Guide for Interpreting the Federal
Policy for the Protection of Human Subjects
For research
involving human subjects, a large majority of Federal
Agencies simultaneously published a regulation or
"Common Rule" on June 18, 1991 to regulate
the conduct or support of such research. The following
Interpretive Guide to the Federal Policy for the Protection
of Human Subjects or "Common Rule" was developed
by a working group of individuals who attend the Human
Subjects Research Subcommittee, Committee on Science,
National Science and Technology Council. It does not
necessarily represent the position of any of their
respective agencies.
How to Interpret the Federal
Policy for the Protection of Human Subjects or "Common
Rule"
(Part A) 2/2/99
This Interpretive Guide to
the Federal Policy for the Protection of Human Subjects
or "Common Rule" was developed by a working
group of individuals who attend the Human Subjects
Research Subcommittee, Committee on Science, National
Science and Technology Council. The document does
not necessarily represent the position of any of their
respective agencies.
Purpose
The purpose of this document is to clarify and provide
guidance on how to interpret selected aspects of the
Federal Policy for the Protection of Human Subjects
(Part A) sometimes called the Common Rule. The guidance
is not intended to be exhaustive, but to help deal
with a number of common concepts and issues often
raised in the human subjects protection process. Thus
it is intended to be used as a companion to the Common
Rule itself. In addition, institutions must adhere
to other laws and regulations applicable to their
human subjects research including state law, foreign
laws, and human subjects procedures of the Food and
Drug Administration (FDA.)
Empowerment, Flexibility
and Discretion of Institutions and IRBs.
Trust in the honest, conscientious judgment of the
human beings who serve on IRBs is pivotal to the entire
system of protection of research subjects. Indeed,
the system recognizes that there is no simple formula
to apply to ethical decisions, and instead it vests
the major responsibility of ethical decision making
with the IRB. IRB actions are to be based on ethical
principles (such as outlined in the Belmont Report.)
They should fully recognize that ethical decisions
involve a balance among such principles (such as respect
for persons, beneficence, and justice) along with
the importance of the knowledge that may reasonably
be expected to result from proposed research (the
requirement for which is itself grounded in the principle
of beneficence.) In order to carry out its mandate,
Institutions and IRBs are empowered with very wide
discretion within the bounds of the Common Rule. Recognizing
the very wide range of situations under which research
may occur, above all else, the IRB should strive to
do "the right thing" as it sees it. The
regulations allow considerable flexibility to serve
that purpose.
Institutions,
IRBs and investigators all have a serious role to
play. In the interest of promoting human subjects
protection, it is important for institutions and IRBs
to take a facilitative, collegial and educational
posture with respect to investigators rather than
a burdensome adversarial one. The IRB should encourage
investigators to embrace ethical behavior by acting
to facilitate ethical research and not be seen as
an obstacle to the conduct of research. To that end,
institutions and IRBs should promote education outreach
efforts, and are encouraged to use their broad discretion
to adopt creative administrative and other means to
reduce administrative burden and maximize attention
to the most important ethical issues.
What is Research Under the
Common Rule?
The Common Rule defines research as "... a systematic
investigation including research development, testing
and evaluation designed to develop or contribute to
generalizable knowledge." Further, as described
in the Belmont Report "...the term 'research' designates
an activity designed to test an hypothesis, permit conclusions
to be drawn, and thereby to develop or to contribute
to generalizable knowledge.... Research is usually described
in a formal protocol that sets forth an objective and
a set of procedures to reach that objective."
Thus a key
aspect of research is that there be a systematic design
in advance, generally utilizing a scientific approach
or protocol, for the definite purpose of contributing
to generalizable knowledge. Research can include a
wide variety of activities including: experiments,
observational studies, surveys, tests, and recordings
designed to contribute to generalizable knowledge.
It generally does not include such operational activities
as: medical care, quality assurance, quality improvement,
certain aspects of public health practice such as
routine outbreak investigations and disease monitoring,
program evaluation, fiscal or program audits, journalism,
history, biography, philosophy, "fact-finding"
inquiries such as criminal, civil and congressional
investigations, intelligence gathering, and simple
data collection or data collection for other purposes.
However, some of these activities may include or constitute
research in the specific circumstance where there
is clear advance intent to contribute to generalizable
knowledge with a formal scientific protocol.
