelines Full and abbreviated versions of Policies Provides examples of conflicts in research, case studies and other useful tools for further guidance CMU Website: http://cmu.med.nyu.edu

23. What is International Research Research conducted by University investigators/faculty in foreign countries

24. How should the IRB review International Research… As rigorously as if the project was being completed at NYU SoM/Medical Center and its affiliates As rigorously as if the project was being completed at NYU SoM/Medical Center and its affiliates US rules prevail over US research being completed in another country. US rules prevail over US research being completed in another country. Authorization required as per HIPAA Authorization required as per HIPAA Informed Consent or Waiver required Informed Consent or Waiver required 111 findings must be made 111 findings must be made Research study should have been or will be reviewed by the country’s research ethics review board or equivalent. Research study should have been or will be reviewed by the country’s research ethics review board or equivalent.

25. Submission Materials In addition to all the usual IRB submission materials, the Researchers should provide: Local review and documentation of the review and approval If federal funding supports the research, the international site is considered ‘engaged ‘in the research  IRB approval from an institution with an FWA (in that country) is required Provisions regarding how risks will be minimized for the subjects Consent Process/Documentation Plan Illiteracy, native language consent forms, verbal consent etc.

26. Consider the Research Methods to be used What recruitment methods will be used? Do those methods violate cultural norms of confidentiality? Does the collection data or specimens involve sensitive, identifiable information? How experienced is the PI in doing research in that country?

27. How about Informed Consent… Are there important historical or cultural considerations? Who will be doing the actual consent process? Consent documentation: Translation – not just words, but culturally- appropriate concepts – e.g., explaining randomization in terms of a lottery Is a written form appropriate? Signature requirements

28. Do we have enough Knowledge of Local Research Context? Ways for lead IRB to obtain knowledge of local research context: knowledgeable IRB member consultants:   US faculty member   foreign IRB member   other individual

29. How Can an IRB Obtain Knowledge of Local Research Context? Personal knowledge of an IRB member Personal knowledge of an IRB member Prior written review by a consultant Prior written review by a consultant Participation by a consultant at an IRB meeting (in person or by teleconference) Participation by a consultant at an IRB meeting (in person or by teleconference) Systematic, reciprocal exchange: Systematic, reciprocal exchange: Site visits Site visits Interaction with consultant Interaction with consultant Interaction with institutional liaisons Interaction with institutional liaisons Review of relevant written materials Review of relevant written materials Source: OHRP: IRB Knowledge of Local Research Context, July 21, 2000

30. Other IRB Considerations… Consider the principles outlined in the Belmont Report Consider the principles outlined in the Belmont Report If there is no equivalent human subject protection board If there is no equivalent human subject protection board or group, investigators must rely on local experts or community leaders to provide approval. The IRB requires documentation of this "local approval" before it gives approval. investigators must rely on local experts or community leaders to provide approval. The IRB requires documentation of this "local approval" before it gives approval.

31. Hypothetical Survey: IRB Relationships NYU SoM Lead IRB England Local IRB #1 Poland Local IRB #2 Belarus Currently has no IRB established

32. Coordinating the Role of IRBs Clarify the roles of the lead vs. local IRBs areas of responsibility? resolution of conflicts? initial vs. continuing review? Other? Define working relationships – possible approaches: do joint reviews by primary reviewers foreign IRB member serve as consultant to US IRB (and vice versa)

33. What about Belarus? Options: Establish a new IRB in Belarus Identify an existing IRB in a nearby country with appropriate knowledge of local research context – Polish IRB? Rely on the NYU SoM IRB, if it can obtain knowledge of local research context

34. Resources Reports and Articles Policy Issues in International Research: Clinical Trials in Developing Countries April 2001 Report and Recommendations of the National Bioethics Advisory Commission (NBAC) Policy Issues in International Research: Clinical Trials in Developing Countries Ethics of Clinical Research in the Developing World Mar. 2002 Nature Reviews Immunology Ethics of Clinical Research in the Developing World International Ethical Guidelines for Biomedical Research Involving Human Subjects Oct. 2002 by the Council for International Organizations of Medical Sciences International Ethical Guidelines for Biomedical Research Involving Human Subjects Report: The ethics of research related to healthcare in developing countries 24 April 2002 Report: The ethics of research related to healthcare in developing countries International Compilation of Human Research Protections 2009 Edition Compiled By: Office for Human Research Protections, U.S. Department of Health and Human Services

