The New Crisis in Human Subject Protection: Is Accreditation the Answer?

1. The New Crisis in Human Subject Protection: Is Accreditation the Answer? Steven Smith California Western School of Law April 15, 2005

2. Summary • The use of human subjects in medical and social science research is critical to the advancement of medicine. • Continued support for this research is, however, threatened by the disclosure of research misconduct. • The medical and higher education communities should take steps to maintain confidence in human studies, and to some extent are doing so.

3. The extent of the use of humans in research is not known, but it is estimated that in the U.S.: • More than 20 million people participate in human studies annually. • More than $60 billion is spent on biomedical research annually. • Perhaps 60,000 researchers conduct clinical trials in the U.S. • The number of clinical trials in the US may exceed 100,000 annually. • There are 3 to 5,000 IRBs (I have no faith in most of these data)

4. Public Confidence • 83% of adults believe it is essential or very important to test new drugs or treatments on humans in clinical trials before they are approved for general use • Only 24% are very confident that patients in clinical trials are treated as patients and not “guinea pigs” • 25% are very confident they are “told honestly of the risks” • Only 20% are very confident that doctors and hospitals do not recruit them “so they can make more money” • Minority respondents were generally less confident in the legitimacy and safety of participating in human studies • From Harris Interactive Survey, 2002

5. “Human experimentation has existed throughout human history” “God created man”

6. “So God caused a deep sleep to fall upon the man and while he slept took one of his ribs and closed up its lace with flesh [and] the rib he made into a woman.”

7. Traditional Control of Medical Experiments on Humans Tort Liability Criminal Liability License Discipline

8. Human Subject Protection Crisis I

9. "Permissible Medical Experiments."Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10. Nuremberg October 1946 - April 1949, Washington. U.S. Government Printing Office, vol. 2., pp. 181-182. 1. The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion, and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person which may possibly come from his participation in the experiment. The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.

10. 2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature. 3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment. 4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury. 5. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects. 6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.

11. 7. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury disability or death. 8. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment. 9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible. 10. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgment required by him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.

12. WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI   Ethical Principles for Medical Research Involving Human Subjects Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the29th WMA General Assembly, Tokyo, Japan, October 197535th WMA General Assembly, Venice, Italy, October 198341st WMA General Assembly, Hong Kong, September 198948th WMA General Assembly, Somerset West, Republic of South Africa, October 1996and the 52nd WMA General Assembly, Edinburgh, Scotland, October 2000 Note of Clarification on Paragraph 29 added by the WMA General Assembly, Washington 2002Note of Clarification on Paragraph 30 added by the WMA General Assembly, Tokyo 2004

13. INTRODUCTION The World Medical Association has developed the Declaration of Helsinki as a statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects. Medical research involving human subjects includes research on identifiable human material or identifiable data. It is the duty of the physician to promote and safeguard the health of the people. The physician's knowledge and conscience are dedicated to the fulfillment of this duty. The Declaration of Geneva of the World Medical Association binds the physician with the words, "The health of my patient will be my first consideration," and the International Code of Medical Ethics declares that, "A physician shall act only in the patient's interest when providing medical care which might have the effect of weakening the physical and mental condition of the patient." Medical progress is based on research which ultimately must rest in part on experimentation involving human subjects. In medical research on human subjects, considerations related to the well-being of the human subject should take precedence over the interests of science and society. The primary purpose of medical research involving human subjects is to improve prophylactic, diagnostic and therapeutic procedures and the understanding of the aetiology and pathogenesis of disease. Even the best proven prophylactic, diagnostic, and therapeutic methods must continuously be challenged through research for their effectiveness, efficiency, accessibility and quality. In current medical practice and in medical research, most prophylactic, diagnostic and therapeutic procedures involve risks and burdens. Medical research is subject to ethical standards that promote respect for all human beings and protect their health and rights. Some research populations are vulnerable and need special protection. The particular needs of the economically and medically disadvantaged must be recognized. Special attention is also required for those who cannot give or refuse consent for themselves, for those who may be subject to giving consent under duress, for those who will not benefit personally from the research and for those for whom the research is combined with care. Research Investigators should be aware of the ethical, legal and regulatory requirements for research on human subjects in their own countries as well as applicable international requirements. No national ethical, legal or regulatory requirement should be allowed to reduce or eliminate any of the protections for human subjects set forth in this Declaration.

14. BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH It is the duty of the physician in medical research to protect the life, health, privacy, and dignity of the human subject. Medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and on adequate laboratory and, where appropriate, animal experimentation. Appropriate caution must be exercised in the conduct of research which may affect the environment, and the welfare of animals used for research must be respected. The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol. This protocol should be submitted for consideration, comment, guidance, and where appropriate, approval to a specially appointed ethical review committee, which must be independent of the investigator, the sponsor or any other kind of undue influence. This independent committee should be in conformity with the laws and regulations of the country in which the research experiment is performed. The committee has the right to monitor ongoing trials. The researcher has the obligation to provide monitoring information to the committee, especially any serious adverse events. The researcher should also submit to the committee, for review, information regarding funding, sponsors, institutional affiliations, other potential conflicts of interest and incentives for subjects. The research protocol should always contain a statement of the ethical considerations involved and should indicate that there is compliance with the principles enunciated in this Declaration. Medical research involving human subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent medical person. The responsibility for the human subject must always rest with a medically qualified person and never rest on the subject of the research, even though the subject has given consent. Every medical research project involving human subjects should be preceded by careful assessment of predictable risks and burdens in comparison with foreseeable benefits to the subject or to others. This does not preclude the participation of healthy volunteers in medical research. The design of all studies should be publicly available. Physicians should abstain from engaging in research projects involving human subjects unless they are confident that the risks involved have been adequately assessed and can be satisfactorily managed. Physicians should cease any investigation if the risks are found to outweigh the potential benefits or if there is conclusive proof of positive and beneficial results.

15. Medical research involving human subjects should only be conducted if the importance of the objective outweighs the inherent risks and burdens to the subject. This is especially important when the human subjects are healthy volunteers. Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the results of the research. The subjects must be volunteers and informed participants in the research project. The right of research subjects to safeguard their integrity must always be respected. Every precaution should be taken to respect the privacy of the subject, the confidentiality of the patient's information and to minimize the impact of the study on the subject's physical and mental integrity and on the personality of the subject. In any research on human beings, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail. The subject should be informed of the right to abstain from participation in the study or to withdraw consent to participate at any time without reprisal. After ensuring that the subject has understood the information, the physician should then obtain the subject's freely-given informed consent, preferably in writing. If the consent cannot be obtained in writing, the non-written consent must be formally documented and witnessed. When obtaining informed consent for the research project the physician should be particularly cautious if the subject is in a dependent relationship with the physician or may consent under duress. In that case the informed consent should be obtained by a well-informed physician who is not engaged in the investigation and who is completely independent of this relationship. For a research subject who is legally incompetent, physically or mentally incapable of giving consent or is a legally incompetent minor, the investigator must obtain informed consent from the legally authorized representative in accordance with applicable law. These groups should not be included in research unless the research is necessary to promote the health of the population represented and this research cannot instead be performed on legally competent persons. When a subject deemed legally incompetent, such as a minor child, is able to give assent to decisions about participation in research, the investigator must obtain that assent in addition to the consent of the legally authorized representative. Research on individuals from whom it is not possible to obtain consent, including proxy or advance consent, should be done only if the physical/mental condition that prevents obtaining informed consent is a necessary characteristic of the research population. The specific reasons for involving research subjects with a condition that renders them unable to give informed consent should be stated in the experimental protocol for consideration and approval of the review committee. The protocol should state that consent to remain in the research should be obtained as soon as possible from the individual or a legally authorized surrogate. Both authors and publishers have ethical obligations. In publication of the results of research, the investigators are obliged to preserve the accuracy of the results. Negative as well as positive results should be published or otherwise publicly available. Sources of funding, institutional affiliations and any possible conflicts of interest should be declared in the publication. Reports of experimentation not in accordance with the principles laid down in this Declaration should not be accepted for publication.

16. ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH MEDICAL CARE The physician may combine medical research with medical care, only to the extent that the research is justified by its potential prophylactic, diagnostic or therapeutic value. When medical research is combined with medical care, additional standards apply to protect the patients who are research subjects. The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists. At the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study. The physician should fully inform the patient which aspects of the care are related to the research. The refusal of a patient to participate in a study must never interfere with the patient-physician relationship. In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic methods do not exist or have been ineffective, the physician, with informed consent from the patient, must be free to use unproven or new prophylactic, diagnostic and therapeutic measures, if in the physician's judgement it offers hope of saving life, re-establishing health or alleviating suffering. Where possible, these measures should be made the object of research, designed to evaluate their safety and efficacy. In all cases, new information should be recorded and, where appropriate, published. The other relevant guidelines of this Declaration should be followed

17. Crisis II Events • 1962-- Fetal abnormalities from Thalidomide • 1964-- Brooklyn Jewish Chronic Disease Hospital Experiments • 1966-- Beecher article in NEJM • 1971-- Willowbrook School for the Mentally Retarded Experiments • 1972-- Tuskegee Syphilis Study

18. Legal Response • National Research Act 1972 • Belmont Report • HEW/FDA regulations establishing IRBs

19. Department of Health, Education, and WelfareOffice of the SecretaryPROTECTION OF HUMAN SUBJECTSBELMONT REPORT:ETHICAL PRINCIPLES AND GUIDELINESFOR THE PROTECTION OFHUMAN SUBJECTS OF RESEARCHReport of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research Table of Contents Summary Members of the Commission The Belmont Report: An Introduction • Boundaries Between Practice and Research • Basic Ethical Principles • Respect for Persons • Beneficence • Justice • Applications • Informed Consent • Assessment of Risk and Benefits • Selection of Subjects

20. The Age of the IRB • Decentralized decision-making • Community-based decisions reflecting the values of the community • Subject of Federal Guidelines, but little federal oversight • The “Common Rule” • The FDA and HHS

21. Roles of the IRB In reviewing proposed research involving human subjects, generally the IRB is to determine: (1) that risks to subjects are minimized through the use of a sound research design; (2) that risks are reasonable in relation to anticipated benefits; (3) that the selection of subjects is equitable; (4) that appropriate informed consent will be sought from each subject; (5) that the informed consent will be appropriately documented; (6) that if appropriate, the research plan will provide for monitoring of data; and (7) that if needed there are adequate provisions to protect subjects' privacy and maintain confidentiality of data.

22. A Third Crisis Develops • 1996--General Accounting Office - heavy workloads, lack of preparedness of IRB, limited resources • 1998--Office of Inspector General, DHHS - IRBs overwhelmed; issued a warning signal • 1999--Jesse Gelsinger died in U. Pa. in gene therapy study • 2000--Suit filed in U. of Oklahoma melanoma vaccine study • 2001--Ellen Roche, a healthy volunteer, died in an asthma study at Hopkins

23. Potential Legal Controls • Civil Liability • Criminal Liability • License Discipline • Direct Regulation • Indirect Regulation (e.g., FDA) • Federal Funding

24. Suspensions of Federally Supported Research • March 1999 Greater Los Angeles Health Care System, West Los Angeles • May 1999 Duke University Medical Center • August 1999 University of Illinois, Chicago • January 2000 Virginia Commonwealth • June 2000 University of Oklahoma Health Sciences Center • July 2001 Johns Hopkins Medical

25. FDA warning letters to IRBs 52 Warning Letters were issued to IRBs from Jan 1997 to July 2004 Ref: Bramstedt, A and Kassimatis, K. Clin Invest Med 27:6 (Dec 2004): 316-323

26. Liability • Gelsinger v. Trustees of the Univ. of Pennsylvania • Robertson v. McGee • Wright v. Hutchinson • Berman v. Hutchinson • Grimes v. Kennedy Krieger Inst. • Heinrich v. Sweet • Sexton v. United States • Whitlock v. Duke Univ. • Doe v. Ill. Masonic Med. Ctr.

