THE INSTITUTIONAL REVIEW BOARD AND THE ROLE OF THE HOSPITAL LIBRARIAN

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THE INSTITUTIONAL REVIEW BOARD AND THE ROLE OF
THE HOSPITAL LIBRARIAN

• Dr. David M. Svinarich
• Director, Patient Care Research
• Providence Hospital
• Southfield, Michigan

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WHAT IS AN INSTITUITONAL REVIEW BOARD?The
Institutional Review Board (IRB) is a group of
individuals who

• Examine and regulate all research pertaining to
  humans at a given institution
• Ensure that the proposed research is ethical
• Ensure that the proposed research has some
  practical value (beneficence)
• Ensure that patient confidentiality is maintained
• Ensure the preparation of proper and complete
  informed consents
• Ensure compliance with all federal, state, local
  and institutional regulations and directives.

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WHAT CONSTITUTES A TYPICAL INSTITUTIONAL REVIEW
BOARD?The IRB, by design, consists of a diverse
group of individuals who function independently
from the institution they represent.

• Physicians
• Scientists
• Lay people
• Religious leaders
• Nurses
• Research librarians

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WHAT IS THE ROLE OF THE HOSPITAL LIBRARIAN?

• Hospital librarians are increasingly being asked
  to become involved with the IRB at their
  institutions
• Serving as an IRB advisor
• Serving as a full IRB board member
• Conducting current literature searches for
  investigators
• Serving as an impartial source of information

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Historical Notes The Current Climate
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HOSPITAL LIBRARIANS AND THE JOHNS HOPKINS TRAGEDY

• The death of a healthy volunteer in a clinical
  trial raised many questions about the IRB process
  and the responsibility of the principal
  investigator. This death was attributed at least
  in part to a failure to uncover literature that
  indicated possible adverse effects of the study
  drugs, thereby resulting in inadequate informed
  consent of the participants.
• While few hospital librarians have been directly
  involved in clinical trials to date, your
  research skills are being increasingly relied
  upon to make risk assessments and to evaluate
  drug/therapy effectiveness and safety.

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BackgroundOn May 4, 2001, Ellen Roche (age 24)
was a volunteer for a study on asthma at Johns
Hopkins University. She was given a combination
therapy of hexamethonium and sodium bicarbonate.
Five days after inhalation of these drugs she was
admitted to the Bayview Medical Center in
Baltimore. She developed progressive major organ
failure and died on June 2nd of that year.What
Went Wrong?No one factor can be singled out as
the primary contributor to this tragedy.
However, a series of errors, omissions and lax
practices were uncovered during the
investigation1. Failure to request FDA approval
prior to conducting the trial.2. Altering the
approved study protocol without input or
permission from the Johns
Hopkins IRB.3. Failure to inform the IRB that
the inhalation form of
hexamethonium was experimental use of the
chemical.4. Failure to mention the possible
toxic effects of the substance on the ICF.5. Not
reporting symptoms in a previous test subject,
who recovered uneventfully.
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The Research ProcessThe principal
investigators search strategy indicates that he
performed a standard PubMed search for
potential hexamenthonium toxicity and consulted
standard current edition textbooks of
pharmacology and pulmonary medicine. He also
search the Web using the Google, Yahoo, Looksmart
and GoTo.com, search engines.In contrast,
Hospital Librarians are familiar with and trained
to use wide variety of commercial online
databases, search engines, conference and other
reports, textbooks, CD-ROM databases,scientific
papers, safety reviews, manufacturers material
safety data sheets, abstract and citation
indexes, discussion lists and personal contacts.

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Conclusions

• Ellen Roches death has served to draw attention
  to the flaws in the information gathering process
  and the need for appropriate prospective
  literature searching.
• As part of their responses to the FDA John
  Hopkins has, among other safeguards pledged to
  require
• 1. Supplementing Web-based instruction for
  faculty and staff on use of humans in research
  by presenting at Hopkins the nationally
  acclaimed PRIMIR course IRB 101.
• 2. Prior academic review of research protocols
  before they are submitted to IRBs. This will
  include examination of scientific worth,
  validity of study design and safety.
• 3. Investigators will be required to
  collaborate with a librarian and a pharmacist
  to strengthen literature searches. The goal of
  which is to ensure that appropriate databases
  are searched for potential side effects
• The research at Johns Hopkins failed to uncover
  literature which indicated possible adverse
  effects of the study drug, resulting in
  inadequate informed consent for participants.