35. Genetic Research

36. What is Genetics Research? Genetic research involves the analysis of any of the following: DNA, RNA, chromosomes, proteins, or certain metabolites which might act as or identify markers associated with a known or suspected predisposition to disease or behavior. Usually genetic research involves the collection of human biological material such as blood, skin or other tissues, nail clippings or hair. Genetic research also may include the construction of pedigrees (maps of the distribution of a particular trait or condition among related individuals) or family medical histories.

37. The potential power of genetic research is also the inherent risk such as: Patients and family members learn of ominous mutations prior to disease symptoms. Genetic information, not specifically solicited by the subject, could be the first warning sign of a troubled future. Genetic Research Mutations can be carried through subsequent generations, affecting as yet unborn descendants; and potential illness can be predicted even for family members, un-enrolled and unaffiliated with the research protocol. Un-validated results of genetic experiments can still cause actual psycho-social hardship even leading to financial loss.

38. What is considered genetic information? Information about: A person’s genetic tests (defined in the NY State Law as any laboratory test of human DNA, chromosomes, genes, or gene products to diagnose the presence of a genetic variation linked to a predisposition to a genetic disease or disability in the individual or individual's offspring; such term shall also include DNA profile analysis) Genetic tests of a person’s family members Disease or disorder in a family member Participation of a person or family member in research that includes genetic testing, counseling, or education

39. What is considered genetic information? Tests for BRCA1/BRCA2 (breast cancer) or HNPCC (colon cancer) mutations Classifications of genetic properties of an existing tumor to help determine therapy Tests for Huntington disease mutations Carrier screening for disorders, such as cystic fibrosis, sickle cell anemia, spinal muscular atrophy, and the fragile X syndrome

40. NOT Genetic Information: Information about: Sex or age Routine tests such as complete blood counts (CBC, or blood panel), cholesterol tests, and liver-function tests Analysis, including DNA analysis, of infectious agents such as bacteria, viruses, and fungi, such as HIV.

41. How should the IRB review …. Consider the following 111 findings particularly: Risks Consent Process Privacy and Confidentiality Genetic Research

42. Genetic Research and the 111 findings Risks to Subjects are Minimized Consider non physical risks including psychosocial risks. Examples of minimizing risks: de-identification/anonymous samples or results; not disclosing results to subject or their representatives; limiting the number of staff who have access to identifiable results; not placing identifiable records such as signed consent documents or results in the medical record; obtaining a certificate of confidentiality for identifiable results; avoiding storage of specimens for future testing. Information should be included if genetic counseling will be necessary and plan included on how this process is to be completed.

43. Genetic Research and the 111 findings Reasonable Risk/Benefit Ratio Reasonable Risk/Benefit Ratio Possible Benefits Possible Benefits Subjects may be able to find ways to prevent the disease Subjects may be able to find ways to prevent the disease Generalizable knowledge Generalizable knowledge Possible Risks Possible Risks Risks such as stigmatization, loss of insurance, employment etc.. Risks such as stigmatization, loss of insurance, employment etc.. Learning about an ominous mutation prior to disease symptoms. Learning about an ominous mutation prior to disease symptoms. Mutations can be carried through subsequent generations, affecting as yet unborn descendants; and potential illness can be predicted even for family members, un-enrolled and unaffiliated with the research protocol. Mutations can be carried through subsequent generations, affecting as yet unborn descendants; and potential illness can be predicted even for family members, un-enrolled and unaffiliated with the research protocol. Un-validated results of genetic experiments can still cause actual psycho-social hardship even leading to financial loss. Un-validated results of genetic experiments can still cause actual psycho-social hardship even leading to financial loss. A subject may eventually suffer a serious loss of abilities related to his/her career/every day life; A subject may eventually suffer a serious loss of abilities related to his/her career/every day life; incur higher then usual health care costs; incur higher then usual health care costs; statistically lower life expectancy; or, statistically lower life expectancy; or, ability to procreate and perform socially may become impaired. ability to procreate and perform socially may become impaired.