27. Problems with the Current Approach to Subject Protection • There are inherent problems with institutional reviews (inconsistency, pressure from local officials) • Some research is not subject to any review (not subject to federal law or avoided illegally) • There is very little federal oversight of the operation of IRBs • There is no continuing, organized national system to address recurring issues and problems • There is an inadequate and excessively technical focus on informed consent

28. Problems with IRBs • Inadequate IRB resources and staffing • Inadequate training of IRB members and staffs • Inadequate review of implementation of IRB limits on approved studies • Inadequate continuing review • Inadequate reporting of adverse events • Increase in numbers and complexity of studies is outpacing IRBs’ ability to keep up

29. Problems Caused By Changing Conditions • Internationalization of research • Multicenter studies are poorly handled • Commercialization of research and conflicts of financial interest complicate matters • Inadequate mechanisms of compensating those injured in studies • Declining public confidence

30. Problems With Error Reduction • IRBs receive very little feedback of any kind • There is little systematic IRB collection of error data on which improvements could be based • There is no national recordkeeping of approved studies and the experience of IRBs • There is limited education of researchers and limited commitment to the highest ethical principles in research

31. Accreditation as a Partial Solution • The goal of accreditation is said to be to protect “the rights and welfare of research participants by fostering and advancing the ethical and professional conduct of persons and organizations that engage in research with human participants.” • In fact, it may be to provide sufficient self-regulation to avoid more difficult outside regulation.

32. Association for the Accreditation of Human Subject Protection Programs Founding Members: • Association of American Medical Colleges • Association of American Universities • Consortium of Social Science Associations • Federation of American Societies for Experimental Biology • National Association of State Universities and Land-Grant Colleges • National Health Council • Public Responsibility in Medicine and Research

33. Accredited Organizations • Baylor College of Medicine • Baylor Research Institute • Catholic Medical Center • Cedars-Sinai Medical Center • Chesapeake Research Review, Inc. • Children’s Hospital Boston • Copernicus Group IRB • Dana Farber/Harvard Cancer Center • East Tennessee State University • Fox Chase Cancer Center • Hunter Holmes McGuire VAMC • Indiana University – Purdue University, Indianapolis (IUPUI) • Iowa Health – Des Moines • Johns Hopkins Medical Institutions • Massachusetts General Hospital and Brigham & Women’s Hospital as part of Partners Healthcare System • Michigan State University

34. Accredited Institutions (2) • New England Institutional Review Board • Newton-Wellesley Hospital • Saint Francis Hospital and Medical Center • The University of Arizona • The University of Iowa • The University of New Mexico Health Sciences Center • The University of South Dakota • University of Arkansas for Medical Sciences • University of California, Irvine • University of California, San Francisco • University of Louisville • University of Maryland, Baltimore • University of Minnesota • University of Pittsburgh • Vanderbilt University • Washington University in St. Louis • Western Institutional Review Board

35. Accreditation standards • Human Research Protection Program • Domain 1: Organization • Domain 2: Research Review Unit (IRB) • Domain 3: Investigator • Domain 4: Sponsored Research • Domain 5: Participant Outreach

36. Benefits of accreditation – For organizations • Improves overall quality of research program through better and more effective processes that are appropriate to volume and nature of research conducted by the organization • Promotes culture of responsible conduct of research • Improves protections for research subjects • Ensures compliance with regulations • Better enrollment in clinical trials

37. Is There Salvation in Accreditation?

38. Where Do We Go From Here?

39. The Domains: Organization • OrganizationThe "Organization" is the entity that assumes responsibility for the Human Research Protection Program and applies for accreditation. The entity may be an academic institution, clinic, hospital, managed care organization, contract research organization, or a corporate entity, such as a pharmaceutical or biotechnology company, or an independent review board. Despite great dissimilarities in how such entities are structured, the Organization domain identifies those elements that must be evident, albeit in various different forms, in an entity that seeks accreditation for its Human Research Protection Program.

