Cook County Health & Hospitals System
Office of Research & Regulatory Affairs
Hektoen Building - Room 333 - 627 South Wood Street
Chicago IL 60612
(312) 864-0716 or (312) 864-4821
RESEARCH WITH HUMAN PARTICIPANTS
GUIDANCE FOR RESEARCH INVESTIGATORS AND IRB MEMBERS
TABLE OF CONTENTS
INTRODUCTION – RESEARCH ETHICS WITHIN CCHHS
Page 2
HUMAN RESEARCH: ETHICAL FOUNDATIONS
Page 3
CCHHS INSTITUTIONAL REVIEW BOARD (IRB) REVIEW
Page 6
APPROVAL OF RESEARCH PROTOCOLS
Page 13
CENTRAL IRB GUIDELINES FOR REVIEW AND APPROVAL
Page 17
EXEMPTION FROM REVIEW
Page 19
USE OF INVESTIGATIONAL DRUGS OR DEVICES
Page 21
GENERAL REQUIREMENTS FOR INFORMED CONSENT & HIPAA AUTHORIZATION
Page 25
EXCEPTIONS FROM CONSENT REQUIREMENTS
Page 27
INFORMED CONSENT FOR SPECIAL PARTICIPANT CLASSES
Page 30
GUIDELINES FOR OBTAINING INFORMED CONSENT
Page 34
FORGOING PARENTAL CONSENT IN RESEARCH WITH MINORS
Page 38
RECRUITING RESEARCH PARTICIPANTS
Page 39
INCLUSION OF WOMEN AND PEOPLE OF COLOR IN RESEARCH
Page 42
INCLUSION OF CHILDREN IN RESEARCH
Page 44
MAINTAINING CONFIDENTIALITY – RESPECTING PRIVACY
Page 45
PREPARING THE RESEARCH PROTOCOL
Page 47
PREPARING THE APPLICATION
Page 48
RESPONSIBILITIES AFTER APPROVAL – INCLUDING DATA SECURITY
Page 50
PROGRESS REPORTS
Page 53
ADVERSE EVENT DETERMINATION AND REPORTING
Page 54
SCIENTIFIC QUALITY ASSURANCE PROGRAM
Page 57
FINANCIAL CONFLICT OF INTEREST
Page 61
APPENDIX
Regulatory Reference Links; Books/Websites
IRB Review Fee Structure (for Industry Sponsored Research)
Informed Consent Template and Sample Language
MS Word Readability Tools
Page 63
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INTRODUCTION - RESEARCH ETHICS WITHIN CCHHS
___________________________________________________________________
CCHHS is the main and historic public healthcare safety net for the County of Cook. While all
research at any health/human service institution is to be reviewed and monitored, CCHHS serves a
higher proportion of vulnerable populations of all types than most research conducting institutions;
thus a higher expectation exists for assuring protection of patients from undue harm.
A well-documented history of unfair and harmful research practice examples, especially with
vulnerable populations exists in the US and globally, right along with numerous examples of
population exclusion from beneficial research initiatives. In fact, among many vulnerable populations,
distrust of research and medical providers in general is not uncommon, due to real atrocities and
perceived notions of past practices.
Current Federal Rules and CCHHS IRB review and monitoring policies are designed to protect against
repeating both kinds of unacceptable practices.
This document is an effort to describe expectations and provide some operational guidance for the
ethical conduct of research done at all affiliates of the Cook County Health & Hospitals System including John H. Stroger, Jr. Hospital of Cook County, the Ruth M Rothstein CORE Center,
Provident Hospital, Oak Forest Health Center, the Cook County Department of Public Health, the
Ambulatory and Community Health Network, Cermak Health Services at Cook County Jail, and the
Cook County Juvenile Temporary Detention Center.
Such research includes all projects:



which will be carried out at an affiliate of the Cook County Health & Hospitals System (CCHHS);
or
which will be carried out by an employee of a CCHHS affiliate or Hektoen Institute acting as an
employee or agent of one of these institutions; or
which will recruit or enroll patients or employees of one or more of these institutions as research
subjects.
The first two parts of this document provides an orientation to policies governing ethical practice in all
research activities with human subjects for CCHHS research investigators, Institutional Review Board
(IRB) members, and explains the role of CCHHS Research & Regulatory Affairs Department staff.
The final part describes policies to prevent misconduct in science and financial conflict of interest in
research and an Appendix listing of reference materials and supporting information.