44. Informed Consent will be sought from each subject Consent document Consent document NY State has particular requirements. Language is currently part of NYU SoM standard templates. NY State has particular requirements. Language is currently part of NYU SoM standard templates. Consent process must be Consent process must be described clearly. described clearly.

45. Protecting Privacy and maintaining Confidentiality Description of all staff who may access identifiable Description of all staff who may access identifiable subject data. Will results be provided to subjects or others. Will results be provided to subjects or others. What are the implications to others besides the subjects including relatives of the participant and the group the subject may be identified with such as racial and/or ethnic. What are the implications to others besides the subjects including relatives of the participant and the group the subject may be identified with such as racial and/or ethnic. Certificate of Confidentiality should be requested when: socially sensitive conditions or traits are studied; tests could have adverse consequences for the participant’s financial standing, insurability, or employability should the results be disclosed outside the research team. Certificate of Confidentiality should be requested when: socially sensitive conditions or traits are studied; tests could have adverse consequences for the participant’s financial standing, insurability, or employability should the results be disclosed outside the research team. De-identification of samples and data before the genetic testing or soon after can minimize risk to subjects and help protect confidentiality. De-identification of samples and data before the genetic testing or soon after can minimize risk to subjects and help protect confidentiality.

46. Genetic Research Useful questions to consider:  Will test results be given?  Will disease risk be quantified, including the limits on certainty of the testing?  Will a change in a family relationship be disclosed, such as mistaken paternity?  Does the subject or family member have the option not to know the results? How will this decision be recorded?  Could other clinically relevant information be uncovered by the study? How will disclosure of this added information occur?  Do any practical limitations exist on the subject's right to withdraw from the research, withdraw data, and/or withdraw DNA?  Is the subject permitted to participate in the study while refusing to have genetic testing (such as in a treatment study with a genetic testing component)?

47. Genetic Research Virginia Commonwealth University (2000) Virginia Commonwealth University (2000) Study involving twins, survey on the similar genetic structures. Study involving twins, survey on the similar genetic structures. Survey intercepted by the parent of twins who agreed to participate - Survey included question regarding parents and other relatives delving into the family tree Survey intercepted by the parent of twins who agreed to participate - Survey included question regarding parents and other relatives delving into the family tree Father complained to the federal authorities Father complained to the federal authorities Research into the genetics of health and psychology climbs through a subject's family tree and across its branches to living family members, the situation adds another ethical wrinkle for scientists trying to ensure privacy of information. Research into the genetics of health and psychology climbs through a subject's family tree and across its branches to living family members, the situation adds another ethical wrinkle for scientists trying to ensure privacy of information. As private citizens question the intrusiveness of research studies into lives beyond that of the person scribbling a signature on an informed consent form, IRBs at universities and medical centers may be forced to reevaluate how they secure informed consent. As private citizens question the intrusiveness of research studies into lives beyond that of the person scribbling a signature on an informed consent form, IRBs at universities and medical centers may be forced to reevaluate how they secure informed consent.

48. Genetic Information Nondiscrimination Act (GINA) 2008 GINA is a Federal law that prohibits discrimination in health coverage and employment based on genetic information. GINA, together with already existing nondiscrimination provisions of the HIPAA, generally prohibits health insurers or health plan administrators from requesting or requiring genetic information of an individual or an individual's family members, or using such information for decisions regarding coverage, rates, or preexisting conditions. GINA also prohibits employers from using genetic information for hiring, firing, or promotion decisions, and for any decisions regarding terms of employment. The law take effect between May 22, 2009, and May 21, 2010, and those relating to employment (Title II) will take effect on November 21, 2009.(1)(1)

49. What Does GINA Do? For Health Insurers* Prohibits group and individual health insurers from using a person’s genetic information in setting eligibility or premium or contribution amounts. Prohibits health insurers from requesting or requiring that a person undergo a genetic test. *Includes Medigap, but not Life, LTC, Disability

50. What Does GINA Do? For Employers Prohibits employers from using a person’s genetic information in decisions such as hiring, firing, job assignments, and promotions. Prohibits employers from requesting, requiring, or purchasing genetic information about an individual employee or family member.