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Challenges and points to consider

• Scientists and Physicians are not as well
  acquainted with the breadth of informational
  resources available as librarians are
• Scientists and Physicians will generally use the
  most convenient search engines and databases
  available without regard to breadth or
  appropriateness
• Scientists and Physicians lack expertise, time
  and inclination to perform the type of literature
  search necessary to adequately investigate a
  clinical study
• Scientists and Physicians need to be taught
  appropriate literature search skills but must
  collaborate with and rely upon trained research
  librarians
• Librarians need to adequately convey to
  scientists and physicians the necessity for a
  trained person to conduct literature
  reviews-particularly in human trials.

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An Introduction to Human Research Ethics
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Purpose
This presentation serves as a basic introduction
to the foundations, principles, ethics and
regulations concerning the use of human subjects
in research. The following are the subparts that
will be explored the historical need for ethical
review of human use research, design and function
of the institutional review board (IRB), the
essential nature of informed consent and
responsibilities of IRB systems. While it is not
possible to cover every regulatory and ethical
aspect of human research, I hope that this
opportunity will make participants aware of some
of the general concepts and intricacies involved.
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The scientific research enterprise, like other
human activities, is built on a foundation of
trust..this trust will endure only if the
scientific community devotes itself to
exemplifying and transmitting the values
associated with ethical scientific conduct.
Preface, On Being A Scientist National Academy of
Sciences Fifth Printing, 1999
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Table of Contents

• Historical Notes
• Basic Principles The Nuremberg Code
• The Belmont
  Report
• Regulatory
  Documents
• Informed Consent Process and Critical
  Elements
• IRB Systems
• Education, Training and Certification Needs
• Conclusion IRB Ethics and the Ethos of
  Research