40. The Domains: Research Unit • Research Review UnitThe domain of “Research Review Unit” refers to the arrangements that the Organization has made for an independent review of ethical and scientific aspects of each research protocol involving human participants. Such activities are generally carried out by an institutional review board (IRB). Organizations with multiple IRBs might have a general oversight office or an individual with oversight responsibility. In these complex structures the functions and activities are split between the oversight office or individual with such responsibility and the IRBs. In recognition of these complex structures, the term “Research Review Unit” is used to describe the domain rather than IRB. The review and other activities of the IRB are concerned with protecting the rights and welfare of the participants. In the review process, IRBs must ensure that the scientific validity of a research protocol is considered as well as the risks and potential benefits to participants and benefits that might accrue to society. In addition, IRBs are responsible for reviewing research on an ongoing basis, monitoring reports of new information affecting risks and potential benefits, and assuring that the interests of research participants are protected.

41. Domains: Investigator • InvestigatorThe "Investigator" domain includes the various arrangements that the Organization has made for assuring that individuals who plan to conduct research — whether as a principal investigator, co-investigator, or other member of a research team — understand and fulfill their responsibilities. Fundamentally, these responsibilities stem from the fact that an individual conducting research enters into arrangements that may intentionally expose human participants to some degree of risk — whether physical, psychological, economic, legal, or social — for scientific purposes.

42. The Domains: Sponsored Research • Sponsored ResearchThe "Sponsored Research" domain includes the Organization’s arrangements for structuring its relationships with those who fund or initiate research external to the Organization, such as federal agencies, foundations, individual donors, and corporations (e.g., pharmaceutical or biotechnology companies); usually referred to as sponsored research. The Organization seeking accreditation must apply its Human Research Protection Program to all sponsored research and address any special issues that might arise. These issues include, but are not limited to, the ethical conduct of research, dissemination of knowledge gained from research, and availability of health care to injured research participants.

43. The Domains: Participant Outreach • Participant OutreachThe "Participant Outreach" domain refers to the arrangements the Organization has made for understanding the social, psychological, and physical needs and concerns of research participants and their communities. Organizations and investigators who provide education to participants relevant to their participation in the research process should provide them with tools and resources to assume an active, responsible role in research. Participants might provide important feedback to investigators about their experience during the informed consent process and during the research itself, which can be helpful in design of future studies.

44. Accreditation standards:Research Review Unit, including IRBs Accreditation standards:Research Review Unit, including IRBsThe following are AAHRPP accreditation standards related to the research review unit / IRB...STANDARD II-1:The structure and composition of the Research Review Unit are appropriate to the amount and nature of the research reviewed. ELEMENTSII.1.A. The Research Review Unit has and follows written policies and procedures requiring protocols to be reviewed by individuals with appropriate scientific or scholarly expertise. II.1.B. The IRB has a process for obtaining additional expertise when reviewing a specific protocol. II.1.C. The Research Review Unit has and follows written policies and procedures so that IRB members and consultants do not participate in the review of protocols in which they have a conflict of interest, except to provide information requested by the IRB. II.1.D. The IRB has a qualified IRB chair, members, and staff, whose membership and composition are periodically reviewed. The IRB administrator, staff, chair, and members have knowledge, skills, and abilities appropriate to their respective roles. II.1.E. The IRB membership roster includes sufficient information about members to permit appropriate representation at the meeting for each protocol under review. One or more unaffiliated members are represented on the IRB and one or more members can represent the general perspective of participants. II.1.F. The IRB meets regularly and members have sufficient time to review materials prior to meeting.

45. STANDARD II-2:The Research Review Unit systematically evaluates each research study to ensure the protection of participants. • ELEMENTS • II.2.A. The Research Review Unit has and follows written policies and procedures for conducting initial and continuing review, and procedures for handling modifications to research studies. • II.2.B. The Research Review Unit has and follows written policies and procedures to conduct reviews by the expedited procedure. • II.2.C. The Research Review Unit receives and reviews the relevant information to evaluate research studies during initial review. • II.2.D. The Research Review Unit receives and considers relevant information to conduct continuing reviews of research studies and, when appropriate, requests changes. • II.2.E. The Research Review Unit receives and considers the relevant information to evaluate proposed amendments to research studies. • STANDARD II-3: The Research Review Unit maintains documentation of its activities. • ELEMENTS • II.3.A. The Research Review Unit maintains a complete set of materials relevant to review of the research study in each protocol file. • II.3.B. The Research Review Unit retains required records for a period of time sufficient to meet federal, state, and local regulations, sponsor requirements, and organizational policies and procedures. • II.3.C. The IRB documents pertinent discussions and decisions on research studies and activities.