Human Subject
This means a living individual about whom an investigator
obtains 1) data through intervention or interaction
or 2) identifiable private information. Intervention
includes physical procedures and manipulations of the
subject or the subjects environment for research purposes
and interaction includes communication between the investigator
and the subject. Private information includes information
about behavior in which an individual can reasonably
expect that no observation is taking place, or information
for specific purposes (such as a medical record) that
individuals can reasonably expect will not be made public.
Private information must also be individually identifiable
(i.e. the subject's identity is or may be readily ascertained
by the investigator or the subject's identity readily
associated with the information.)
Thus, simple
observational studies of public behavior (including
television and internet chat rooms) do not involve
human subjects as defined, because there is no intervention
or interaction and the behavior is not private. Also,
studies based on data collected for non-research purposes
do not constitute human subjects research unless individual
identity is readily identifiable. Examples include:
programmatic data such as service statistics, school
attendance data, crime statistics, election returns,
vital statistics, and pathologic specimens collected
for therapeutic purposes (where such information does
not readily identify individuals.) A number of the
specific exemptions in the Common Rule (see below)
further address some of these and similar situations.
Exemptions
Survey and certain similar research
- 101(b)(2). The Common Rule exempts such research except
in situations where each of two things occurs: first
the information would allow subjects to be identified
(either directly or through identifiers linked to the
subject) and second "any disclosure of the human
subjects responses outside the research could reasonably
place the subject at risk of criminal or civil liability
or be damaging to the subjects' financial standing,
employability or reputation." Thus, survey and
similar research under formal human subjects protection
is "covered" only when both privacy/confidentiality
might be compromised through identification and the
nature of the information disclosed is very sensitive.
In determining whether there might be a reasonable risk
or damage related to divulging the sensitive information
etc., it is not enough that there be merely some hypothetically
possible risk that can be construed. Rather the risks
resulting from disclosure must be readily appreciable
and significant.
Research
involving the collection or study of existing data
or specimens - 101(b)(4). "Existing" means
existing at the time the research is conducted. Some
Agencies interpret this to mean existing at the start
of the research and some Agencies include as "existing"
sources such as vital records routinely created on
an ongoing basis without alteration, even though some
may be created after the start of the research. This
research is exempt if these sources are publicly available
or if the information is recorded by the investigator
in such a manner that subjects cannot be identified
directly or through identifiers to the subjects. Thus
the key point is how the data are recorded. The research
would remain exempt if the investigator had access
to identifiable information (such as medical records)
but did not record identifiers. Moreover, consistent
with the definition of human subject, identification
need be readily ascertainable. Research would remain
exempt for example if identity is linked only by legitimate
encryption or other procedures that make it very difficult
for investigators to identify individuals.
Public Benefit
or Service Programs (101)(b)(5). This exemption to
study, evaluate or otherwise examine public service
or benefit programs is fairly broadly written. However,
it is generally interpreted to be limited to research
on the process or outcomes of service delivery (e.g.
programmatic research or operations research.) DHHS,
in fact interprets this exemption narrowly to apply
primarily to entitlement and "entitlement-like"
programs such as Social Security.
Waiver or Alteration of Informed
Consent
Section 116 (d) provides conditions for waiving or altering
the informed consent procedure for research involving
no more than minimal risk. A key condition is that "The
research could not be practicably carried out without
the waiver or alteration." The determination that
the research could not be practicably carried out is
not a matter of mere inconvenience to the research process.
Rather, there need be a plausible concern that either
the conduct or the findings of the research might be
adversely affected by the consent process. An adverse
effect might include a substantial delay or increase
in cost. Examples of situations where waiver or alteration
of informed consent may often be justified are minimal
risk (and non-exempt) social science methods involving
deception; and surveys and cultural anthropology where
implementation of all or part of the informed consent
process might offend or raise unwarranted suspicions
among respondents - thereby adversely affecting the
research. Certain medical record review research is
another common example where consent may not be practicable.
Section 117 (c) allows for waiver of a signed consent
form under certain circumstances, but does not otherwise
alter the consent requirements per se.
Informed Consent to Promote Communication
Recognizing that communication is an imperfect human
process, in the interest of better human subjects protection,
it is important to recognize the informed consent process
as a process of communication and not just a legal requirement.
The consent form should not be confused with the informed
consent process. In the interest of good communication,
the process should promote: simple understandable language;
emphasis on the required and most important information,
and avoidance of "information overload," without
large amounts of additional information of marginal
use to the consent process. The process should also
promote good communication techniques such as active
listening, individualizing and requesting restatement
by the subject.
Minimal Risk
As defined in the Common Rule this "... means
that the probability and magnitude of the harm or
discomfort anticipated in the 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."