51. GINA and Research Act includes a “research exception” Allows health insurers or group health plans engaged in research to REQUEST, NOT REQUIRE, an individual to undergo a genetic test. Allows health insurers or group health plans engaged in research to REQUEST, NOT REQUIRE, an individual to undergo a genetic test. IRBs should consider the provisions of GINA when assessing whether genetic research satisfies the criteria required for IRB approval of research: IRBs should consider the provisions of GINA when assessing whether genetic research satisfies the criteria required for IRB approval of research: Test is voluntary and CANNOT be required. This information MUST be clear in the plan and consent information Test is voluntary and CANNOT be required. This information MUST be clear in the plan and consent information Research must comply to all elements of 45 CFR 46.111, equivalent federal regulations and any applicable state or local laws for the protection of human research subjects, Research must comply to all elements of 45 CFR 46.111, equivalent federal regulations and any applicable state or local laws for the protection of human research subjects, risks are minimized and reasonable in relation to anticipated benefits risks are minimized and reasonable in relation to anticipated benefits there are adequate provisions in place to protect the privacy of subjects and maintain the confidentiality of their data. there are adequate provisions in place to protect the privacy of subjects and maintain the confidentiality of their data.

52. GINA and Informed Consent OHRP recommends that for genetic research undergoing initial or continuing review reviews, IRBs consider whether consent processes and documents should include language regarding the protections provided by GINA especially risks and confidentiality protections.

54. What are Data and Tissue Repositories Data and Tissue Repositories are… Databases, registries (data banks), and repositories (tissue banks) all involve the collection and storage of information and/or biological specimens over time. Databases, registries (data banks), and repositories (tissue banks) all involve the collection and storage of information and/or biological specimens over time. Some are created and maintained primarily for diagnostic or clinical purposes. Others are created specifically for research. Many serve more than one purpose. Some are created and maintained primarily for diagnostic or clinical purposes. Others are created specifically for research. Many serve more than one purpose.

55. All Data and Tissue Repositories used for research purposes Database created for Research or being used for research Registry Repositories What should the IRB review….

56. Database A database is collection of information elements (i.e., data) arranged for ease and speed of search and retrieval. Most databases are now maintained electronically, but the term can also be applied to paper record systems. Examples of databases include the following: A set of observations (i.e., data) resulting from a research study An electronic file of a medical provider’s patients A collection of diagnosis, treatment, and follow-up information for a hospital’s oncology patients A file of outcomes information compiled for quality assurance activities A list of potential research subjects

57. A registry or “data bank” is a collection of information elements or databases whose organizers; receive information from multiple sources, maintain the information over time, control access to and use of the information by multiple individuals and/or for multiple purposes, which may evolve over time A registry or “data bank” is a collection of information elements or databases whose organizers; receive information from multiple sources, maintain the information over time, control access to and use of the information by multiple individuals and/or for multiple purposes, which may evolve over time Registries often contain codes that link information and specimens to their donor’s identify. Examples of a few well- known registries and data banks include: Registries often contain codes that link information and specimens to their donor’s identify. Examples of a few well- known registries and data banks include: Centers for Disease Control & Prevention (CDC) State Cancer Registries Centers for Disease Control & Prevention (CDC) State Cancer Registries Familial Gastrointestinal Cancer Registry Familial Gastrointestinal Cancer Registry National Registry of Myocardial Infarction (NRMI) National Registry of Myocardial Infarction (NRMI) National Registry of Veterans with Amyotrophic Lateral Sclerosis National Registry of Veterans with Amyotrophic Lateral Sclerosis Registry

