Conduct of Human Studies
of Human Subjects Research | Designing
an Ethical Research Study | Informed
Consent | Selection
of Research Subjects | Privacy
and Confidentiality |Proper Conduct
of a Study | Monitoring
of Studies | Termination
of a Study | Emergency
Use of Investigational Drugs or Devices
research and some innovative diagnostic and therapeutic
activities that will involve human subjects whether directly
or indirectly must be reviewed and approved by the Human
Research Committee prior to their initiation. The Committee's
procedures and the requirements for review and action are contained in Partners Human
Research Committee Goverance and Operating Procedures.
This is available for investigators from the Partners
Human Research Office and should be consulted prior to
the preparation of protocols and consent forms for review.
our Multiple Project Assurances (MPAs), the Partners institutions
have made a commitment that all human research conducted
within the Partners HealthCare System or by a Partners
investigator will be performed in compliance with all
applicable local, state and federal regulations, the latter
being known as the "Common Rule" (Title 45 Code
of Federal Regulations Part 46).
conducting clinical research, an investigatorís actions
should be guided by the three fundamental ethical principles
for human research identified in the Belmont
Report: respect for persons, beneficence and justice.
Every investigator should read and understand the principles
set forth in the Belmont Report prior to participating
in any human research.
investigator and member of a research team should know
the following information about the responsible conduct
of clinical research before participating in any research
involving human subjects.
of Human-Subject Research
is defined as a systematic investigation, including
research development, testing and evaluation (i.e.,
pilot studies), designed to develop or contribute to
subject is defined as an individual about whom an
individual (whether professional or student) conducting
research obtains (1) data through intervention or interaction
with the individual, or (2) identifiable private information
includes both physical procedures by which data are
gathered (for example, venipuncture) and manipulations
of the subject or the subjectís environment that are
performed for research purposes.
includes communication or interpersonal contact between
investigator and subject.
information includes information about behavior
that occurs in a context in which an individual can
reasonably expect that no observation or recording
is taking place, and information which has been provided
for specific purposes by an individual and which the
individual can reasonably expect will not be made
public (for example, a medical record). Research
limited to the use of non-identifiable patient information
may qualify for exemption from HRC review; however
all exemptions must be granted by the Human Research
an Ethical Research Study
studies may be of direct benefit to the participants,
whether patients or volunteers, or the studies may be
of no direct benefit to the individual participants
but may ultimately be of help to others as well as contribute
to the advancement of scientific knowledge. One of the
most important components of such studies is that informed
consent be given by or for all participants.
human study should be well-designed according to sound
scientific principles and be preceded by adequate laboratory
and/or animal studies. A study which will not yield
valuable data is unacceptable.
study is ethical or not at its inception; it does not
become ethical because it succeeds in producing valuable
study should not be undertaken unless the risks and
hazards are believed to be predictable.
gain anticipated from a human experiment must be commensurate
with the risk involved. Risks and hazards to be evaluated
include the possibility of physical, psychological,
sociological, or other harm that might be incurred as
the consequence of a research activity. Sometimes large
risks are taken for large gains in human knowledge,
but in almost all cases such large risks should be taken
only when an individual is likely to benefit directly
in needed diagnosis or therapy. In all human research,
concern for the individual takes precedence over the
interests of science and society.
children under the age of 18 or others unable to give
consent for themselves are sought as subjects, there
should be essentially no identifiable risk associated
with participation in the study. If there is any risk,
it must be decisively outweighed by potential benefits
to the subjects.
should not take undue or unusual risk with themselves
in self-experimentation, but should exercise the same
prudence and judgment as they would in studies of others.
controlled clinical trial in diagnosis and therapy is
permissible under ordinary circumstances only when there
is uncertainty as to which of two procedures is better.
study design should minimize risk to the subjects and
maximize benefits. The use of placebo controls must
be scientifically based and ethically justifiable; in
such studies, special precautions must be taken to ensure
that no patient/subject will be denied effective therapy
when one is known to exist.
is preferable to have at least two professionally qualified
persons involved in experimental situations. Conflicts
of concern for the welfare of the patient and of interest
in the experimental study can arise when the personal
physician or the investigator attempts to encompass
both roles alone. Similarly, a controlled clinical trial,
in which experimental and control groups are compared,
is best supervised by two or more investigators rather
than by one investigator.
difficult ethical problems arise, it is often helpful
for them to be presented to a group of the investigator's
colleagues as well as to the Human Research Committee
for discussion and advice.
to beginning a human study, it is essential to obtain
the informed consent of the individual involved, whether
it be a patient or a healthy volunteer. Informed consent
is an expression of the willingness of a person to participate
as a subject in a research or experimental activity.
