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.

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• 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.

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• 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.

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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

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• 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.

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• 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.

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• 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

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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

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Legal Response

• National Research Act 1972
• Belmont Report
• HEW/FDA regulations establishing IRBs

19
Department of Health, Education, and Welfare
Office of the Secretary PROTECTION OF HUMAN
SUBJECTS BELMONT REPORT ETHICAL PRINCIPLES AND
GUIDELINES FOR THE PROTECTION OF HUMAN SUBJECTS
OF RESEARCH Report 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 276 (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.

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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.
• Childrens 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
  Womens 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.

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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.

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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 Organizations 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.

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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 standardsResearch Review Unit,
including IRBs

• Accreditation standardsResearch Review Unit,
  including IRBsThe following are AAHRPP
  accreditation standards related to the research
  review unit / IRB...STANDARD II-1The 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-2The 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.

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• .
• STANDARD II-4The 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-5The 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.

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• STANDARD II-6The 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-7The 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.

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• STANDARD II-8The 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.

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