Please note that “subjects” is a term historically and traditionally used to describe the participation of
human beings in research studies. The term “participants” is more commonly used today, as an
updated term in place of the word “subjects,” in an effort to dispel notions of subordinate standing of
individuals participating in research studies from researchers who are conducting such studies. The
term “participants” will be used from this point forward, throughout this document, except in instances
of historical reference.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
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HUMAN RESEARCH: ETHICAL FOUNDATIONS
____________________________________________________________________
The history of modern biomedical science is marked by an ongoing tension between the necessity to
respect individual rights and the need to employ human participants for some types of medically
valuable research. The federal government, during the 1970s, set guidelines in the form of legislation
which applies to all institutions which receive federal research funds.
The principles underlying this legislation are contained in The Belmont Report, issued in 1978 by the
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.
The ongoing implementation of this legislation is carried out by a system of Institutional Review
Boards which must approve every research activity involving human participation at institutions
receiving federal research funds.
The Belmont Report (see Appendix for a link to the full report) found three quintessential requirements
for the ethical conduct of human research with human participants:
Respect for persons involves a recognition of the personal dignity and autonomy of individuals, and
special protection of those persons with diminished autonomy. This principle leads directly to the
requirement for informed consent. For consent to be informed, it must meet the standards of
information, comprehension, and voluntariness. Participants must be given sufficient information on
which to base their decisions, including information about the research procedures, purposes, risks and
anticipated benefits, alternative procedures, and a statement offering the subject the opportunity to ask
questions and to withdraw from the research at any time.
The information must be comprehensible, written in a format matched to the individual's capacity to
understand it. Most importantly, this means that medical jargon cannot be substituted for lay language,
that asking respectfully to see if the participant has understood the information may be necessary, and
that even persons of limited capacity be helped to understand their participation at the appropriate
level.
Voluntariness means that individuals must be well aware that they may refuse to participate, or may
cease to participate at their discretion at any time, without penalty or threat of penalty. Conditions of
consent must be free from coercion or undue influence.
Beneficence entails an obligation to protect persons from harm by maximizing anticipated benefits and
minimizing possible risks of harm. This implies that research investigators must conscientiously
conduct a risk/benefit assessment of the protocol or study design. From the viewpoint of the
participant, all risks -- physical, psychological, social or other -- must be kept to the minimum
possible. The risks that do exist must be balanced by clear benefits to the individual participant and/or
to the general social good. Participants must be thoroughly and completely informed of the risks
entailed.
The beneficence principle also implies that the protocol will be based on scientifically sound
reasoning. Neither risk nor inconvenience to subjects can be justified if the activity will not clearly
advance the state of scientific knowledge.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
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Justice requires that the benefits and burdens of research be distributed fairly. Selection of research
participants must be the result of fair procedures and result in fair selection outcomes. The "justness"
of participant selection relates not only to the person as an individual but also to the person as a
member of social, racial, sexual or ethnic groups. Researchers may not base selections on individual or
social favor or disdain. Participants may not be selected simply because they are readily available in
settings where research is conducted or because they are easy to manipulate as a result of their illness
or socioeconomic condition.
Social justice in research also implies an order of preference in the selection of classes of participants - adults are preferred over children, for instance -- and some classes of potential participants, such as
the institutionalized mentally infirm or prisoners, may be involved as participants only under certain
restrictive conditions.
Historical underrepresentation and exclusion of women, people of color, and in some cases children, in
various kinds of potentially beneficial research needs to be taken into account from a social justice
perspective, in the design of research protocols.
Distinguishing Clinical Care from Research
Federal regulations concerning human participant protection apply only to situations which clearly
entail research. Often the boundary between practice and research is blurred, so that treating a patient
with an experimental approach is difficult to differentiate from doing research on a participant. The
Belmont Report defines practice as "interventions that are designed solely to enhance the well-being of
an individual patient or client and that have a reasonable expectation of success. The purpose of
medical or behavioral practice is to provide diagnosis, preventive treatment, or therapy to particular
individuals."
Research, on the other hand, "designates an activity designed to test a hypothesis, permit conclusions
to be drawn, and thereby develop or contribute to generalizable knowledge... Research is usually
described in a formal protocol that sets forth an objective and a set of procedures designed to reach that
objective."
Reporting case studies is not research. The material is not collected systematically to come to a
generalizable conclusion, but rather, usually is come upon by chance and reports an unusual finding.
There is no hypothesis testing. Case studies do not fall under the purview of the CCHHS IRB.
