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THE COMMITTEE ON HUMAN RESEARCH
History and
Composition
Since 1966, the United States Department of Health
and Human Services (DHHS), formerly called the Department of Health,
Education and Welfare (DHEW), has required prior review and approval
of all research using human subjects that is funded by federal agencies.
In 1970, the President of the University of California required that
U.S. Public Health Service Regulations apply to "all investigations
involving human subjects for which the University is responsible." This
policy was re-stated in 1981.
DHEW issued its "Institutional Guide to DHEW Policy on Protection
of Human Subjects" in December of 1971. Subsequently, the University
of California made the DHEW policy applicable to all human subject activities
conducted by or under the direction of University employees, regardless
of the source of funding or even when no funds are involved. DHEW guidelines
were revised and made regulation in 1974. Between 1974 and 1978, the
National Commission on Protection of Human Subjects of Biomedical and
Behavioral Research met and issued a series of reports and recommendations
resulting in revised regulations issued by DHHS in January of 1981. The
United States Food and Drug Administration (FDA) was simultaneously developing
its own regulations, which were also issued in January of 1981 and have
since been revised, most recently in October 1996. DHHS issued revised
regulations in March of 1983 and again in June of 1991. These regulations,
which provided standards for review of human research activities by institutional
review boards now apply to all activities involving human subjects within
the University.
The
Committee on Human Research (CHR), which is the University of California,
San Francisco's institutional review
board (IRB), was created in 1966, and re-structured in 1971. The
campus holds an approved Federalwide Assurance
(FWA) from DHHS. This is a written agreement in which UCSF describes
the jurisdiction, composition, and methods of procedure by which
the CHR will function, and the in the DHHS approves
it. This FWA was most recently reapproved in 1995 2003.
The CHR is regularly
audited by the FDA and may be audited by other offices at DHHS
(e.g., OPRR, NCI, SWOG, PCRC). The Committee members are appointed
by the Executive
Vice Chancellor.
The Committee and typically consists of about 15 members, of whom
a majority are physicians from a wide range of disciplines. The other
members represent
fields such as clinical nursing, pharmacy, the social and behavioral
sciences, law, and theology. At least one community member, not
affiliated with UCSF, always serves on the Committee.
At present, there are three IRB panels at UCSF. The
three panels together are called the Committee on Human Research (CHR).
The
CHR was first created in 1966 and then restructured in 1971, both
times with
one panel. By 1980 that one panel met every week throughout the
year. In 1997 a second panel was added, with each panel meeting
twice a month.
In 2002 a third panel was added, again, with each panel meeting
twice a month. The UCSF CHR reviews research being conducted not
only at UCSF,
including UCSF at Fresno, but also at the Veterans Affairs Medical
Center, San Francisco General Hospital, Gallo and Gladstone Institutes,
and the
San Francisco Department of Public Health. It also reviews some
research for the Blood Centers of the Pacific and various other
smaller institutions. The number of CHR applications reviewed
annually rose from fewer than 50 in 1966 to almost 500 in 1972, more
than 3400 in 1996, and more than
5300 in 2003. These numbers reflect all reviews of new, renewed
and modified studies (full committee and expedited applications). They
do not include
the review of exempt certifications, special requests, or adverse
event reports. At the close of 2003 there were approximately 3500 CHR-approved
studies. The federal government supports 38% of the total number
of human
research studies at UCSF and provides 78% of the total funding
for UCSF’s
human research. However, industry-sponsored studies are increasing
both in numbers and the amount of money awarded. There are about
four biomedical
studies to every one behavioral study reviewed.
A Quality Improvement Unit was established in late 2002 to help improve
and assure the quality of human research at UCSF. This unit in conjunction
with the CHR are the two units that now comprise UCSF’s Human Research
Protection Program.
Charge
It is the duty of the CHR to review and make decisions on all protocols
for research involving human subjects. Its primary responsibility is
the protection of subjects from undue risk and from deprivation of personal
rights and dignity. This protection is best assured by consideration
of three principles which are the touchstones of ethical research: (1)
that voluntary participation by the subjects, indicated by free and informed
consent, is assured; (2) that an appropriate balance exists between potential
benefits of the research to the subject or to society and the risks assumed
by the subject; and (3) that there be fair procedures and outcomes in
the selection of research subjects. These principles are summarized as
respect for persons, beneficence, and justice in "The Belmont Report:
Ethical Principles and Guidelines for the Protection of Human Subjects
of Research" (National Commission for the Protection of Human Subjects
of Biomedical and Behavioral Research, April 1979).
At times these issues are quite clear, and at times they are extremely
difficult to evaluate. Researchers themselves should begin the process
by examining their own projects in light of these principles as they
prepare to seek CHR approval. The CHR, in turn, brings to bear its collective
experience in reviewing each proposal, always conscious of its primary
responsibility to protect the rights of human subjects against exploitation,
but within the context of the need for continued scientific and human
progress.