Such consent must be freely given, without coercion,
and must be based on a clear understanding of the nature
and purposes of the study and the factors involved in
participation. Firm application of the Golden Rule
would go far to eliminate difficulties here.
is the investigatorís responsibility to ensure that
proper informed consent is obtained from every subject
according to procedures approved by the Human Research
Committee; this responsibility cannot be delegated.
between subject and investigator should embody aspects
similar to those in a good patient-doctor relationship.
The discussion with the potential participant by the
investigator or co-investigator should include the purpose
of the research, the procedures to be followed, and
the discomforts, risks, and possible benefits, if any.
The signing of the consent document should signify that
thorough discussion has taken place and will continue
to take place during the conduct of the study.
being asked to participate in diagnostic or therapeutic
trials should be informed of any alternative choices
for diagnosis or treatment. All subjects should know
if their treatment is to be determined by random selection
and if placebos are to be used. No information should
be withheld that might influence the decision, nor should
there be promises of beneficial results.
patient or volunteer should feel at liberty to refuse
to join the study, or to discontinue participation at
any time, without prejudice to his/her present or future
same principles that pertain to obtaining informed consent
from patients and healthy volunteers should also be
applied by investigators in making a request for consent
from parents, next-of-kin or legally authorized representatives
of those unable to give consent for themselves due to
minor age, physical incapacity or mental incompetence.
In such cases a subject advocate may be appointed. When
a subject advocate is appointed, the subject advocate
is expected to act in the best interests of the subject
by sharing in discussions with the investigator and
with those responsible for giving consent.
minors are unable to give consent for themselves, children
of seven years or older should participate in the
consent process with the view of obtaining their assent
to join the study. If the study involves greater than
minimal risk or discomfort and does not offer the prospect
of direct benefit to the subject, the child must positively
affirm his/her willingness to participate.
individual's willingness to join a study must be documented
by a written consent form, or, in certain types of studies
as determined by the Human Research Committee, by oral
consent, noted in the subject's medical record. In rare
cases, the Human Research Committee may waive documentation
of informed consent when such documentation might constitute
a potential risk to the subject's privacy.
all cases particular care must be exercised to avoid
coercion to join a study, especially if the patient
or healthy volunteer is in a dependent relationship
to the investigator, or if monetary rewards are offered.
of Research Subjects
investigator should be aware of the medical history
of potential subjects and of previous studies in which
the individuals may have participated. While hospital
and physicians' records facilitate such screening of
patients, particular care should also be taken in discussions
with healthy volunteers to discover any information
that might preclude the subject's inclusion in the
study, such as past or present medical problems or participation
in other research studies.
studies of a captive group of subjects, such as students,
laboratory personnel, and hospitalized patients may
be useful and desirable and can be conducted in an ethical
fashion, a scrupulous effort must be made to preserve
the individual's rights because of the possibility of
of volunteers in the investigatorís own department or
who are the investigator's students should be avoided
and will usually be disapproved by the Human Research
Committee because of the subtle coercive factors that
could be present in even the most harmonious situations.
general, prisoners are not acceptable subjects for experimentation,
except when participation in research provides the only
prospect of receiving effective therapy for a given
medical condition. Under such circumstances, extreme
care must be taken to ensure that the interests of the
participants are protected and that all practicable
steps to eliminate coercion are taken. In such cases,
the likelihood that an individual will personally benefit
from participation in the research activity must be
compelling and outweigh the attendant risks.