More specifically it means the risks encountered inherent
to the daily lives of the population or class of research
subjects involved and the additional of risk added
by the research. Thus, a treadmill test of low intensity
might be minimal risk for the population in general,
but more than minimal risk for research conducted
with a group of cardiac patients. Likewise, measuring
blood levels of a drug with serious side effects among
a group of patients already receiving it for therapy
might be considered minimal risk, whereas administering
the same drug solely for research purposes and measuring
it among the healthy population could be more than
minimal risk. This standard should not be interpreted
to mean that additional highly risky or potentially
harmful interventions are considered minimal risk
for certain severely ill patients simply because such
patients are subject to such interventions as part
of their treatment. Many nonexempt surveys may be
considered minimal risk since they do not exceed the
harm or discomfort of certain psychological examinations
or tests or those ordinarily encountered in daily
life.
Expedited Review
In order to qualify for expedited review, research
must be 1) both on the list of expedited review procedures
published in the Federal Register and be found by
the reviewer to be of minimal risk, or 2) involve
only minor changes in approved research. Expedited
review per se does not mean any decrease in human
subjects protection required in the conduct of the
research itself.
Timing of IRB Review in Relation
to Funding
Covered research may not be supported without certification
that the research has been reviewed and approved by
the IRB. The Common Rule itself does not actually
require IRB approval prior to agency review and/or
funding, but some Agencies may. In addition Sections
118 and 119 provide for activities funded without
definite plans for human subjects research. In any
case, IRB approval must precede the actual conduct
of the covered human subjects research.
Multiple Site Research
Section 114 addresses cooperative research. Each institution
is responsible for safeguarding subjects rights and
following appropriate procedures. However, institutions
may rely on the review of another qualified IRB. It
is recognized that the types of research, the levels
of risk and the kinds of sites where cooperative research
takes place vary widely and the need for considerable
adaptability is recognized. For example, the mere
fact that research occurs at a certain place (such
as a health department, school or supermarket) does
not mean that "place" would be considered
a research institution. If a site is only opening
its doors to researchers or data abstractors, or is
merely providing data, it is not considered a research
institution. While it is not necessary that every
site or every institution provide its own IRB review
(an IRB may be "remote" from the site of
the actual research,) it is important that the IRB
review and oversight that is conducted is explicitly
considered competent and cognizant of the conditions
and situations in the sites under its purview. One
specific mechanism is a cooperative amendment to assurances
of institutions participating in cooperative research,
which can be agreed to by those institutions, and
approved by the sponsoring agency to document the
terms of reliance on another institution's IRB.
Continuing Review
IRBs must conduct continuing review of covered research
at least annually. IRBs have considerable latitude
in what the review entails. The key concept is that
the review be substantive and meaningful. In some
cases it may involve a complete review of the entire
protocol by the full IRB together with any additional
changes, events and findings. It may also include
observations of the research or the consent process.
In other instances, IRBs may adopt more expeditious
procedures, for example relying on findings of a principal
reviewer or on research progress reports. The IRB
may consider a biomedical or other intervention study
closed when all active participation of the subjects
has ended and the investigator is no longer accessing
private identifiable information. Once a study is
closed, it is a good idea to have reasonable ongoing
procedures in place as appropriate and practicable,
to protect confidentiality and to provide feedback
of relevant emerging information to subjects.
Promoting Ethical Behavior in
Areas Exempt from the Common Rule
Even though certain classes of research are exempt
under the Common Rule, they should not be considered
exempt from common ethical standards. For example,
a certain survey may be exempt, but it is common courtesy
and otherwise generally reasonable to ask permission
and provide some simple information to respondents.
Likewise, research on existing specimens might not
record identifiers and thus be exempt, but researchers
ought still to take care to protect individual privacy.
The interest in promoting ethical behavior outside
the common rule is not intended as a mandate for more
structured procedures, but rather to advance a cultural
norm of ethical behavior for research and non-research
activities alike, to be exercised with discretion
by institutions and individuals.
Promoting More Active Oversight
of Higher Risk Research
As with any undertaking, a sense of priority is important
in dealing with human subjects research and institutions
are encouraged to exercise more active oversight beyond
the minimum requirement of the Common Rule for certain
higher risk research, as appropriate.
More active
oversight could include such activities as special
educational outreach to investigators and other appropriate
stake holders, site visits and observations of research
activities, research participant interviews as appropriate,
ongoing IRB briefings of research progress, timely
monitoring and evaluation of untoward events, and
data monitoring and safety boards.
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