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Respect for Persons: The Voluntary Participation of Experimental Subjects
One of the most important elements in any research involving
human subjects is assurance of free and informed consent. Any
person who is
to be a subject of research, whether designed for his/her
own direct benefit or for the advancement of scientific knowledge
in general, must
understand as completely as possible what is to be done
and what the potential risks and benefits are. The person must
give his/her
consent
freely, without pressure or inappropriate inducement. The
CHR attempts to ensure free and informed consent of subjects
through
careful review
of the recruitment and consent process, and of the consent
form or information sheet to be used with subjects.
The informed consent concept is extended to those studies
in which subjects are not able to give personal consent
for themselves. Here the
consent document is addressed to those who have
been designated
responsible for the subject's well-being (e.g.,
parents for children). The Committee's
concern is to verify that the consent process and
document are likely to assist these persons to make an informed
decision which is in the
best interests of the subject.
The capacity for truly informed and voluntary participation
in research varies widely among study populations.
At one extreme there
may be ample understanding and manifest freedom
from coercion; at the other, total absence of capacity
for personal
consent.
In between, there
are many degrees of understanding and freedom that
affect the consent of potential subjects. The Committee
must exercise special care when considering subjects whose ability to give free
and informed consent may be compromised in any way. (Consent
considerations and application requirements for such subject groups are discussed
further in Special Subject Populations).
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Beneficence: The Risk-Benefit Ratio
The CHR is charged with
deciding, for any proposed activity which falls under its jurisdiction,
whether: "The risks to the subject
are so outweighed by the sum of the benefit to the subject and
the importance of the knowledge to be gained as to warrant a decision
to allow the subject
to accept (those) risks " (Federal
Register, May 30, 1974).
The assessment of the risk/benefit relation is a complex
task. There are risks of injury or discomfort to the individual
that can be physical, psychological and/or social. There can be potential
benefits
to the individual, to a group to which the individual belongs,
and/or to society. In reviewing applications, the Committee must
carefully assess
the types and degrees of both risks and benefits for a given
subject population, as well as the investigator's communication
of these
risks and benefits in the consent process and form.
While the CHR is not charged with reviewing scientific
design per se, it must sometimes do so in order to assess risk/benefit
ratio. If a study design does not seem adequate to attain the
stated
aim of
the
investigation, then no benefit can be anticipated from conducting
the study, and there is no justification for placing any subject
at risk, however minimal. Thus, the design of the study must
be sound, and
the
nature and likelihood of all risks and benefits must be made
clear in any application to the Committee.
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Justice: The Fair Selection of Research Subjects
Both the risks and the potential benefits of research should
be spread fairly among potential individual subjects and subject
groups. Study design and selection of subjects should avoid bias for
or against particular social, racial, sexual, or ethnic groups.
Sharing Research Risks: The guiding principle in the ethical
selection of subject groups is that any risks of the research should
fall
upon the groups who might benefit from the research. If the results
of a risky
protocol might benefit the general population, it would be unethical
to focus subject recruitment on vulnerable or disadvantaged groups
(institutionalized people or prisoners; patients at free clinics
primarily patronized by
people unable to afford other care) simply because they are easily
accessible or can be persuaded to participate. Groups already
burdened by other
factors should not also be burdened by an undue share of research
risks. Rather, attempts should be made to include a fair sampling
of the populations
who might benefit from a study. When research involves persons
whose autonomy is compromised, it is expected that the research
bear some direct
relationship to the conditions or circumstances of the subject
population.
In addition, groups fully able to consider research
risks and informed
consent should be asked to face research risks before more vulnerable
populations. Investigational drugs usually are tested in adults
before they are tested in children. Certain investigational drugs
and procedures
may be tested in healthy volunteers before being tested in patients.
Sharing Research Benefits: In recent years increasing
attention has been paid to the rights of various groups to be included
in
research. As individuals and through advocacy groups, many patients
have come to
insist on having access to experimental treatments as these experimental
treatments may potentially provide the best medical care available.
In addition, researchers, ethicists, and public officials have
recognized that because many clinical trials focussed primarily
on white male
middle-class
subject groups, the results of some trials were of questionable
value for members of other social, racial, sexual, and ethnic
groups. As a
result, both the Food and Drug Administration and the National
Institutes of Health now require that study design include as
broad a range of subjects
as feasible and ask that data be analyzed to uncover responses
that differ between groups. Where women of child-bearing potential
and pregnant or nursing women previously were routinely excluded from new drug
trials, it is now required that whenever possible these women
be asked to make
their own choices after being fully informed of the risks of
the research.
While in the past participation in research was viewed
as a burden, it is now often seen as a right. Many in society now believe
that only by participating in research can an individual or
a group of subjects expect to experience the benefits of the advances being made
in the biomedical and behavioral fields of research. This is
a major shift in public perception
of medical research.
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