University of Washington Human Subjects Manual
VII. Special Topics
- Investigational Drugs
All drugs intended for interstate commerce are regulated by the U.S. Food
and Drug Administration (FDA) Federal Food, Drug and Cosmetic Act. With few
exceptions, the research use of any drug or biologic substance that is
either not approved for marketing by the FDA or is not approved for the
research indication is prohibited without prior Human Subjects Review
Committee approval. The researcher is obligated to file an
"Investigational New Drug (IND)" application with the FDA. The
FDA will review the application and, if approved, will issue an IND
number.
The FDA regulations protecting human subjects in research are
substantially equivalent to 45 CFR Part 46. However, FDA regulations (21
CFR Parts 50 and 56) do not allow for a waiver of documentation of informed
consent when the principal risk of harm to the subject would result from
breach of confidentiality.. Likewise, the FDA regulations do not allow for
an alteration in or waiving of the required elements of informed
consent.
Human Subjects Review Committee review and approval is required for all
research uses of investigational drugs and biological substances. This
includes industry-sponsored protocols, investigator-initiated protocols,
protocols for off-label use of an approved drug or biologic, treatment uses
of unapproved drugs and biologics, as well as emergency uses of unapproved
products.
- Investigational Devices
Medical devices are regulated by the Federal Food, Drug and Cosmetic Act,
as amended by the Medical Device Amendments of 1976. In accordance with
this Act, the Food and Drug Administration (FDA) has established procedures
for obtaining an "Investigational Device Exemption" (IDE), which applies to
investigations conducted to determine the safety and effectiveness of
medical devices.
The IDE regulations distinguish between "significant risk (SR) devices"
and "non-significant risk (NSR) devices." Use of either kind of device in
research requires Human Subjects Review Committee approval and use of
informed consent.
Significant risk devices are those which present a potential for serious
risk to the health, safety, or welfare of subjects, and are subject to FDA
control and approval. To obtain FDA approval, the Human Subjects Review
Committee must first review and approve; then the sponsor, i.e., the person
or firm which initiates the investigation, submits an application for an IDE
to the FDA. Examples of significant risk devices are implants and
life-supporting equipment.
Non-significant risk devices include such items as crutches, elastic knee
braces, bed boards, bedpans, medical chairs, and tongue depressors. In
order to obtain approval to use a non-significant risk device for research
purposes, the investigator must present the Human Subjects Review Committee
with a brief explanation as to why the device is not a significant risk
device. If the Human Subjects Review Committee concurs with the
determination that a device involves a non-significant risk and approves the
research, the investigator is automatically considered to have an IDE
without submitting an application to the FDA.
The following categories of medical device investigations are exempted
from the IDE requirements but are subject to other FDA requirements;
- certain diagnostic devices without significant risk,
- testing of devices for reasons other than safety and effectiveness, without
placing subjects at risk,
- devices intended solely for veterinary use or for research on laboratory
animals,
- custom devices, and
- intraocular lenses.
In addition, two categories of devices have a temporary exemption
by FDA from IDE requirements;
- devices in commercial distribution before May 28, 1976
(except those formerly classified as new drugs or antibiotic drugs), and
- devices introduced on or after May 28, 1976, that the FDA has determined to be substantially equivalent to devices distributed before that date (except those formerly classified as new drugs of antibiotic drugs). "Substantial equivalence" is determined by FDA on the basis of a "Premarket Notification" (also known as a 510 [k] submission).
- Radiation exposure
Any activities involving procedures which expose subjects to a radiation hazard (e.g., a chest X-ray or a radioactive tracer), either during screening prior to a study or during the study itself, require the approval of the Radiation Safety Committee (RSC). This is true of radiation that results from standard clinical exposures, as long as they are performed for purposes of the study. In those cases where approval by the RSC has not been given prior to Human Subjects Review Committee review, Human Subjects Review Committee approval will be contingent upon RSC approval. Approvals from the Radiation Safety Committee are congruent in time with approval from the Human Subjects Review Committee. Therefore, renewal requests to the Radiation Safety Committee should be made at the same time as renewal requests to the Human Subjects Review Committee.
- Administration of Alcohol or Illegal Drugs
Investigators whose research requires the administration of alcohol or
illegal drugs to human subjects should take special care to screen out
inappropriate subjects, to provide information about the administration of
alcohol or illegal drugs to subjects in the informed consent statement, to
protect subjects against risks that may be entailed in experimentally
induced intoxication, and to protect subjects against post-experimental
risks.
- Screening subjects
Investigators should be very cautious about including members of
populations for whom alcohol or illegal drug use may be contraindicated.