58. A repository or “tissue bank” is a collection of biological specimens whose organizers, r eceive specimens from multiple sources, maintain the specimens over time, control access to and use of specimens by multiple individuals and/or for multiple purposes, which may evolve over time Repository: A repository or “tissue bank” is a collection of biological specimens whose organizers, r eceive specimens from multiple sources, maintain the specimens over time, control access to and use of specimens by multiple individuals and/or for multiple purposes, which may evolve over time Repositories usually include demographic and/or medical information about the individuals from whom the specimens were obtained. Repositories usually include demographic and/or medical information about the individuals from whom the specimens were obtained. Repositories often maintain codes that link the information and specimens to their donor’s identify. Examples of a few well-known repositories include: Repositories often maintain codes that link the information and specimens to their donor’s identify. Examples of a few well-known repositories include: The National Human Radiobiology Tissue Repository The National Human Radiobiology Tissue Repository The National Institute of General Medical Sciences (NIGMS) Human Genetic Cell Repository The National Institute of General Medical Sciences (NIGMS) Human Genetic Cell Repository The National Institute on Aging Cell Repository The National Institute on Aging Cell Repository Repository

59. For DNA banking studies, several questions need to be addressed, including: will DNA be stored or shared? If shared, will the subject's identity be known by the new recipient investigator? will DNA be stored or shared? If shared, will the subject's identity be known by the new recipient investigator? will the subject be contacted in the future by the investigator to obtain updated clinical information? will the subject be contacted in the future by the investigator to obtain updated clinical information? how can the subject opt out of any distribution or subsequent use of his/her genetic material? how can the subject opt out of any distribution or subsequent use of his/her genetic material? Data and Tissue Repositories

60.   Two possible submission types   The project establishes the data or tissue repository - would typically receive expedited review   A full board projects includes the collection of data and/or specimens for future use. How should the IRB review Data and Tissue Repositories

61. How should the IRB review Data and Tissue Repositories The IRB should: Review the protocol to determine what will be collected, how will it be stored, who will store it, for how long will it be stored etc.. Evaluate the Informed Consent are subjects provided with information regarding the purpose, description, risks, alternatives etc… for the future use of their data and/or specimens in the main consent?

62. Informed Consent In this study we would like to use some of the tissue we collect for future research. Check below if you agree to allow us to use your tissue.

63. What is missing How long will the tissue be kept? Where will the tissue be kept? Who will have access to the tissue? Will identifiers be kept? Can the subject withdraw the tissue if they change their mind? What will the tissue be used for? Will the subject know when the tissue is being used and will they be able to consent to that use?

64. Capacity to Consent Policy effective March 2009

65. What has changed in our capacity to consent policy? In research involving subjects who lack capacity to consent NYU SoM IRB now allows a Health Care Proxy to consent on behalf of the subject The Health Care Proxy form does not state the patient does not want to participate in research. In the HC proxy form either the patient remains silent with regards to research or has positively affirmed their desire to participate in research.

66. What has NOT Changed… A court-appointed legally authorized representative/guardian; A court-appointed legally authorized representative/guardian; For an investigator to obtain surrogate consent utilizing a health care proxy, the IRB must determine that the research provides potential therapeutic benefit to the subject. For an investigator to obtain surrogate consent utilizing a health care proxy, the IRB must determine that the research provides potential therapeutic benefit to the subject. For human subjects research conducted in other states, requests for the use of surrogate consent will be considered by the IRB in accordance with local state law. For human subjects research conducted in other states, requests for the use of surrogate consent will be considered by the IRB in accordance with local state law.

67. The NYU SOM IRB Policy Research involving persons with impaired decision-making capability may only be approved when the following conditions apply: Research involving persons with impaired decision-making capability may only be approved when the following conditions apply: Only incompetent persons or persons with impaired decision making capacity are suitable as research subjects. Only incompetent persons or persons with impaired decision making capacity are suitable as research subjects. There is a compelling reason to include incompetent individuals or persons with impaired decision-making capacity as subjects. Subjects should not be enrolled because they are readily available. There is a compelling reason to include incompetent individuals or persons with impaired decision-making capacity as subjects. Subjects should not be enrolled because they are readily available. The proposed research entails no significant risks, tangible or intangible. The proposed research entails no significant risks, tangible or intangible.

