Marshall University
Huntington ,
WV
SUBJECT: Risk –
Benefit
PURPOSE: To establish
guidelines for the Institutional Review Board (IRB) to assess the risks and
benefits in human subject research activities.
POLICY: To systematically
evaluate the overall level of risk and anticipated benefits as part of the
initial review and continuing review of all research involving human
subjects.
SCOPE: This policy covers
all research involving human subjects.
RESPONSIBILITIES:
Institutional Official – As the Institutional Official (IO),
the Marshall University Vice President for Research has the ultimate
responsibility to ensure the rights and safety of human subjects are
protected. The Institutional
Official delegates the authority to the IRB to systematically evaluate the
overall risks and benefits for the human subjects to assure they are
protected.
Chairperson – The Chairperson has the
responsibility to ensure all research involving human subjects is systematically
evaluated as to the risks and benefits.
No research activity will be approved where the risks are not reasonable
in relation to the benefits to the subject and the knowledge to be gained. The Chairperson assures continual
monitoring of the risks and benefits throughout the research activity. The Chairman
is responsible for reporting any serious unanticipated problems involving risks
to subjects or others to the Director, ORI and to any applicable sponsors or
agencies.
Members – The members have the responsibility to systematically evaluate all research involving human subjects as to the risks and benefits involved and only approve those research activities that are reasonable in relation to the benefits. Therefore, scholarly or scientific review of proposed research should answer the following questions:
(1) Does the research use procedures consistent with sound research design?
(2) Is the research design sound enough to reasonably expect the research
to answer its proposed question?
(3) What is the importance of the knowledge
expected to result from this research?
Principal Investigator (PI) – The
Principal Investigator has the responsibility to present his true evaluation of
the risks and benefits of the research activity and he must report any new information
concerning risks to the human subjects promptly to the IRB. The PI is responsible for ensuring and
documenting that the patient can differentiate between those activities that are
therapeutic in nature from research activities.
IRB Coordinator – The IRB Coordinator has the
responsibility to ensure all risks identified are properly documented in the IRB
minutes and for preparing any reports to higher level authorities or
agencies.
DEFINITIONS:
Risk is an injury to safety, rights, or
welfare and it is expressed in terms of probability, magnitude, and
permanency. The four types of risk
are physical, economic or financial, social and
psychological.
(1) Physical risk – actions and situations
that result in bodily harm
(2) Economic or financial risk – loss of
privacy could lead to loss of benefits, insurance, or employment.
(3) Social - specific uses of information could
hurt the subject’s social position or could be harmful to groups of subjects in
their community.
(4) Psychological - deception or mishandling of information could cause psychological trauma.
Legal Risk - the risk that a research participant's sharing of information may be self-incriminating, resulting in civil or criminal liability.
PROCEDURE:
The IRB must distinguish research that is greater than minimal risk from research that is no greater than minimal risk when considering human subject research activities. Research that is no greater than minimal risk may be eligible for expedited review, waiver or alteration of informed consent requirements, or waiver of the requirement to obtain written documentation of consent (Waiver of informed consent is not generally appropriate for FDA regulated test articles.)
Minimal
risk
means that the probability and magnitude of harm or discomfort in the research
are not greater in and of themselves than those encountered in daily life or
during the performance of routine physical or psychological examinations or
tests.
To
approve a research activity, the IRB must comply with the following regulatory
criteria:
(a) In order to approve research covered by these regulations the IRB shall determine that all of the following requirements are satisfied:
(1) Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.
(2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies that subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.
(3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons.
(4) Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with and to the extent required by part 21 CFR §50.20, 21 CFR §46.116, and 38 CFR §16.116.
(5) Informed consent will be appropriately documented, in accordance with and to the extent required by 21 CFR §50.27, 21 CFR §46.117, and 38 CFR §16.117.
(6) Where appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
(7) Where appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
(b) When some or all of the subjects, such as children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons, are likely to be vulnerable to coercion or undue influence additional safeguards have been included in the study to protect the rights and welfare of these subjects.
(c) In order to approve research in which some or all of the subjects are children, an IRB must determine that all research is in compliance with part 21 CFR §50, subpart D.
Criteria That The IRB Uses To Determine Which Research Requires Review More Often Than Annually. The IRB will require review more often than annually when any of the following are true:
-
Procedures not before used in humans.
-
More than minimal risk to vulnerable populations with no prospect of direct benefit.
-
A high likelihood that participants will die due to the research procedures.
-
Any other reason for which the IRB wants closer monitoring.
In specifying an
approval period of less than 1 year, the IRB may define the period with either a
time interval or a maximum number of subjects, (i.e., after 3 months or after
three subjects). The IRB will
determine the time interval or number of subject and the IRB minutes will clearly reflect these determinations regarding risk
and approval period.