In applying for human subjects approval, investigators should show
sensitivity to this issue and provide cogent justification for the inclusion
of members of high risk populations such as the following:
- Alcoholics or former drug users who are currently choosing to abstain
from alcohol or drug use;
- Persons who are currently in treatment for alcoholism, drug addiction,
problem drinking or drug use, or alcohol- or drug-related medical
problems (unless the administration of alcohol or drugs is an
integral component of the treatment of alcohol or drug abuse);
- Persons who have a history of past or present drug dependency
involving substances cross-tolerant with alcohol (e.g.,\
barbiturate abusers);
- Females who may be pregnant or who are pregnant. Such persons should not
be included in research that involves the administration of alcohol
or illegal drugs. If there is doubt concerning pregnancy, a
medical clearance for alcohol use should be obtained prior to
the participation of the subject;
- Persons who have a history of adverse reactions to the type of
alcoholic beverage or drug or the amount of alcohol or drug to be
used in the study;
- Persons who are presently taking medication that may interact with
alcohol or illegal drugs;
- Persons who are presently abusing other psychoactive substances; and
- Persons who have any type of neurological defect.
- Informed Consent
When alcohol or illegal drugs are administered the consent process should
include the following:
- Subjects should be informed of the type of alcohol or illegal drugs
to be administered and of the amount unless consumption is
ad lib;
- When a placebo or nonalcoholic beverage is administered to some subjects,
the subject should be informed that he/she might receive either an
alcoholic or nonalcoholic beverage or active or inactive drug as part of
the experimental procedure;
- When subjects receive alcohol or drugs, a cautionary statement about
post- experimental activities is required. An example is: "You should not
drive a car or use any dangerous equipment, or do any work which requires
muscle and mental coordination for at least four hours after the study."
The period of caution should be extended to be appropriate to the BAL
obtained or the half-life of the drug.
- Risks
- Due consideration should be given to individual variation in rates of
alcohol and drug absorption. In order to decrease individual variation in
the maximum blood levels attained by subjects, alcohol and drugs should be
administered in the post-absorptive state, that is, after a 4 to 10 hour
period without food or fluid.
- Blood alcohol level (BAL) or drug levels should be determined by
standard methods. Commonly used methods of measuring BALs
include breath analyzers, intoximeters, and gas chromatography.
- Persons who are given enough alcohol to produce a blood level of
0.05 gm% or above should be under continuing supervision. Should
a subject with a BAL of 0.05 gm % or above have to be left alone
in the laboratory, a signal by which the subject can immediately
communicate with the experimenter should be arranged.
- Persons with BALs below 0.05 gm % may be supervised at the discretion
of the investigator. In deciding on the need for supervision,
the investigator should consider such factors as the behavior
of the subject, the subject's report of any untoward reactions
to alcohol, and the subject's drinking and drug use history.
It is recommended that special precautions be taken with
subjects who are naive to the effects of alcohol or drugs
or who have a low tolerance for alcohol or drugs.
- Protection against post-experimental risks
- At the termination of the experiment, persons who have been
given enough alcohol to produce a blood level of 0.05 gm %
or above or who have been given illegal drugs should be given
the choice of one of the following:
- To be escorted by the experimenter or designated assistant to
the subject's place of residence; or
- To remain in the laboratory setting under supervision until
such time as the blood alcohol level falls below the 0.03 gm %
level (or lower if Federal guidelines are modified to so require).
- Subjects should be given written information concerning their blood
alcohol level at the end of an experiment. They should be reminded of
possible risks at that level and of potential problems if they proceed
to consume more alcohol or illegal drugs. They should be given an
estimate of the number of hours before they are likely to reach a blood
alcohol level of 0.0 gm
- If deception is a necessary part of research in which alcohol or illegal
drugs are administered, the nature of and the reason for the deception
should be explained to the subject following the experiment. If
appropriate, the debriefing should also be designed to relieve any anxiety
the subject may have about his or her performance in the experiment.
- Additional information
For additional information and assistance on the administration of alcohol and illegal drugs and the protection of subjects, contact Human Subjects Division, Office of Sponsored Programs (543-0098) or the Alcoholism and Drug Abuse Institute (543-0937).
- Research using records and stored biological specimens
Humans Subjects Review Committee approval must be obtained in most
cases in which research activities include the use of data from records or
stored specimens (blood, urine, tissue, and other human products). For
purposes of this discussion, health care information records (including
financial records, pharmacy records, x-rays, CT scans, MRI and other images
and recordings), diagnostic specimens, pathological specimens and residual
specimens are treated as health care information.
