5. Risk/Benefit Assessment
Investigators submitting research proposals for HSPC review
should understand that the Committee is responsible for assessing
the risks vs. anticipated benefits of research as one of its
primary functions. In addition, once risks and benefits have been
assessed, the HSPC is responsible for ensuring that the risks of
study participation are minimized to the greatest extent possible
while the benefits of study participation are maximized. This is
clearly stated in all codes of research ethics and is
incorporated throughout the federal regulations that govern the
HSPC.
The following definitions of risk, minimal risk and benefit,
which are used to assess risks and benefits as they pertain to
research conducted at UCLA, are defined by the DHHS as follows:
Risk: The probability of harm (physical,
psychological, social, or economic) occurring as
a result of participation in a research study.
Both the probability and magnitude of possible
harm may vary from minimal to significant. The
federal regulations define only "minimal
risk" (see below). Minimal Risk: A
risk is minimal where the probability and
magnitude of harm or discomfort anticipated in
the proposed research are not greater, in and of
themselves, than those ordinarily encountered in
daily life or during the performance of routine
physical or psychological examinations or tests [45
CFR 46.102(i)].
Benefit: A valued or desired outcome;
an advantage.
Although these terms may appear straightforward, evaluations
of risk and benefit are made more complex both by subtle
distinctions between therapeutic and research activities, and by
evaluations of actual risks in the lives of normal and vulnerable
classes of subjects (i.e., prisoners, children,
cognitively impaired individuals, etc.).
It is important for investigators to understand that the
comparison between risks and benefits is not a comparison between
identical concepts. Because the term "Risks" is
normally expressed as probabilities while the term
"Benefits" is normally expressed as fact or a current
state of affairs, investigators may find it difficult to compare
these concepts in a meaningful fashion. Therefore, it is more
convenient for researchers to think of these terms as evolving
probabilities. For example, the risks of participation in
research can be expressed as a probability that subjects may be
harmed by research procedures while anticipated benefits may
express the probability that subjects and society may benefit
from research procedures. By considering risks and benefits as
probabilities, the HSPC evaluation process is also simplified.
HSPC
Considerations
There are a number of steps discussed by the DHHS that the
HSPC must follow when assessing risks and anticipated benefits.
The HSPC is required to:
- identify the risks associated with the research, as
distinguished from the risks of therapies the subjects
would receive even if not participating in the research;
- determine that the risks will be minimized to the extent
possible;
- identify the probable benefits to be derived from the
research;
- determine that the risks are reasonable in relation to
the benefits to subjects, if any, and the importance of
the knowledge to be gained;
- assure that potential subjects will be provided with an
accurate and fair description of the risks or discomforts
and the anticipated benefits;
- determine intervals of periodic review, and, where
appropriate, determine that adequate provisions are in
place for monitoring the data collected, and, where the
subjects are likely to be members of a vulnerable
population, determine that appropriate additional
safeguards are in place to protect the rights and welfare
of these subjects.
Because the HSPC is required to follow the above listed
procedures, investigators should address these considerations in
their consent form.
Identification
and Assessment of Risks
When considering risks, the HSPC considers only those risks
associated with the research (i.e., physical,
psychological, social, legal, emotional). Investigators should be
aware that risks would include immediate risks of study
participation, risks of randomization (especially to placebo
groups), risks of breach of confidentiality, and risks of long
term effects.
For biomedical research, the HSPC is required to determine and
differentiate between the risks associated with the research and
the risks associated with standard diagnostic or therapeutic
interventions or therapies subjects would undergo regardless of
participation in research. Since the HSPC does not establish or
determine what constitutes standard of care, it is important for
investigators to clearly distinguish procedures which are
standard of care from those which are conducted solely for
research purposes in the protocol and the informed consent form.
Physical
Risks
Some biomedical research presents risk of physical injury to
subjects. Although most of these risks are transient, some
adverse effects of study participation (especially those which
result from medical procedures, drug research or device research)
may result in permanent injury to subjects. For all research with
the potential to cause physical harm investigators are encouraged
to think through all risk possibilities, however rare, so that
they can be resolved quickly and effectively minimize the harm to
subjects. By clearly detailing procedures to address situations
of physical harm, the HSPC can be assured that the investigator
has made efforts to minimize physical risks to the greatest
extent possible.
Psychological
Risks
Some research has the potential to cause undesired changes in
thought processes and emotion including episodes of depression,
confusion, hallucination resulting from drugs, feelings of
stress, guilt and loss of self-esteem. As is the case with
physical risks, these effects are usually transient. For all
research with the potential to cause psychological harm
investigators are encouraged to think through all risk
possibilities, however rare, so that a course of action can be
planned to quickly and effectively minimize the distress to
subjects. By clearly detailing procedures to address situations
of psychological harm, the HSPC can be assured that the
investigator has made efforts to minimize psychological risks to
the greatest extent possible.
Social and
Economic Risks
Some research proposals involve the handling of sensitive
information which may result in injury to subjects through a
breach of confidentiality. These breaches may result in
embarrassment within a subject’s business or social group,
loss of employment, or criminal prosecution. The HSPC is
especially concerned about information regarding drug and alcohol
use, mental illness, sexual behavior and illegal activities. For
these situations investigators should clearly detail strong
safety precautions to ensure that the research does not cause
social or economic risks to the subjects.
Research may also pose direct economic risk to study subjects.
Procedures billed to insurance companies may require a
significant co-payment on behalf of the subjects, insurance
companies may refuse to pay for "investigational"
therapies, subjects may be responsible for transportation costs,
and subjects may lose wages during research participation.
Investigators should attempt to minimize economic costs to
subjects. If the research may involve additional actual costs to
individuals, the anticipated costs should be described to
subjects during the consent process.
Minimal Risk
Much of the HSPC review process is governed by the concept of
minimal risk. Assignment of research for expedited review,
approval of waiver of consent, and the conduct of research
involving vulnerable research populations may be dependent upon
whether the research places subjects at minimal risk or greater
than minimal risk (significant risk). Investigators should note
that studies proposing procedures which pose less risk than
standard procedures may not necessarily be determined to be of
minimal risk to subjects. Investigators should pay particular
attention to the term minimal risk as it is applied throughout
this manual. NOTE: When the risks are unknown, they are
considered more than minimal.
Benefits
The benefits of research fall into two categories: benefits to
individuals and benefits to society.
Research frequently provides subjects with treatment,
diagnosis or examination for an illness or abnormal condition. In
these cases the research involves evaluations that may benefit
the subjects by ameliorating their condition or provide a better
understanding of their disorder. Investigators should clearly
detail these potential benefits for the HSPC, in the application,
and subjects, in the consent form, while not overstating these
benefits. The investigator should also attempt to maximize
benefits to the greatest extent possible for potential subjects.
Although research may not always provide a benefit to society,
researchers are encouraged to design research projects so that
information, in the form of generalizable knowledge, can
contribute to societal benefit whenever possible. Investigators
should clearly detail these potential benefits for the HSPC, in
the application, and for subjects, in the consent form, while not
overstating these benefits. Research which does not provide
benefit to individuals is required to provide a reasonable
likelihood of resulting in benefits for society.
Contact OPRS
October 29, 2004
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