Criteria That The IRB Uses To Determine Which Research Requires Verification From Sources Other Than The Investigator That No Material Changes Have Take Place Since The Last IRB Review. The IRB will get verification from sources other than the investigator that no material changes have taken place since the last review when any of the following are true:
-
The information provided by the investigator is internally inconsistent or inconsistent with other information known to the IRB, and the inconsistency cannot be resolved through communication with the investigator.
-
The IRB doubts the information provided by the investigator.
-
The investigator has a history of non-compliance with continuing review.
-
Any other reason for which the IRB wants verification.
If yes, then verification must be obtained from sources other than the investigator that not material changes have occurred since the last IRB review.
The IRB can obtain verification that no material changes have taken place since the last review by audit or official notification from the institutional official of the site in which the research is being conducted.
Continual Review.
The IRB continually reviews
Serious Adverse Events (SAE) reports, sponsor safety reports, changes in the
investigator brochures, changes to the research, including amendments to the
protocol, any information that may change the risk/benefit ratio, most recent
findings, including summary of subject experiences (benefits, adverse reactions)
and summary of DSMB meetings (if applicable), reports of injuries to subjects,
unanticipated problems involving risks to subjects and subjects withdrawn and
the reasons for withdrawal.
Privacy
and Confidentiality
Certificates
of Confidentiality. Where research involves the collection
of highly sensitive information about individually identifiable subjects, the
IRB may determine that special protections are needed to protect subjects from
the risks of investigative or judicial processes. In these situations the IRB
may require that an investigator obtain a Department of Health and Human
Services (DHHS) Certificate of Confidentiality (CoC). For
studies not funded by DHHS, if there is an Investigational New Drug Application
(IND) or an Investigational Drug Exemption (IDE), the sponsor can request a
CoC from the FDA. The CoC
protects against the involuntary release of sensitive information about
individual subjects for use in Federal, state, or local civil, criminal,
administrative, legislative, or other legal proceedings. The CoC does
not prohibit voluntary disclosure of information by an investigator, such as
voluntary reporting to local authorities of child abuse or of a communicable
disease. In addition, the CoC does not protect against the release of information to
VA, DHHS or FDA for audit purposes.
The IRB requires that these conditions for release be stated clearly in
the informed consent document.
Safeguards for Vulnerable Subjects. The IRB must determine that additional safeguards have been included to protect the rights and welfare of subjects who are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, persons with mental disabilities, or economically or educationally disadvantaged persons.
The IRB pays special attention to the following specific
elements of the research plan when reviewing research involving vulnerable
subjects:
(1)
Inclusion and
exclusion criteria for selecting and recruiting subjects; informed consent
and willingness to volunteer; coercion and undue influence; and confidentiality
of data.
(2)
Group characteristics,
such as economic, social, physical, and environmental conditions, to ensure that
the research incorporates additional safeguards for vulnerable
subjects.
(3)
Adequate procedures in
place for assessing and ensuring subjects’ capacity, understanding, and informed
consent or assent. When weighing
the decision whether to approve or disapprove research involving vulnerable
subjects, the IRB looks to see that such procedures are a part of the research
plan. In certain instances, it may
be possible for researchers to enhance understanding for potentially vulnerable
subjects. Examples include
requiring someone not involved in the research to obtain the consent, the
inclusion of a consent monitor, a subject advocate, interpreter for
hearing-impaired subjects, translation of informed consent forms into languages
the subjects understand, and reading the consent form to subjects slowly and
ensuring their understanding.
(4)
The IRB is required to
document specific findings to minimize the potential for risk or harm to the
fetus, and additional attention must be given to the conditions for obtaining
informed consent.
Compensation
for Injury. The IRB ensures that subjects are
provided with accurate information about the availability of compensation and
treatment for injury occurring in the research that it reviews. However, this requirement does not
apply to (1) treatment for injuries due to non-compliance by a subject with
study procedures; or (2) research conducted for
Review of Reports of Unanticipated Problems or Serious Adverse Events (SAE). Refer to the Adverse Events/Serious Adverse Events SOP.
Suspension or Termination of IRB Approval of Research. 45 CFR §46.113 states the following:
"An
IRB shall have authority to suspend or terminate approval of research that is
not being conducted in accordance with the IRB's requirements or that has been
associated with unexpected serious harm to subjects. Any suspension or
termination of approval shall include a statement of the reasons for the IRB's
action and shall be reported promptly to the investigator, appropriate
institutional officials, and the department or agency head."
Definitions:
Suspension of previously approved research. Suspension of IRB approval: An action taken by the IRB to temporarily or permanently withdraw approval for some or all research activities short of permanently withdrawing approval for all research activities.
Termination of previously approved research. Termination of IRB approval: An action taken by the IRB to permanently withdraw approval for all research activities.
Circumstances under which the IRB may suspend or terminate previously approved research:
-
When research is not conducted in accordance with IRB requirements.