conducting studies of patients in the Emergency Department
must observe the same ethical considerations required
in other areas of the hospital. If a patient in the
Emergency Department is unable to give consent, the
study must be of potential benefit to the patient and
consent must be obtained from the next-of-kin or legally
authorized representative before the patient is entered
into a study. Informed consent cannot be obtained retroactively
from a patient.
studies of the same individual, which are of no direct
benefit to that individual, should be avoided. Subjects
may unknowingly endanger their health by participation
in several studies in succession.
who are close to death or in danger of sudden death
are not suitable subjects for a study, unless the investigator
is convinced that the study will directly benefit the
individual and improve the quality of his/her remaining
life. Studies of such persons should not be made solely
for the benefit of science and society.
the course of a study, the highest standards should
be maintained with regard to the privacy and confidentiality
of information including interviews, photographs and
other records concerning the subject. Although more
investigators and staff may be involved in the conduct
of a study than might occur in the usual course of treatment
of a patient, confidentiality standards, as detailed
in the Partners Privacy and Confidentiality
Policies, should not be relaxed.
the records of certain studies must be made available
to the U.S. Department of Health and Human Services
or the U.S. Food and Drug Administration for audit purposes
and, sometimes, to a sponsoring drug company as a means
of validating results, confidentiality must still be
maintained and the identity of individuals disguised
as much as possible through the use of code numbers,
rather than names, medical records numbers, or other
commonly used identifiers, such as social security number.
patient's right to privacy becomes directly affected
in genetic and behavioral studies that require the participation
of a patient's relatives or friends. The patient should
be asked to obtain permission from relatives or friends
to be contacted by the investigator to participate in
the study. Parents or guardians of a child who is in
a study should be similarly consulted before a child's
siblings or playmates are approached for inclusion in
the publication and use of investigational results,
it must be made unmistakably clear that the all ethical
and privacy proprieties have been observed in the study.
One of these proprieties is adequate disguise of the
identity of the subject in text and photographs. Every
effort must be taken to protect the privacy and anonymity
of individuals in the report, as well as during the
of the uniquely personal and predictive nature of an
individual's genetic information, disclosure may have
serious psychological, social and economic consequences.
Great care must be taken to ensure that confidentiality
of genetic information is maintained and that the individualís
right to determine who has access to such information
is respected and preserved.
Conduct of a Study
Chief of Service/Department, as well as the investigator,
is responsible for assuring that the conduct of the
study follows the approved protocol, and that the investigator
abides by the decisions and procedures of the Human
Human Research Committee continually monitors ongoing
human research studies and is required to conduct a
complete and substantive review of every protocol at
least annually as part of its responsibilities for protecting
the rights and welfare of participants in the research
a study is suspended or cancelled due to adverse reactions
to a drug, procedure or mechanical device, the investigators
should also inform the participants in the study of
the reasons for the suspension or cancellation.
of a Study
study should be discontinued when hazards to the subject
are found to be greater than anticipated, or when one
treatment appears clearly to be less effective than
another with which it is being compared. Patients should
not be denied the benefits of the more effective treatment,
once its value has been established.
study should be deemed completed when a sufficient number
of patients or healthy volunteers have been studied
and valid information obtained.
Use of Investigational Drugs or Devices
FDA allows for the emergency use of an investigational
drug or device without prospective HRC approval when
the patient has a disease or condition that is life-threatening
or severely debilitating, the patientís disease or condition
requires intervention with the investigational drug
or device, and no alternative method of approved or
generally recognized therapy is available that provides
an equal or greater likelihood of saving the patientís
life, and time is not sufficient to obtain HRC approval.
consent must be obtained from the patient or the patientís
legally authorized representative unless the patient
is unable to communicate and time is not sufficient
to gain consent from the patientís legal representative.
institution is permitted ONE emergency use of an investigational
drug or device without prospective HRC approval. Under
FDA regulations, all additional uses of the investigational
drug or device should be anticipated and must be performed
under an HRC-approved protocol.
uses of an investigational drug or device must be reported
to the HRC immediately, followed by a full report within
5 working days.
other uses of investigational drugs or devices require
prospective review and approval of the HRC.