Sometimes clinical practice can become research when it is prepared for dissemination as
generalizable knowledge. An example would be preparation of data from a quality assurance study for
publication or presentation outside the institution. In both cases the activity that produced the data is
not defined as research, and does not require prior IRB review, but does become "research" when
prepared for dissemination. Also in both cases, the research would likely qualify for an exemption
from review (see section below) as long as the data are not linked to individual identifiers.
Ethical Considerations in Collaborations
This Guidance describes in detail the procedures all investigators within CCHHS are expected to
follow to protect human participants in research. When carrying out collaborative research, an
investigator is also expected to be aware of the circumstances under which human participants are
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
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studied at collaborators' sites. For instance, if one was to collaborate on a study by analyzing
specimens obtained from patients at another institution, and if those specimens had been obtained
under misleading or coercive conditions, one’s own ethical responsibility would not be discharged by
having distance from the collection process or by the existence of human protection procedures within
CCHHS.
The responsibility of a CCHHS investigator is to find out under what conditions the specimens were
obtained, and to refrain from collaborating until there is an assurance that human participants are
protected at the collaborating institution. Most universities, academic medical centers and teaching
hospitals have procedures in place for protecting human participants -- as, for instance, an Institutional
Review Board and a Federal Wide Assurance (See Appendix).
However, most private practitioners, many community hospitals and many community clinics do not
have such procedures in place. If CCHHS investigator would like to collaborate with a person or
institution where such procedures are not in place, an assurance can be obtained for the project which
makes it clear for collaborating institutional partners to understand and be committed to the protection
of human participants in research. CCHHS investigators in this situation can contact the Office of
Research & Regulatory Affairs for help in obtaining such an assurance.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
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CCHHS INSTITUTIONAL REVIEW BOARD (IRB) OVERVIEW
____________________________________________________________________
Research involving human participants is governed by a uniform federal policy. Most federal agencies
subscribe to the uniform policy, including the Department of Health and Human Services (DHHS).
The CCHHS IRB reports to the DHHS Office of Human Research Protection (OHRP) by way of a
standing Federalwide Assurance (FWA 00001802), and therefore follows the standard federal
regulations guided by the ethical principles of the Belmont Report. The CCHHS IRB is officially
recognized by OHRP as the reviewer of research and clinical investigations regulated by the Food and
Drug Administration (FDA) (IORG0000119).
The FDA regulates most clinical trials of new drugs and devices, concurs with this standard policy, but
has not adopted it in its entirety. For this reason, some aspects of review and approval of protocols
involving human participants may have different requirements imposed by OHRP and FDA.
When both FDA and OHRP have jurisdiction, both sets of requirements must be met. Within CCHHS,
many research protocols do fall under both sets of requirements. Both the OHRP and FDA
requirements are incorporated into these guidelines.
All human research projects to be conducted at any CCHHS affiliate must be approved by the System
wide Institutional Review Board (CCHHS IRB) in accordance with the CCHHS Federal Wide
Assurance and Title 45 Part 46, Code of Federal Regulations. For research projects regulated by the
Food and Drug Administration (FDA), the CCHHS IRB also follows relevant FDA rules, including 21
CFR 50 and 21 CFR 56.
Research involving human participants may receive approval by the IRB. Research may require further
review and approval or disapproval by officials of the institution. CCHHS officials outside of the IRB
process may not override the lack of approval by the IRB. It is each researcher’s responsibility to
assure compliance with the requirements of the CCHHS FWA.
The following describes the oversight responsibilities of the CCHHS IRB for research:
CCHHS IRB
Cook County Health &
Hospitals System
Office of Research &
Regulatory Affairs
(Manages CCHHS IRB)
Located in:
Hektoen Building
627 S Wood Room 333
Chicago IL 60612
Oversees research at:
John H Stroger, Jr. Hospital of Cook County
Cermak Health Services - Cook County Jail and
Cook County Juvenile Temporary Detention
Center
Cook County Department of Public Health
Ambulatory & Community Health Network
(ACHN)
Oak Forest Health Center
The Ruth M Rothstein CORE Center
Provident Hospital of Cook County
Contacts:
Mildred Williamson, PhD, MSW Director
mwilliamson@cookcountyhhs.org,
312-864-0716
Betty Donoval, JD, MS Scientific Officer
bdonoval@cookcountyhhs.org,
312-864-4821
Audrey French, MD CCHHS IRB Chair
afrench@cookcountyhhs.org,
312-864-4578
Romina Kee, MD CCHHS IRB Vice Chair
312-864-3630 rkee@cookcountyhhs.org
Mission of the CCHHS Institutional Review Board:
To protect human participants involved in research conducted by or through the Cook County Health & Hospitals
System AND
To ensure research is conducted in accordance with ethical principles and all applicable laws and regulations.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
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Membership and structure of the IRB
Composition
IRB membership is comprised of scientists, nonscientists, and local community members (nonaffiliated). The committee strives for a balance of men and women, multiple professional specialties,
and the racial/ethnic diversity found in the communities served by CCHHS. The CCHHS IRB has at
least one “prisoner-representative” member who is an advocate for detained persons.