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Historical Notes
The Nazi Holocaust Unit 731 Atrocities of WW
II The Tuskegee Syphilis Study 1932 The
Massachusetts Radiation/Nutrition Studies
1943 The Willowbrook State School Case 1954
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Historical Notes The Ethical Results
In the aftermath of the Nazi holocaust and
continuing over time with other examples of
difficulties in medical and research
experimentation, the world community has
articulated consistently that the protection of
human subjects from research risks can never be
compromised. Protecting human subjects from
research risks is not just a matter of
fulfilling legal requirements or completing
simple clerical tasks. It is an ethical and
regulatory responsibility for all investigators
and all research programs enrolling human
subjects in research.
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Historical Notes (contd)
In the years following World War II, the swift
expanse of new scientific technologies and a
heightened understanding of the human person and
human rights coupled together to give new energy
to the protection of human subjects from research
risks. Scientific advancement, broad ethical
concerns and the revelation of new challenges in
human subjects research resulted in a need for
strict standards for human subject protections.
The resulting regulatory requirements were
based upon specific central principles. These
principles were articulated in a variety of ways
and, over time, gave rise to our present day
federal codes and other requirements documents.
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Historical Notes (contd)
Two specific documents articulate well the
critical principles for human subjects
protections
The Nuremberg Code The Belmont Report
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Basic Principles
21
Basic Principles The Nuremberg Code
The Nuremberg Code was developed as a direct
result of the Nazi medical experiment atrocities
committed during World War II. The Nazi medical
atrocities were revealed at the now famous
Nuremberg Trials. The Code makes clear that the
welfare and rights of human subjects must be
protected, that the research conducted must be
sound and beneficial, and that the freedom of
human subjects to participate or not is
inviolable.
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Basic Principles The Nuremberg Code
...The voluntary consent of the human subject is
absolutely essential. ...The experiment should
yield fruitful results for the good of society,
unprocurable by other methods or means of study,
and not random and unnecessary in nature. ...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. ...The experiment should be so
conducted as to avoid all unnecessary physical
and mental suffering and injury.
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Basic Principles The Nuremberg Code
...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. ...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. ...Proper preparations should be
made and adequate facilities provided to protect
the experimental subject against even remote
possibilities of injury, disability, or
death. ...The experiment should be conducted
only by scientifically qualified persons.
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Basic Principles The Nuremberg Code
...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. ...During the course of the
experiment the human subject should be at
liberty to bring the experiment to an end if he
sic has reached the physical or mental state
where continuation of the experiment seemed to
him to be impossible. ...During the course of
the experiment, the scientist in charge must be
prepared to terminate the experiment at any
stage if he sic has probable cause to believe,
in the exercise of the good faith, superior
skill and careful judgment required of him that a
continuation of the experiment is likely to
result in injury, disability, or death of the
experiment subject.
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Basic Principles The Belmont Report
In April of 1979, the National Commission for the
Protection of Human Subjects of Biomedical and
Behavioral Research issued The Belmont Report.
The work of the Commission was made necessary due
to a long history of various questions,
concerns, difficulties and problems that arose in
medical experimentation and other forms of
research efforts involving the enrollment
of human subjects. This long history prompted the
issuance of guiding principles for the
protection of human subjects. The Belmont Report
articulated the three basic principles of human
subjects protections that have become the
groundwork for all subsequent regulations and
guidelines.
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Basic Principles The Belmont Report
The three basic principles of the Belmont
Report for the protection of human subjects are
RESPECT BENEFICENCE JUSTICE
These principles are described briefly as follows.
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Basic Principles The Belmont Report
RESPECT FOR PERSONS ...The freedom and capacity
of subjects must be protected. ...Each subject
is an autonomous agent. Special measures must
be taken to protect the rights and welfare of
persons with diminished autonomy. ...Informed
consent is central to protecting the autonomy of
human subjects.
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Basic Principles The Belmont Report
BENEFICENCE ...Researchers have the obligation
to secure the well-being of subjects. ...All
efforts must be based firmly upon the principle
Do No
Harm. ...Possible benefits must be
maximized. ...Possible harms must be minimized.
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Basic Principles The Belmont Report
JUSTICE ...Researchers must ask Who should
receive the benefits of research and bear its
burdens? ...There must be fairness in the
distribution of the risks and benefits of the
research. ...Each person must equally share in
the risks/benefits distribution according to
individual need, individual effort, societal
contribution, and merit.
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Basic Principles Regulatory Documents
After the issuance of the Nuremberg Code and the
Belmont Report, the evolving challenges in
research and the increasing appreciation of human
subject protections led to a variety
of regulatory documents and requirements.
Beginning with the US Code of Federal
Regulations, these requirements are interpreted
and passed down for implementation on succeeding
local or subordinate levels. Because of the
sensitive demands of human subject
protections, local authorities may require
stricter interpretations than those passed down
from higher authorities. Stricter
interpretations always take precedence.
31
Basic Principles Regulatory Documents
45 CFR 46 (Originally promulgated in
1974) Requirements for DHHS/NIH and their
awardees. The Common Rule Federal Policy of
1991 Requirements for 16 federal agencies and
their awardees detailed in various CFR sections
e.g. DoD - 32 CFR 219 VA - 38 CFR 16 DOE - 10
CFR 745 etc. 21 CFR 50 and 21 CFR
56 Requirements for FDA and related regulatory
requirements.
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Basic Principles Regulatory Documents (contd)
Agency Directives Agencies should develop local
instructions to implement all higher agency
requirements. Guidebooks Standard Operating
Procedure Manuals Should be developed on the
local level to assist investigators and
committees for proper initial, continuing and
final review of all protocols involving the
enrollment of human subjects.
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Basic Principles Regulatory Documents A Final
Word..
To understand the critical nature of human
subject protections and the various regulatory
and ethical requirements, investigators must be
well-versed in each of the regulatory documents
but especially those that contain agency-specific
regulations.
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Informed Consent
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INFORMED CONSENT
Informed consent is central to the protection of
human subjects. It is both a process and a
procedure. The process of informed consent takes
place in the professional interaction between
research or clinical staff and individual
enrollees. The procedure of informed consent
includes the shaping and signing of an informed
consent document.
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INFORMED CONSENT
Both the process and procedures of informed
consent always must include the following key
characteristics
Information Comprehension Voluntariness
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INFORMED CONSENT (contd)
Information Informed consent must provide clear
information regarding the research study,
location, procedures to be followed, potential
risks, possible benefits, duration of the study,
alternatives, confidentiality provisions,
contact information, and assurance of freedom to
withdraw without penalty.
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INFORMED CONSENT (contd)
Comprehension Informed consent must be obtained
in a way that is intelligent, rational and
respective of the maturity of enrollees. Consent
documents must be written in the native language
of enrollees, and in a way that is
non-technical/non-scientific. The informed
consent process and informed consent forms are
not for the benefit of the scientist.
They are for the subject!!!
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INFORMED CONSENT (contd)
Voluntariness Informed consent must preclude
any element or even the appearance of coercion
or undue influence.
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INFORMED CONSENT Critical Elements 45 CFR 46
A) Basic Elements of Informed Consent Required
in all studies