46. . • STANDARD II-4:The Research Review Unit systematically evaluates risks to participants and potential benefits as part of the initial review and ongoing review of research. • ELEMENTS • II.4.A. The Research Review Unit has and follows written policies and procedures for identifying and analyzing potential sources of risk and measures to minimize risk, including physical, psychological, social, legal, or economic risks. The analysis of risk includes a determination that the risks to participants are reasonable in relation to potential benefits to participants and to society. • II.4.B. The Research Review Unit reviews the plan for data and safety monitoring in research protocols, when applicable, and determines that the plan provides adequate protection for participants. • II.4.C. The Research Review Unit has and follows written policies and procedures for determining the risks to vulnerable populations as defined in applicable federal regulations, and specifically for determining the required risk categories in protocols involving children and prisoners. • II.4.D. The Research Review Unit has and follows written policies and procedures for suspending or terminating previously approved research if warranted by findings in the continuing review or monitoring process. • STANDARD II-5:The Research Review Unit systematically evaluates recruitment and participant selection practices. • ELEMENTS • II.5.A. The Research Review Unit has and follows written policies and procedures to evaluate the equitable selection of participants from various populations and sub-populations, when applicable, and considers whether inclusion and exclusion criteria impose fair and equitable burdens and benefits. • II.5.B. The Research Review Unit reviews proposed participant recruitment methods, advertising materials, and participation payment arrangements, and permits them when fair, honest, and appropriate.

47. STANDARD II-6:The Research Review Unit systematically evaluates the protection of privacy interests of research participants and the confidentiality of data in proposed research. • ELEMENTS • II.6.A. The Research Review Unit has written policies and procedures to evaluate the proposed arrangements for protecting the privacy interests of research participants during and after their involvement in the research. • II.6.B. The Research Review Unit has written policies and procedures to evaluate proposed arrangements for protecting the confidentiality of identifiable data, when appropriate, during and after the conclusion of the investigation. • STANDARD II-7:The Research Review Unit has and follows written policies and procedures that require informed consent to be solicited from participants or their legally authorized representatives, and it verifies that this requirement is met. • ELEMENTS • II.7.A. The Research Review Unit evaluates compliance with policies and procedures on seeking informed consent from participants or their legally authorized representatives, and assent, when possible, from participants who cannot give consent. • II.7.B. The Research Review Unit has and follows written policies and procedures requiring that prospective participants whose decision-making capacity is in question be appropriately protected. • II.7.C. The Research Review Unit reviews the content of the consent process, including the consent document, and the process through which informed consent is obtained from each participant, focusing on measures to improve participant understanding and voluntary decision-making. • II.7.D. The Research Review Unit has and follows written policies and procedures requiring that the investigator has and follows a procedure for properly documenting informed consent. • II.7.E. The Research Review Unit has and follows written policies and procedures for approving waiver or alteration of the consent process and the waiver of consent documentation. • II.7.F. The Research Review Unit has and follows written policies and procedures for making exceptions to informed consent requirements in protocols for emergency situations, and appropriately reviews such protocols. • II.7.G. The Research Review Unit has procedures for observation of the informed consent process in ongoing research, when appropriate.

48. STANDARD II-8:The Research Review Unit has procedures for review and oversight of research conducted at multiple sites. • ELEMENTS • II.8.A. The Research Review Unit has and follows policies and procedures for communication among IRBs, when appropriate, for research conducted at multiple sites (e.g., multi-site clinical trials, epidemiology studies, or educational surveys). • II.8.B. The Research Review Unit has and follows policies and procedures for management of information obtained in multi-site research that may be relevant to the protection of research participants, such as reporting of unexpected problems or interim results.