- Using health care records and information with written consent:
State law requires that explicit written consent is obtained from the
patient/subject before his or her records or materials (specimens, x-rays,
billing information, etc.) are used for research purpose. This law applies
to all researchers including health care professionals unless the
information is being used to provide direct patient care. The consent must
state the name of the person(s) who want to use the information, the purpose
for which the information is to be used, and must be dated. This release
may be included in a standard consent form as long as all the necessary
elements are included.
If the research otherwise qualifies as exempt (information to be used
must "exist" at the time the research proposal is formulated) from
University-level review by the Human Subjects Review Committee, and the
patient's explicit written consent is obtained for the use of health care
information, the research may be reviewed at the department level, using the
Certification of Exemption form. Departments would be well advised to
review the consent forms to make sure they include all the necessary
elements of consent.
- Using health care records and information without consent:
State law does allow a waiver of the requirement to obtain written
consent to use health care information, provided that the research has been
reviewed by the Human Subjects Review Committees and that a Confidentiality
Agreement has been negotiated between the investigators and the
Committees.
Although explicit written consent is always preferred, such a waiver
should be requested if it is truly not feasible or practicable to obtain
written consent for the use of health care information. The researcher must
complete a Human Subjects Review Committee application form so that the
Human Subjects Review Committee may determine that the benefits of the
research outweigh the risks posed by waiving the requirement for written
consent -- invasion of privacy and breach of confidentiality.
If the research activity consists solely of the use of health care
information, or if its other components also qualify, the application will
be reviewed as "minimal risk." A subcommittee of the Human Subjects Review
Committee will review the application and, if it is approved, will draft a
Confidentiality Agreement to be signed by the researchers and by the
authorized University official.
Confidentiality of records. There are several special laws concerning
access to records. The most important of these is a State of Washington law
enacted in 1985, which deals with research records, and Acts concerning
educational and medical records. Academic records are excluded from this
statute because their use is restricted by the Buckley Amendment to the
Federal Family Educational Rights and Privacy Act. Psychiatric records are
further protected by the State Involuntary Treatment Act.
For additional information on this legislation, investigators may consult
with the personnel of the Office of Sponsored Programs, Human
Subjects Division, or with the Attorney General's Division.
- Confidentiality
Confidentiality of the identity of subjects and of information from
subjects is an important part of any research activity. Especially in
behavioral research, but also in bio-medical research, breach of
confidentiality and invasion of privacy may pose the greatest risks of harm
associated with the research. Wherever possible, research data should be
retained without any identifiers. When this is not possible, as in the case
of longitudinal research or research which links data from several sets of
data, investigators must take steps to protect the confidentiality of the
subjects and the data.
Any unintentional but identifying data or information on data collection
forms, questionnaires, and other records usually should be removed,
stricken, or otherwise made indecipherable as soon as noted by the
investigator.
In those instances where it is necessary to identify respondents,
identification on data collection forms, questionnaires, and other records
should be by code, with the code translation to be kept separate from the
data. The code should not be an identifiable number such as a hospital's
patient number, a student identification number, or a Social Security
number; rather, a code should be established solely for the purpose of the
study. Both the code translation and the data should be kept in a secure
place, such as a locked file cabinet, accessible only to the investigator,
to his or her authorized staff, and to others identified in the Human
Subjects Review Committee application.
Where information will be computerized, no names or other identifying
information should be entered. The study code number should be the only
computerized identifier. The code translation should not be entered into
the computer.
Exceptions to this policy may be made when it is necessary for the
conduct of the study to collect and link data on the same individual from
more than one source. In such instances the procedures for maintaining
confidentiality of both the paper and computerized records should be clearly
described and justified in the Human Subjects Review Committee application
form.
Social Security numbers need to be collected from subjects who may
receive monetary inducements exceeding $50.00 during a calendar quarter.
The list of subjects, Social Security numbers, and payments should be kept
in a secure place separate from the data.
Because subject anonymity is an important part of exempt research, a brief
discussion of it is in order. The phrase "identifiers linked to the
subject" appears in the Federal regulations. This means any name, code, or
reference that could be used to identify the subject outside of the context
of the research setting. Names, student numbers, and Social Security
numbers are obvious examples of identifiers. An identifier that links a
subject to a list of names or identifiers kept elsewhere is also an
"identifier linked to the subject." For instance, numbering data records
and keeping a list of subject names and record numbers creates an identifier
linked to a subject, even if the list is well guarded. Similarly, if
records are linked to a second set of records (e.g., test scores linked to
school grades) and the second set of records is identified, then the first
set would also be identified. The key question is, "Is there any way that
anyone, including the investigator, could start with a data record and trace
it back to the person being studied?" If the answer is yes, then there is
an identifier linked to the subject.
Records may be numbered so that they can be associated with each other without creating an identifier linked to the subject. For example, if a study extends over several sessions, the data from one subject can be assigned a unique number without creating an identifier providing that there is no way that the record number can be associated with a person.