When the IRB receives protocol applications that require expertise beyond that available on the Board,
assistance is sought from qualified persons outside the Board membership. Outside experts serve in a
consultant role only.
Commitment
Board members are appointed for a 3 year renewable term by the Executive Medical Staff (EMS) of
John H. Stroger, Jr. Hospital of Cook County. The IRB meets twice monthly, to review protocol
applications.
Members are expected to attend all scheduled meetings. Phone or videoconference attendance may be
acceptable on occasion. If a member is unable to attend four consecutive regularly scheduled Board
meetings, or half of the meetings over a six month period, the Chair shall review the availability of the
member to serve on the Board.
Alternate Members
Alternate members appointed by the EMS with the same considerations as so-called “Permanent”
members and are encouraged to attend all meetings. The participation of alternate members is
welcome in all discussion and promotes the continuity of the Board’s review. If the total number of
members present exceed the number of regular or “permanent” members on the Board, the votes of the
alternate members are not counted or recorded (in reverse order of seniority). All members (permanent
and alternate) may provide expedited review for initial protocols and continuing review when such
review is relegated by the Chair.
Conflict of Interest
IRB members with conflicting interests related to a protocol under review may provide information to
the IRB, but may not participate or be present for discussion of approval and vote. Board members
are expected to identify the individual conflict of interest for the meeting record if appropriate.
Training
IRB members are given training materials including the self-guided tutorial, federal legislative
documents: 45 CFR 46, 21 CFR 50, 21 CFR 56, the Belmont Report, HIPAA guidance, along with all
CCHHS IRB forms and relevant policies. Periodic training sessions are held often for new and existing
members. A review checklist and Reviewer’s worksheet are provided with every primary reviewer
assignment. A member must attend at least three meetings prior to being primary reviewer for a
protocol. Members may attend meetings and conferences on the protection of human participants in
research.
Selection of the IRB Chair
The John H. Stroger, Jr. Hospital of Cook County Executive Medical Staff (EMS) in consultation with
the Director of the Office of Research and Regulatory Affairs selects and appoints the IRB Chair. The
Chair may be replaced at the will of the EMS.
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IRB Chair Responsibilities
a. Provides leadership in establishing and implementing IRB policy and procedure. As a
primary representative of IRB decisions, the IRB Chair has shared authority over all
IRB policy and procedures in collaboration with the institutional official and/or IRB
administrative director.
b. Maintain current educational activities reflective of the duties and roles of the IRB.
c. Represents the IRB in discussions with other segments of the organization including
researchers.
d. Together, with the Director of Research and Regulatory Affairs represents the
organization in discussions with federal authorities.
e. Review protocols and determine the level of review required based on risk assessment
for expedited or full review.
f. Serve as the primary reviewer for expedited and exempt protocols except when a
conflict of interest takes place (in which case the primary reviewer is the Vice Chair.).
g. Directs the proceedings and discussion of the meetings for focus on issues pertinent to
the IRB roles and responsibilities.
h. Is a voting member of the CCBHS IRB.
i. Review and make decisions concerning responses to conditions for IRB approval. The
Chair may delegate this activity to the IRB Administrative Staff.
j. Delegate expedited reviews to IRB members for review.
k. Review Requests for Modification and determine level of review required based on risk
determination.
l. Represents CCHHS on various research committees as a voting member or ex officio, as
appropriate.