• 1. A statement that the study involves research,
  an explanation of
• the research, and the expected duration of the
  subjects participation,
• a description of the procedures to be followed,
  an identification of
• any procedures that are not experimental
• 2. A description of any reasonably foreseeable
  risks or discomforts
• to the subject
• 3. A description of any benefits to the subject
  or to others, which may
• reasonably be expected from the research
• 4. A disclosure of appropriate alternative
  procedures or courses
• of treatment, if any that might be advantageous
  to the subject

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INFORMED CONSENT Critical Elements (contd)
5. A statement describing the extent, if any, to
which confidentiality of records identifying the
subject will be maintained 6. For research
involving more than minimal risk, an
explanation as to whether any compensation and/or
medical treatment are available if injury occurs
and, if so, what they consist of, or where
further information may be obtained 7. An
explanation of whom to contact for answers to
pertinent questions about the research and
research subjects rights, and whom to contact in
the event of a research-related injury to the
subject.
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INFORMED CONSENT Critical Elements (contd)
8. A statement that participation is voluntary,
refusal to participate will involve no penalty or
loss of benefits to which the subject is
otherwise entitled, and the subject may
discontinue participation at any time without
penalty or loss of benefits to which the subject
is otherwise entitled.
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INFORMED CONSENT Critical Elements (contd)
B) Additional Elements of Informed Consent If
deemed appropriate by the IRB.

• 1. A statement that the particular treatment or
  procedure may involve
• risks to the subject (or to the embryo or fetus,
  if the subject is or may
• become pregnant) which are presently
  unforeseeable
• 2. Anticipated circumstances under which the
  subjects participation
• may be terminated by the investigator without
  regard to the subjects
• consent
• 3. Additional costs to the subject that may
  result from participation
• in the research