Investigators frequently have to know a participant's identity in order to schedule appointments and otherwise arrange for data collection. Ordinarily this sort of temporary identification does not create an identifier providing that the data collected cannot be traced back to an individual subject. In certain cases, however, the information that the subject participated in the research at all might be considered confidential and sensitive. For instance, this situation would occur if the study were of persons who have committed illegal acts. When the fact of participation is itself sensitive, any record identifying the subject is considered sensitive and confidential.
Investigators who collect sensitive information from subjects who may be identifiable as study participants may apply for a federal Certificate of Confidentiality. The Certificates are available to all investigators, whether or not their research is funded by the federal government, and regardless of the kind of sensitive information being collected. The Certificate is intended to protect identifiable research data from disclosure through subpoena, warrant, or court order. There are exceptions to the Certificate's coverage. For further information about Certificates, please contact the Human Subjects Division.
- Compensation for adverse events
The University's policy on compensation for adverse events to human subjects is intended primarily to provide necessary medical care to subjects who sustain bodily injury as a direct result of participation in a research project.
"Adverse Effect" is defined to mean bodily injury. Except in special
circumstances, the term does not include impairment of mental processes or
emotional distress, nor does it encompass effects resulting from: (1)
injuries from diagnostic or therapeutic procedures, either standard or
experimental, performed as part of patient management; (2) the normal
course of a disease or condition; or (3) non-compliance with study
procedures.
The program operates on a "no-fault" basis; that is, the claimant does
not need to establish negligence. Rather, the claimant or the
investigator must demonstrate only that the subject has suffered an
adverse effect as a result of participation in a University-sponsored
study. The program is included as part of the University's overall
general liability self-insurance program.
If an investigator believes an adverse effect has occurred, he or she
should immediately prepare a report summarizing the background, nature,
and result. A form for this purpose may be obtained by telephoning the
Human Subjects Division. The report will be submitted to the Human
Subjects Division and the Office of Risk Management, which may consult
with the Attorney General's Division and the Human Subjects Review
Committee in making a determination as to the applicability of the
compensation program.
A report must be submitted within one year of the occurrence of the adverse effect, but as soon as possible after the researcher becomes aware of the event. In a case of latent disability, the time for filing the report does not begin until the subject or the subject's legal representative is aware or reasonably should be aware of the causal relationship of the disability to his or her participation in the research. This allowance takes into account an adverse effect to a fetus.
The compensation program for adverse effects may not apply to research
carried out by investigators under grants administered through other
institutions; and it is not effective for research carried out in foreign
countries. However, adverse effects should be reported to the HSD whether
or not the investigator believes that the compensation plan may be
applicable.
It is the position of the University of Washington that subjects and their third party payers or governmental programs should not be held accountable for the costs of treating adverse effects incurred as a result of taking part in clinical trials sponsored by commercial companies.
The terms of the agreement under which the trial is conducted shall
determine whether the sponsor or the University of Washington is
financially responsible for the treatment of adverse effects. With rare
exception, the agreement will specify that the University will hold the
sponsor harmless from adverse effects resulting from the negligence of
University employees, including failure to adhere to the protocol, while
the sponsor will hold the University harmless from adverse effects
resulting from the prescribed use of the test article or protocol. It is
possible, though unusual, that both University negligence and sponsor
negligence could concurrently cause an adverse effect, in which both
parties
share financial responsibility.
The consent form should include information that physical injuries to
the subject that are a direct result of study procedures will be treated
at no cost to the subject. Wherever possible, the consent form should
state that the sponsor is the responsible party. For example:
"If you have a physical injury as a direct result of this study, we
will treat you or refer you for treatment. The X company, the sponsor of
this study, will pay for this treatment."
In cases in which the sponsor does not wish to be named, acceptable wording is as follows:
"If you have a physical injury as a direct result of this study, we will treat you or refer you for treatment. The treatment will be given at no cost to you."
In rare instances in which the University's compensation plan does not
apply, or when the sponsor has made no provision for treating adverse
events, the subject or the subject's health insurer may be the payer of last
resort. In this case, the consent process should include this information,
along with the proviso that insurers may not be willing to pay for treatment
of adverse events resulting from treatment provided in the research context.
The Human Subjects Review Committee may request a pre-approval procedure to
make sure that the insurer will pay for these costs before the subject is
enrolled in the study.
- Subject recruitment
To minimize coercion, investigators should stress the voluntary nature of
participation in diagnostic or therapeutic experimental procedures involving
patients, and should avoid, whenever possible, the use of their own
patients, clients, employees, and students in procedures which are neither
therapeutic nor diagnostic. In these latter situations, investigators
should solicit subjects through means such as bulletin board notices,
advertisements in newspapers, and announcements in classes other than their
own.