IRB Member Responsibilities
a. Complete the CCHHS IRB educational program.
b. Participate in continuing education activities approved by the IRB.
c. Attend all scheduled IRB meetings when possible. (Because patient care is sometimes
unexpected and is the care-providers’ highest priority, CCHHS IRB attendance rules are
more flexible than some IRBs). Occasional teleconference/videoconference remote
participation in IRB meetings is accepted.
d. Maintain confidentiality of all protocols reviewed and discussed by the IRB.
e. Review all Full review protocols prior to the meeting.
f. Provide thoughtful discussion addressing the merits/deficiency of each protocol
application.
g. Remove his/herself from discussion and recuse him/herself from voting on protocols
which the member has a conflict of interest. (i.e. Principal or Co-investigator on the
protocol being reviewed)
h. Provide initial and continuing expedited review using the IRB checklist within 14 days
of request or notify the IRB office of available timeline.
i. If unable to attend a meeting, send written reviews for all assigned initial and
continuing review assignments.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
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Office of Research and Regulatory Affairs Responsibilities
a. The Director of the CCHHS Office of Research and Regulatory Affairs is the
designated Human Protections Administrator who has a direct reporting line to the
CCHHS Chief Executive Officer (the designated Institutional Official).
b. The Office of Research and Regulatory Affairs staff provides administrative support to
the Institutional Review Board, conducts educational programs and quality
monitoring/auditing of research activities conducted by CCHHS investigators for
compliance with federal regulations, state laws and CCHHS policies regarding research
ethics. All requests to conduct research involving human participants are submitted to
the IRB for review using the IRB Protocol application.
c. The IRB staff provides initial administrative review. IRB staff provides feedback to the
principal investigators to secure clarification if necessary.
d. The IRB Chair determines if IRB Protocol applications meet the criteria for exempt
status as defined in 45 CFR 46. Documentation of the exempt status is provided in the
file and identified in the approval letter sent to the principal investigator. The IRB will
be kept informed of IRB Protocol applications that have been found to be exempt from
IRB review in the monthly meetings and minutes.
e. IRB staff coordinates the review process of all IRB Protocol applications requiring
expedited or full review as determined by the IRB Chair or designee. The IRB will be
kept informed of IRB Protocol applications that have been approved under the
expedited review procedure in the monthly meetings and minutes.
f. The IRB staff is also responsible for logistical arrangements of meetings and recording
minutes of meetings. All current files of correspondence between the IRB and the
investigators, all IRB Protocol applications reviewed, progress reports, any reports of
injury, records of continuing review, and a listing of IRB members and qualifications
will be kept in the IRB office. These records will be maintained for a minimum of ten
years after the research protocol is closed.
g. IRB staff will contact the Principal Investigators (PIs) with protocols that are to be
reviewed by the full IRB with the time and place to attend if their presence is requested.
h. The IRB staff or the IRB chair will inform the PI, in writing, of the disposition of a
protocol reviewed at the IRB meeting in accordance with the written minutes of that
disposition.
i. The Office of Research and Regulatory Affairs reports on behalf of the IRB to
appropriate institutional officials, The Food and Drug Administration (when
appropriate), the Office of Human Research Protection (OHRP), and any sponsoring
agency of any injuries to human research participants or other unanticipated problems
involving risks to human research participants, any serious or continuing
noncompliance with the regulations or requirements of the IRB, and/or any suspensions
or termination of IRB approval for research. (Adverse Events or Unanticipated
problems to sponsors may be reported directly by the PI to the sponsor when
appropriate).
j. CCHHS IRB approved educational programs are administered by the Office of
Research and Regulatory Affairs.
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DESIGNATING A RESPONSIBLE INVESTIGATOR
Any fully-qualified professional employed by a CCHHS affiliate (including John H. Stroger, Jr.
Hospital of Cook County, Ruth M Rothstein CORE Center, Provident Hospital, Oak Forest Health
Center, Cermak Health Services, the Ambulatory & Community Health Network, the Cook County
Department of Public Health), or any person appointed to the medical or professional staff of a
CCHHS affiliate, may act as a Responsible Investigator for research.
The Principal Investigator (PI) for a project will also be the "Responsible Investigator" designated on
the Institutional Approval Forms. Residents, fellows and students may not be Responsible
Investigators, but may have their research sponsored by an attending physician or other fully-qualified
professional within CCHHS willing to act in that capacity. In this case, the attending physician is
designated the "Responsible Investigator". Likewise with other health professionals: a licensed social
worker employed by John H. Stroger, Jr. Hospital of Cook County, for instance, may be a Responsible
Investigator or may act as a Responsible Investigator on a social work student project, for example.
Any exceptions will require documentation from the Division Chief, Department Chair, or other
CCHHS affiliate leader as appropriate, indicating and verifying that the Principal Investigator of record
spends sufficient time at CCHHS and has sufficient knowledge of the administrative structure, to
assure true responsibility and accountability to the institution, and conduct the study in accordance
with CCHHS policies, state and local laws and federal regulations.