68. The NYU SOM IRB Policy If the research presents some probability of harm, the following evidence must be included: If the research presents some probability of harm, the following evidence must be included: A greater probability of direct benefit to the participant. A greater probability of direct benefit to the participant. Incompetent people or persons with impaired decision-making capacity are not to be subjects of research that imposes a risk of injury, unless that research is intended to benefit that subject and the probability of benefit is greater than the probability of harm. Incompetent people or persons with impaired decision-making capacity are not to be subjects of research that imposes a risk of injury, unless that research is intended to benefit that subject and the probability of benefit is greater than the probability of harm.

69. Research in NYS and outside of NYS For human subjects research conducted in New York State, NYU SoM’s policy for surrogate consent and its limits must be applied to the research For human subjects research conducted in New York State, NYU SoM’s policy for surrogate consent and its limits must be applied to the research For human subjects research conducted in other states, requests for the use of surrogate consent will be considered by the IRB in accordance with local state law. For human subjects research conducted in other states, requests for the use of surrogate consent will be considered by the IRB in accordance with local state law.

70. Additional Concerns… IRB Approval need to obtain consent from a representative of an adult subject rather than directly from the subject (i.e., surrogate consent) IRB Approval need to obtain consent from a representative of an adult subject rather than directly from the subject (i.e., surrogate consent) A subject previously determined to lack capacity to consent regains capacity during the study must be consented for the remaining part of the study. A subject previously determined to lack capacity to consent regains capacity during the study must be consented for the remaining part of the study. The consent process must disclose all research procedures performed to date and allow the individual an opportunity to continue in or withdraw from the study. The consent process must disclose all research procedures performed to date and allow the individual an opportunity to continue in or withdraw from the study. The subject must sign the IRB-approved consent document and the research record should document what research procedures were already performed or remain to be performed. The subject must sign the IRB-approved consent document and the research record should document what research procedures were already performed or remain to be performed.

71. What you need to know …. IRB must Approve any use of surrogate consent prospectively during review of the protocol or modification of the protocol. Approve any use of surrogate consent prospectively during review of the protocol or modification of the protocol. Submission must include details of how the investigator will verify the authority of the individual to serve as the legally authorized representative designated to provide surrogate consent. Submission must include details of how the investigator will verify the authority of the individual to serve as the legally authorized representative designated to provide surrogate consent. Require investigators to conduct a competency assessment whenever there is a possibility of either impaired mental status or decision-making capacity in prospective subjects. Further, consultation with a psychiatrist or licensed psychologist must be obtained when the determination that the prospective research subject lacks decision- making capacity is based on a diagnosis of mental illness. Require investigators to conduct a competency assessment whenever there is a possibility of either impaired mental status or decision-making capacity in prospective subjects. Further, consultation with a psychiatrist or licensed psychologist must be obtained when the determination that the prospective research subject lacks decision- making capacity is based on a diagnosis of mental illness. If feasible, the investigator must explain the proposed research to the prospective research subject even when the surrogate gives consent. Under no circumstances may a subject be forced or coerced to participate in a research study. If feasible, the investigator must explain the proposed research to the prospective research subject even when the surrogate gives consent. Under no circumstances may a subject be forced or coerced to participate in a research study.

72. Consent Process

73. The Consent Process Informed consent is not a single event or just a form to be signed -- rather, it is an educational process that takes place between the investigator and the prospective subject. The basic elements of the consent process include: full disclosure of the nature of the research and the subject's participation, adequate comprehension on the part of the potential subjects, and the subject's voluntary choice to participate.