- Approaching Subjects to Participate
In order to avoid an invasion of privacy, it may be necessary for an
investigator to enlist the cooperation of other professionals and
organizations as intermediaries. This is appropriate when an investigator
has not had prior contact with prospective subjects and does not have access
to their names and addresses or telephone numbers from a publicly available
source. The intermediary does not obtain consent from the prospective
subject to participate in a research activity; rather the role of the
intermediary is to obtain consent from the prospective subject to release
his or her name and address or telephone number to the investigator. The
investigator then would make the contact regarding the study and obtain
consent. The intermediary who is willing to assist an investigator in this
way should not take a strong advocacy position in favor of a particular
research activity.
In some instances, the investigator may already have access to the
participant's name and other identifiers through a non-public source such as
a disease registry (e.g., an area-wide cancer registry) with which the
investigator is affiliated. Such sources should be used to identify
prospective subjects for study only if their own operations have been
reviewed and approved by the appropriate IRB. Subjects identified from such
sources may be contacted directly by investigators without the use of
intermediaries if they can be reasonably expected to know their names are
listed in the registry and that the registry will be used for research
purposes.
Voluntariness begins with recruitment. Potential subjects must not feel
that they have been coerced into participating, nor must they fear the loss
of some benefit to which they are otherwise entitled if they choose not to
participate. The researcher must stress the voluntary nature of research
participation to potential subjects when they are first approached. In many
cases this requirement is easily met. For instance, people who respond to a
recruiting notice placed in a newspaper or on a bulletin board are obviously
volunteers.
Special care must be taken if the person doing the recruiting (normally but
not necessarily the principal investigator) is a person who is in a
relationship of authority or service provision with respect to potential
participants. Such a situation can arise if a teacher recruits his or her
students, or if a health practitioner recruits patients as research
subjects. If possible, it is best to avoid such situations, but there can
be cases where this is not possible. It is the investigator's
responsibility to ensure that a person's decision to participate or not will
not have any effect on any other practitioner-client, employer-employee,
teacher-student or similar relationship. Furthermore, this must be clear to
the potential subjects. Human Subjects Review Committees will require
assurance that the voluntary nature of participation has been explained to
subjects in those situations where this is a consideration. When
appropriate, investigators should include in their application for approval
a discussion of how voluntariness is ensured.
There are situations in which a potential subject's privacy might be invaded simply by being identified as a qualified participant for a study.
Members of "support groups" for problems such as alcoholism, drug
dependency, or depression might justly feel their privacy had been invaded
if they were identified to an investigator. In such situations
investigators may ask persons who already have access to the necessary
records, groups, or other information to approach subjects for them. When
such a person serves as an intermediary for the investigator, that person
must also stress the voluntary nature of research participation. The
intermediary does not obtain consent from a prospective subject, the
intermediary obtains permission to release the potential subject's name to
the principal investigator, together with any other information that will
allow the investigator to contact the potential subject. The intermediary
may indicate his or her approval of the research, but should not take a
strong position advocating participation.
In some instances investigators may have access to a potential
participant's name and other identifiers through a non-public source, such
as a registry of persons suffering from a particular disease. Such sources
should be used to identify prospective participants in a study only if the
use of this source has already been reviewed and approved by an appropriate
Human Subjects Review Committee.
- Advertisements
Advertisements, flyers, public service announcements (PSAs), and other
forms of publicity may be used to inform potential subjects about a research
activity. The content of each such method used must be approved before use.
Text for advertising purposes must be straightforward and non-coercive. If
investigational drugs or devices are to be used, this information must be
included in the advertisement. The text should also include the name of the
University of Washington and a contact person as well as a telephone number
or address. National recruiting campaigns must be modified to include local
references and information.
Sites at which advertisements are to be posted may have their own
regulations about what can be displayed or printed. Approval from the Human
subjects Review Committee does not superseded these institutional
requirements.
- Grants and Contracts
All grants and contracts proposed by university faculty and staff must be
submitted through Office of Sponsored Programs using the GC-1 form. On this
form, the investigator is asked to provide information about the use of
human subjects. Proposals will not be forwarded from the university to the
proposed sponsor unless this information has been provided.
All federal agencies and many private sponsors require human subjects
approval before reviewing proposals for funding. Therefore, the
investigator must submit a Human Subjects Review Committee application so
that it is pending review at the time the proposal is transmitted from the
university to the sponsor. Most sponsors allow sixty days for review and
approval. Once approval has been received, the investigator should notify
the sponsor to that effect.