-
When research is associated with unexpected serious harm to participants.
The IRB utilizes the following process to suspend or terminate previously approved research:
-
The IRB Chairperson is authorized to make suspension and termination determinations.
-
The IRB Chairperson will evaluate all possible suspensions and terminations on an urgent basis.
-
When a termination or suspension involves the withdrawal of current participants from the research:
(1) Enrolled participants will be notified;
(2) The withdrawal of enrolled participants must take into account their rights and welfare; and
(3) When follow-up of participants for safety reasons is permitted or required, participants will be so informed and any adverse events or unanticipated problems involving risks to participants or others will be reported to the IRB and others as required by the protocol and organizational policies and procedures.
It is the responsibility of the Director, ORI to provide prompt written notification to institutional officials and regulatory agencies when:
-
It has been determined that an incident of non-compliance is serious or continuing.
-
It has been determined that an event is an unanticipated problem.
-
The IRB suspends or terminates its approval of research.
The Director, ORI is also responsible for the reporting of:
-
All events involving VA research to the VA Research and Development Office and the regional VA Office of Research Oversight.
-
Unauthorized use, loss, or disclosure of individually.
-
Violations of information security requirements to the appropriate Information Security Officer.
Social and Psychological Harms. Behavioral and Social Sciences research often involves surveys, observational studies, personal interviews, or experimental designs involving exposure to some type of stimuli or intervention. IRB carefully determines the probability of risk of harm to subjects and considers the following:
(1)
The potential for
subjects to experience stress, anxiety, guilt, or trauma that can result in
genuine psychological harm.
(2)
The risks of criminal
or civil liability or other risks that can result in serious social harms, such
as damage to financial standing, employability, insurability, or reputation;
stigmatization; and damage to social or family
relationships.
(3)
If information is
being collected on living individuals other than the primary “target” subjects
and the risk of harm to those “non-target” individuals, as
well.
To mitigate such risks, IRB reviews the proposal for appropriate preventive protections and debriefings, adequate disclosure of risks in the informed consent information, and mechanisms to protect the confidentiality and privacy of persons participating in or affected by the research.
Privacy and Confidentiality Concerns. For information concerning this topic refer to the Confidentiality SOP.
Safeguarding Confidentiality. For information concerning this topic refer to the Confidentiality SOP.
Research Involving Deception or Withholding of Information. The reviewing of research involving incomplete disclosure or outright deception must apply both common sense and sensitivity to the review. Where deception is involved, the IRB needs to be satisfied that the deception is necessary and that, when appropriate, the subjects shall be debriefed. (Debriefing may be inappropriate, for example, when the debriefing itself would present an unreasonable risk of harm without a corresponding benefit.) The IRB should also make sure that the proposed subject population is suitable. Deception can only be permitted where the IRB documents that a waiver of the usual informed consent requirements is justified under the criteria present in regulations. Specifically, the IRB must find and document that all four of the following criteria have been satisfied:
(1)
The research presents
no more than minimal risk to subjects.
(2)
The waiver or
alteration shall not adversely affect the rights and welfare of the
subjects.
(3)
The research could not
practicably be carried out without the waiver or
alteration.
(4) Where appropriate, the subjects shall be provided with additional pertinent information after participation.
(5) The research does not involve non-viable neonates.
(6) The research is not subject to FDA regulation.
In making the determination to
approve the use of deception under a waiver of informed consent, the IRB will
consider each criterion in turn, and document specifically (in the minutes of
its meeting and in the IRB protocol file) how the proposed research satisfies
that criterion. (Note: The regulations make no
provision for the use of deception in research that poses greater than minimal
risks to subjects).
Research Involving Potentially Addictive Substances. Research involving potentially addictive substances often
involves the use of what may be termed “abuse-liable” substances. Abuse-liable substances are
pharmacological substances that have the potential for creating abusive
dependency. Abuse-liable substances
can include both legal and illicit drugs.
The following are among the issues that the IRB should consider when
reviewing research involving potentially addictive
substances:
(1)
The subjects’ capacity
to provide continuous informed consent, ensuring that subjects are
competent and
are not coerced.
(2)
If such research
involves subjects that are institutionalized, the subjects’ ability to exercise
autonomy could
be impaired.
(3)
Consider the
requirements for equitable selection of subjects and protections for
maintaining
confidentiality, as such a population may be at risk for being discriminated
against, or
over-selected.
(4)
Be sensitive to the
ethical context of the research, in that there may be moral dilemmas
associated with
the use of placebos, or in cases where addicts are presented with alcohol
or
drugs.
It is critical that the IRB focus on the considerations of
risk and benefit of such research.
Follow Up Responsibility:
Director, Office of Research
Integrity
References: 38 CFR
16
45 CFR 46
38 CFR 17
Common Rule
Privacy Act of 1974.
Revised 5-1-2007