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INFORMED CONSENT Critical Elements (contd)
4. The consequences of a subjects decision to
withdraw from the research and procedures for
orderly termination of participation by the
subject without prejudice to the subject. In all
instances where abrupt withdrawal would be
hazardous to the subject (e.g, medication
regimens which require gradual reduction)
appropriate safe discontinuation procedures will
be followed and the subject advised 5. A
statement that major new findings developed
during the course of the research, which may
relate to the subjects willingness to continue
participation, will be provided to the subject
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INFORMED CONSENT Critical Elements (contd)
6. The approximate number of subjects involved in
the study and 7. A statement that informs the
subject that the Food and Drug Administration
(FDA) may inspect the research records in
projects where this is applicable.
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IRB Systems
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IRB Systems
PURPOSE To ensure that human subjects research
is ethically acceptable and in accordance with
all regulatory requirements. The Code of Federal
Regulations has established Institutional Review
Boards (IRB) for the initial, continuing and
final review and monitoring of all human subject
research protocols. In its various sections, the
Code also details requirements for IRB
membership, authority, responsibilities and
related IRB procedures and other matters.
cf. The Common Rule 45 CFR 46 21 CFR 56
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IRB Systems
DEFINITION As would be applicable for medical
research, 21 CFR 56.102 contains a clear
definition of an IRB Institutional Review
Board (IRB) means any board, committee, or other
group formally designated by an institution to
review, to approve the initiation of, and to
conduct periodic review of, biomedical
research involving human subjects. The primary
purpose of such review is to assure the
protection of the rights and welfare of the
human subjects.
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IRB Systems
Basic Composition 45 CFR 46.107 A minimum of
FIVE members One must be unaffiliated One
must be a non-scientist. There are some
complicating special issues with forming an
IRB membership Federal rules, medical context,
social and behavioral contexts, mix of
disciplines etc. Major Issue Resourcing IRBs
in institutions --- personnel, funds,
logistics etc.
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IRB Systems
IRB Review and Approval Notation
Approval and the Initiation of Research
The enrollment of subjects and all research
activities related to the enrollment of subjects
cannot begin until final approval has been given
in writing by the appropriate approval authority.
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IRB Systems
IRB Responsibilities
To ensure the protection of human subjects from
research risks, each IRB has the following clear
responsibilities for protocol assessment and
reviews 1. To Interpret And Implement Federal
Regulations 2. To Assure that all IRB standards
are met 3. To Assess the Level of Risk 4. To
Assure Proper Informed Consent 5. To Provide
Continuing Review of Research 6. To Maintain
Records and Confidentiality.
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IRB Systems
Determining Level of Risk The IRB must determine
the level of risk for each protocol according to
the following schema.
1. Exempted Research Protocols that qualify
under the CFR (e.g. 32 CFR 219 or 45 CFR 46) as
exempt from IRB regulations. 2. Minimal Risk
Protocols wherein the risk to volunteers is no
greater than in routine daily activities or in
routine physical exams. 3. Greater than Minimal
Risk Protocols wherein the risk to volunteers is
greater than routine daily activities or routine
physical exams.
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IRB Systems
Expedited Review
Expedited review is a permissible procedure under
the Code of Federal Regulations for a simpler
review of protocols by an IRB Chair or subgroup
of the committee when risks are considered
extremely minimal.
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IRB Systems
Criteria for IRB Recommendation for Approval
All risks to subjects are minimized. All risks
to subjects are reasonable compared to the
anticipated benefits of the research. ...Selecti
on of subjects is equitable. Requirements for
informed consent standards are met. This includes
certifying that the process of informed consent
is adequate for the situation, and that the
informed consent forms meet the need and contain
all critical elements.
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IRB Systems
Criteria for IRB Recommendation for Approval
(contd)
...Adequacy of plan for monitoring data is
assessed and guaranteed. ...Privacy of subjects
is protected and confidentiality of data is
maintained. ... Vulnerability of subjects to
coercion or undue influence is safeguarded.
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IRB Systems
Investigator Requirements for Protocols
Completed protocol in line with recommended
format. Scientific Review completed/certified
prior to IRB submission. Submission to IRB for
review/action/approval processes. Timely
submission of modifications for approvals as
needed.
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IRB Systems
Investigator Requirements for Protocols (contd)
Timely reporting of complications, adverse
events and serious adverse events according to
all regulations. Prompt submission of
continuing reviews as directed but minimally once
a year. Prompt submission of final report
within required deadline after completion of the
protocol.
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IRB Systems
Continuing or Periodic Review Requirements
...Federal regulations mandate that all IRB
protocols receive continuing review at least
once a year. A required format should be used.
The IRB is free to require more frequent
reviews. Protocols not receiving at least
annual review lose authorization for
research. Non-compliance requires immediate
action. In many cases, continuing reviews
require extensive critique of informed consent
forms/processes and protocol monitoring
results. ...Exempted protocols should require
continuing review reports not reviewed by the
IRB but only by the Chair. Reassess risk! ...All
protocols require a detailed final report within
90 days after completion of the protocol itself.
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Education, Training and Certification
The intricacies surrounding the protection of
human subjects from research risks require a
commitment to continuing education and on-going
investigator and staff training. IRB Members and
Leadership have a particular responsibility to
continuing education for professional service.
Note well regarding NIH
Grants Key research personnel, as of 01 October
2000, are required to demonstrate completion of
intramural agency education and training before
an NIH grant will be awarded. This sets up a new
paradigm for institutional compliance in terms
of IRB certifications and credentialing.
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Conclusion IRB Ethics The Ethos of Research
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IRB Ethics Revealing the Ethos of Research
Discerning parameters regarding human research is
not simply a matter of regulatory or legal
compliance. It is a matter of ethics. Research
ethics arises directly from the ethos of a
culture and its communities of inquiry!
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IRB Ethics Revealing the Ethos of Research
The REAL goals of medical research.. Scientific
and Social Progress Increasing the Quality of
Life Equal Sharing of Risks and
Benefits Preserving Patient Dignity,
Confidentiality and Safety These
are not Pollyanna. These are the very stuff of
human desire and longing (cf. Freud/Jung)
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IS IT WORTH IT?

• Detriments
• Potential liability
• Great Responsibility
• Increased workload
• Benefits
• Educates the librarian about the types of
  research
• being conducted
• Increases knowledge of the research process at
  your institution
• Facilities decision-making and improvement of
• library services
• Networking and increases access to
• administration
• Adds to the value of the research librarian
  and,
• their facility, and highlights the importance of
  both
• Personal satisfaction of helping patients and
• promoting clinical research at your institution

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IRB Ethics RESPECT BENEFICIENCE JUSTICE
Protecting the rights and welfare..
of those who further the genius of research.
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If your experiment needs statistics, you ought
to have done a better experiment.
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There are three kinds of lies lies, damned lies
and statistics!