Center grants and program project grants typically involve more than one
project involving human subjects. Before the proposal can be transmitted
from the university, the investigator must document on the GC-1 that each of
the projects has received human subjects approval or is pending review.
Training grants require no accompanying human subjects approval. It is
the principle investigator's responsibility to assure that each of the
trainees obtains approval for his or her project, or works with a mentor who
already has human subjects approval for the project. the GC-1 accompanying
a training grant proposal should include a statement that each trainee will
obtain human subjects approval as soon as the research has been planned and
before human subjects are approached to participate.
For proposals to sponsors who do not require human subjects approval before review, a simple letter of intent on file with the Human Subjects Division is all that is required by Office of Sponsored Programs to transmit the proposal. The letter of intent should include the name of the principle investigator, the title of the proposal, the name of the agency to which the proposal is being submitted, the proposed dates of funding, and a statement that the investigator will submit a Human Subjects Review Committee application at least sixty days before approaching human subjects if the proposal is funded.
Grant and contract proposals which are substantially similar to existing activities with human subjects approval may be added to those approvals (see section III.G.3., above).
- Subject Compensation
Subjects may be compensated in a variety of ways for participating in
research activities. These include financial remuneration, merchandise
(gifts, toys, or vouchers), provision of services (parking fees, free meals,
medical treatment), and educational credit. The terms of all types of
compensation must be described in the consent form.
Compensation is intended to reimburse subjects for time and inconvenience, not for risk. The amount of compensation offered should not be such that it would be the sole motivation for a subject to participate in the research.
Compensation should be appropriate to the subject population. Adults may be offered, for example, a higher rate of compensation than children. The Human Subjects Review Committee will consider the compensation offered in the context of the subject population of the proposed study.
In most cases, compensation should be pro-rated for subjects who are not
able to complete the study. The schedule of payments should be outlined in
the consent form.
- Deception
In most investigations the subject should be made aware of the major purposes of the research. In some investigations, however, there is some degree of deception involved. Usually deception consists of merely failing to tell the subject what the specific points of interest are in an attempt to prevent biasing the results. Deception of this kind is reasonable and acceptable as long as the investigator provides justification for its use, and debriefs the subjects after their participation, when appropriate.
Problems arise when major deception is involved. For example, if an investigator leads a subject to believe that he or she has committed a crime, or has a disease, or has some serious character flaw, then the merit of the investigation must clearly counterbalance the risk to the subject for the research to be approved. Similarly, if an investigator studies some closed group such as a secret society by becoming a member without revealing his or her purposes, deception is being practiced through omission of information. Because this might put the group members at risk, the merit of the investigation must counterbalance the risk for such a procedure to be approved.
Withholding information cannot be used as a means to secure the participation of subjects in research.
The use of deception imposes special responsibilities on the investigator. One of these responsibilities is to provide appropriate debriefing to the subjects. In each case, the Human Subjects Review Committee will require information sufficient to understand why deception is needed, how the potential benefits justify its use, and how debriefing will be done.
- Electrical equipment
In order to assure the protection of human subjects in research involving electrical equipment to be performed under the auspices of the University of Washington, the Standards on Electrical Safety of the Joint Committee on Accreditation of Hospitals (see (4), below) and the Biomedical Electrical Safety Guidelines of the Department of Social and Health Services have been adopted. The following shall apply:
- All electrical or electronic equipment employed in research on human
subjects shall be in accord with the Biomedical Electrical Safety
Guidelines of the Washington State Department of Social and Health Services.
- When convenient, testing of such equipment shall be performed by hospital
personnel responsible for electrical safety, under the standards of the
Joint Committee on Accreditation of Hospitals. This responsibility is borne
by the Scientific Instrument Division at the University Hospital and by the
Medical Instrument Shop at Harborview Medical Center.
- Individual investigators, who for any reason cannot meet recommendation 2.,
above, shall submit a statement of their own regarding electrical safety,
following the pattern set forth in the Biomedical Electrical Safety
Guidelines. The statement shall indicate both the testing done to
assure safety of the original equipment and the plan for periodic
retesting.
- Standard on Electrical Safety of the Joint Commission on the Accreditation
of Hospitals (reprinted with permission of the Joint Commission on
Accreditation of Hospitals):
- DNA
Research involving recombinant DNA requires the approval of the Recombinant DNA Committee. In those cases involving human subjects where approval by that committee has not been given prior to Human Subjects Review Committee review, approval will be contingent upon Recombinant DNA Committee approval.