74. Regulations require: Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by 45 CFR 46.116 or 21 CFR 50. IRB findings: If the research plan doesn’t tell how Informed Consent will be sought, can the IRB make this finding? Criteria for IRB approval of research

75. What may happen if … TAMPA - A lawsuit accusing USF doctors of experimenting on pregnant women without their consent is settled for $3.8 million…. The experiment wasn't considered risky and no adverse effects were documented, plaintiffs in the suit agree. However, the failure to inform … pregnant women of various experiments conducted between 1986 and 1990 has cost Tampa General Hospital, USF and the state $3.8 million. Tampa Tribune 3/2000

76. Informed Consent Process Sample Protocol Language Each investigator will: Ensure that each patient is given full and adequate oral and written information about the nature, purpose, possible risk and benefit of the study. Ensure that each patient is given full and adequate oral and written information about the nature, purpose, possible risk and benefit of the study. Ensure that the patients are notified that they are free to discontinue from the study at any time Ensure that the patients are notified that they are free to discontinue from the study at any time Ensure that the patients are given the opportunity to ask questions and are allowed time to consider the information provided. Ensure that the patients are given the opportunity to ask questions and are allowed time to consider the information provided. Obtain and document each patient’s signed and dated informed consent before conducting any procedure specifically for the study. Obtain and document each patient’s signed and dated informed consent before conducting any procedure specifically for the study. Ensure that the original, signed Informed Consent Form is stored in a location where it may be immediately retrievable and available. Ensure that the original, signed Informed Consent Form is stored in a location where it may be immediately retrievable and available.

77. Informed Consent Process Sample Protocol Language A properly executed, written, informed consent, in compliance with the Declaration of Helsinki, ICH GCP, US Code of Federal Regulations (CFR) for Protection of Human Subjects (21 CFR 50.25[a,b], CFR 50.27, and CFR Part 56, Subpart A), and local regulations, will be obtained from each patient prior to entering the patient into the trial. The investigator will prepare the informed consent form (ICF) and provide the documents to Sponsor for approval prior to submission to the IRB/IEC. Sponsor and the IRB/IEC must approve the documents before they are implemented. The investigator will provide copies of the signed ICF to each patient and caregiver (or the patient’s legal representative) and will maintain copies in the patient’s record file. The investigator will obtain informed consent from subject and will discuss the purpose of the research, a description of procedures, the risks and any benefits, alternatives to participation, any costs, voluntary participation and a subject’s right to withdraw.

78. Informed Consent Basic Elements Research Purpose/Duration Procedures Experimental Risks Benefits Alternatives Confidentiality Compensation for Injury Whom to Contact Right to Refuse or Withdraw 46.116(a)

79. Informed Consent Additional Elements Currently Unforeseeable Risks Termination of Participation Additional Costs to Subjects Consequence of Withdrawal Informing of New Findings Number of Subjects 46.116(b) 46.116(b)

80. Checklist for Consent Process Investigator describes how it is done- Initial meeting in person, over the phone, by mail or email? given time to digest information/ask questions Assessment of understanding Is the process coercive Continued Consent Process Does the protocol include provisions for continued IC process – If not, is that OK? Investigator includes: Who, What, Where and When Are qualified personnel conducting the consent process? What will be discussed with subject Physical Environment Timing

81. New protocol considerations: New protocol considerations: Are procedures for an ongoing process described? Are procedures for an ongoing process described? When and by whom will consent be obtained? When and by whom will consent be obtained? How will competency be addressed? How will competency be addressed? Is surrogate consent proposed, and if so, is it acceptable? Is surrogate consent proposed, and if so, is it acceptable? Renewals: Renewals: Has consent been obtained from enrolled subjects? Has consent been obtained from enrolled subjects? Is the consent process adequate or are changes required? Is the consent process adequate or are changes required? Is there new information that should be, but has not yet been, conveyed to enrolled subjects? Is there new information that should be, but has not yet been, conveyed to enrolled subjects? Consent Process

82. One last thing… …Remember the 111 findings – these are the basis of what we do and why we do it Risk to Subjects are minimized Risk/Benefit Ratio is favorable Subject Selection is equitable Informed Consent is obtained and documented Privacy is protected Confidentiality is maintained Vulnerable Subjects are protected

83. Thank You