- Genetic research
Genetic information carries with it many possible risks, among them risks to insurability, risks to family life (for example, in incidentally generated information about paternity), and risks to life plans (for example, from discovery of previously unknown but possibly stigmatizing conditions). Investigators should provide the Human Subjects Review Committee with a full description of the kinds of testing which will be done, what kinds of data will be collected, how the data will be stored, and to whom they will be available (will they be entered in subjects' medical records?). The investigator should discuss the risks attendant on these procedures, and will be done to minimize them. These points should also be addressed in the consent forms under "Risks, Stress and Discomfort".
If genetic counseling will be available to subjects before and after testing, the investigator should explain who will do the counseling and describe the training and experience of the counselors.
If it is possible that the testing will provide evidence of previously undiagnosed or unrecognized illness, or susceptibility to illness, the investigator should describe how this
will be handled. Investigators should think in long-range terms about the potential risks posed by the research and how they will be handled.
- Research at or with Other Sites
- Cooperative Agreements
The UW currently has Cooperative Interinstitutional Review Agreements for
the Protection of Human Subjects with several local institutions. These
Agreements recognize each institution's approved Multiple Project Assurance
with the Department of Health and Human Services and generally provide for
only one review by a Human Subjects Review Committee (either the UW or at
the cooperating institution) on joint research projects. These Agreements
are subject to change through negotiation and interested investigators
should seek information on the current provisions of each Agreement from the
Office of Sponsored Programs, Human Subjects Division.
- Other Organizations
When agencies or institutions cooperate in UW research by providing
access to subjects, those organizations should be fully informed about the
research and official approval should be obtained before any subjects are
contacted. A copy of the letter(s) of cooperation should be submitted with
the application for human subjects approval.
For UW research conducted at non-UW sites not covered by an existing
interinstitutional agreement, duplicate review for the protection of human
subjects will be avoided when feasible in accord with the following
guidelines:
- If the research is carried out at an institution not having a
Multiple Project Assurance approved by DHHS, the research must be reviewed
and approved by the appropriate Human Subjects Review Committee at the UW
before the research is initiated.
- If the research is carried out both at the UW and at another institution,
the research must be reviewed and approved by the appropriate Human Subjects
Review Committee at the UW.
- Other Countries
In order to use subjects in societies or cultures outside the United
States, permission should be obtained from the host country (its government
or delegated agency). Complete information about the study should be made
available to the host government. Where written consent is appropriate, the
form should be translated into the native language. Although a formal
consent form may not be appropriate if contrary to national or local custom,
full disclosure to subjects of all information as specified in the Federal
regulations and by UW policy is required. A written statement containing
the content of this disclosure should accompany applications for human
subjects approval.
The university's compensation plan for adverse effects to human subjects
does not apply outside of the United States.
Investigators conducting research in foreign countries under a grant or
contract from a Federal agency should consult that agency concerning any
special requirements which may apply.
- DEFINITION OF TERMS
- Adverse Effect
-
An "adverse effect" is any physical, psychological or social outcome of an
investigation which is detrimental to a subject. Also referred to as
"adverse event," or "side effect."
- Anonymity
-
"Anonymity" means that no member of the research group knows the identity
of the subject, and that identification of subjects is not possible by
the procedures employed or by the information obtained from subjects.
- Assent
- "Assent" is a child's agreement to participate in research after an adequate explanation has been provided. Assent shall not be assumed simply because a child does not object. See Section IV for a discussion of when a child's assent must be obtained and the methods
for obtaining assent.
- Certification
- "Certification" is a report by the University that the appropriate review body has approved the use of human subjects in the proposed research. The DHHS and other funding agencies generally require such certification.
- Confidentiality
- "Confidentiality" is the restriction of information that identifies the subject, outside of the research group itself. See Section VII.F. for further information about confidentiality.
- Deception
- "Deception" occurs whenever information about a research activity is deliberately withheld from subjects. See Section VII.K. for a discussion of deception.
- Emergency Applications
- "Emergency Applications" are those which relate to situations where research procedures must begin immediately or the opportunity will be lost. See Section III.E. for further information.
- Incompetent
- In the context of the human subjects review process, an individual who is unqualified to give or is incapable of giving informed consent (see definition below) is considered to be "incompetent." An incompetent individual may be a minor, an adult who has been declared legally incompetent, or an adult whose competency may be questioned because of an illness or an unusual circumstance. See Section VI.D. for description of incompetent subjects.
- Informed Consent
- "Informed Consent" is the agreement of a subject to take part in research after the procedures, costs, and potential risks and benefits have been explained in a manner that the subject can understand.
- Institutional Review Board
- "Institutional Review Board" (IRB) is a committee which has been formally designated by an institution to review and approve research involving human subjects. It is also known as the Human Subjects Review Committee at the University of Washington.
- Intermediary
- An "intermediary" is an individual or organization that in another capacity has contact with prospective subjects, and that cooperates with an investigator to contact them. See Section VII.H. for a discussion on when and how an intermediary should be used to approach subjects.
- Minimal risk
- (see "risk")
- Minor
- A person under eighteen years of age is legally a minor, unless that person has been declared an "emancipated minor." Investigators who propose to use "emancipated minors" should check with the Human Subjects Division of the Office of Sponsored Programs about consent requirements, as the State of Washington does not have an inclusive definition.
- Modifications
- "Modifications" are changes in the research after a human subjects application has been approved. See Section III.G. for additional detail.
- Personal and Sensitive Information
- This term includes any information about an individual which, if known to unauthorized persons or the general public, might reasonably be expected to cause embarrassment or discomfort, jeopardize that person's prospects of employment or education, or affect his/her financial or social status.
- Prisoner
- "Prisoner" means any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing.
- Risk
- "Risk" is the potential for any physical, psychological or social outcome of an investigation that is detrimental to the subject (i.e. an adverse effect).
"Minimal risk" means that the risks of harm anticipated in the proposed research are not greater, considering probability and magnitude, than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests (from Title 45, Code of Federal Regulations, Part 46.102(g)).
Note: There are different types of adverse effects to which human subjects may be at risk that are inherent in various research procedures. Risk is most obvious in medical and behavioral science research projects involving procedures which may induce a potentially harmful altered physical state or condition. Some examples of such procedures are: the removal of organs or tissues for study, reference, transplantation, or banking; the administration of drugs or radiation; the use of indwelling catheters or electrodes; or the requirement of strenuous physical exercise.
There is a wide range of medical, social, and behavioral projects in which no risk of immediate adverse physical effects for the subject is involved (e.g. those involving the use of personality inventories, interviews, questionnaires, observations, photographs, tapes, records, and stored data). However, some of these procedures could involve a potential risk of discomfort, harassment, or a threat to the subject's dignity. Also, the information, if not kept confidential, could present psychological, social, or legal risks.
There are also medical and biomedical projects concerned solely with organs, tissues, body fluids, and other materials obtained in the course of routine performance of medical services such as diagnosis, treatment, and care, or of an autopsy. The use of these materials obviously involves no element of physical risk to the subject. However, their use for research, training and service purposes, if known to unauthorized persons or the general public, could present psychological, social or legal risks. In these situations, review may be necessary to determine whether the circumstances under which the materials will be procured are appropriate, and whether appropriate consent should be, or can be, obtained for the use of these materials for project purposes, and that the confidentiality of individuals will be maintained.
- Scientific Merit
- "Scientific Merit" is the contribution to science and society that a research project may make. In research involving no more than minimal risks, the Human Subjects Review Committee is not charged with judging the scientific merit of a proposed study. However, in research that involves more than minimal risk, the Human Subjects Review Committee must balance risks against their judgment of the scientific merit of the proposed study.
In cases in which there would be moderate or high risk and in which there are problems in determining scientific merit, the Human Subjects Review Committee may use consultants in making this determination. The Human Subjects Review Committee will not approve research when the risk is significant and the project is judged to lack adequate scientific merit.
- Subject
- A "subject" is a person whose physical, intellectual, emotional or behavioral characteristics are investigated for any purpose other than for the sole purpose of benefiting the subject as an individual. If a person, such as a family member, employer, or teacher, is asked to provide information about another individual, then both individuals are considered to be subjects. Donors of organs, tissues, and body fluids for research purposes and individuals whose records are used for research, are also considered to be subjects.
Special regulations apply to prisoners, residents of institutions for the mentally ill and the mentally retarded, as well as pregnant women, the viable fetus, the newborn, children, and the dead. See Part D.5. and Federal Regulations for a description of these regulations.
Note: This definition of "subject" excludes all accepted and established service relationships, such as the normal relationship of patients to physicians, students to professors, and other clients to professionals, in which the patient, student, or client is receiving aid or services intended only to meet his or her own personal needs. The professional-client relationship has the welfare of the client as the primary objective, whereas the investigator-subject relationship has the discovery of new knowledge as its primary objective.
The normal employee-employer relationship, in which legitimate services are exchanged for salary, wages, or remuneration in keeping with customary written or oral contracts, is also excluded from the definition of "subject." Payment of volunteers, however, does not alter their status as subjects. If doubt exists as to whether the procedures are within the normal limits of the employees' work scope, the employees should be considered to be participating as human subjects, and their rights and welfare must be protected.
- Subject Advocate
- A "subject advocate" is an individual who assists an adult subject who has not been declared legally incompetent, but whose ability to give informed consent is in question. The subject advocate should know the subject well enough to be able to attest to the subject's probable agreement to participate. The use of a subject advocate is discussed in Section IV.D.
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