The PI must take responsibility and be accountable for the supervision and training of all persons
involved on any and all of their research projects, including volunteers or other research staff
members. A CCHHS Principal Investigator must:
a. Successfully complete the CCHHS-IRB approved educational program, prior to the
initiation of research, and assure that all personnel, including students or volunteers
involved with the research activity obtain CCHHS sponsored research ethics training as
well.
b. Submit IRB protocol application to the IRB Office for all research that uses living
human participants including surveys, questionnaires, medical records or human tissue.
c. Use current CCHHS forms and procedures described on forms for all submissions.
They are available on the intranet or by email request. Outdated forms will not be
accepted.
d. Accept accountability for the research team, inclusive of students and/or volunteers for
adherence to the principles of the CCHHS human participants’ protection program.
e. Attend the IRB meeting when the protocol submitted is to be reviewed by the full Board
if requested.
f. Provide clarification and modification as requested by the IRB staff on behalf of the
IRB.
g. Provide the IRB office with continuing review and closing reports as requested by the
IRB using current forms. A continuing review report is required 4-6 weeks prior to the
expiration of approval. Outdated forms will not be accepted.
h. Notify the Office of Research and Regulatory Affairs promptly, within 48 hours of any
injury to a human participant or unanticipated events related to the approved research
protocol. Adverse Events or Unanticipated problems to sponsors should be reported by
the PI to the sponsor as well.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
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i. Submit a Request for Modification for review to the IRB for changes in personnel,
objectives, informed consent or any procedures. Approval of the requested
modification must be secured from the IRB prior to the implementation of the
modification.
j. Notify IRB and study participants of new information including alternatives which
could influence willingness to participate in given research.
For projects that are parts of larger multi-institutional studies, we require that a qualified investigator
employed by a CCHHS affiliate be named "Responsible Investigator" to act as the locally responsible
party. This means that even if the overall project has a PI from another institution, the "Responsible
Investigator" as indicated on the approval forms will be one of our own employees or professional staff
members. All office communication goes through the Responsible Investigator.
The Responsible Investigator is expected to assure that all the expectations described in these
guidelines are understood and met by all study personnel, that all administrative approvals for the
research have been obtained, and that all required communications with the IRB are carried out. When
a research study will involve personnel from a number of disciplines, the Responsible Investigator will
involve appropriate staff members and administrators from those disciplines in the planning of the
study. In all cases, communication from the CCHHS IRB such as letters of approval for projects, or
notices that progress reports are due will be sent to the named Responsible Investigator. Thus the
Responsible Investigator must have sufficient knowledge of the project, its risks and any implications
for patient care, clinical functioning and administrative burden, to be answerable to the IRB and
CCHHS for the project. The burden of Responsible Investigator should not be taken on lightly.
All persons who are to be substantively involved in research with human participants must
successfully complete the CCHHS self-guided Tutorial, followed by attending an official training
session on research ethics, led by the Scientific Officer of the Office for Research & Regulatory
Affairs. To arrange a presentation for your department or group or to request the self-guided tutorial,
please do so by e-mail at bdonoval@cookcountyhhs.org, or call (312) 864-4821.
CCHHS Educational Program on Conduct of Research Involving Human Participants
a. All CCHHS researchers, staff, and students have access to the CCHHS IRB approved
educational program by email request.
b. In order to assure a baseline level of understanding of the fundamental ethical principles
governing the protection of the human participants in research, all those named in the
IRB Protocol application who have a substantive role in the research project will
complete the CCHHS IRB approved educational program.
c. All researchers are welcome to discuss the self-guided tutorial with Office of Research
and Regulatory Affairs staff.
d. The successful completion of the training is recorded and maintained in a database
managed by the Office of Research and Regulatory Affairs. Documentation of
completion of this formal education program is provided upon request. The individual is
expected to retain a copy of successful completion for his/her records.
e. Continuing education is the cornerstone of professional conduct and all investigators are
expected to stay current and encourage their staff, associates, and colleagues to keep
current with changing requirements and expectations.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
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f. The Office of Research and Regulatory Affairs will regularly post upcoming events and
continuing education opportunities including Research Ethics with Human Participants
when offered.
g. All CCHHS researchers and associated staff are required to obtain refresher/update
training every three years on CCHHS IRB policies, federal regulations or state laws
where applicable.
Fees for IRB Review
The CCHHS IRB charges a review fee for industry sponsored research. IRB review fees are not
charged for non-profit sponsored studies supported by the National Institutes of Health, other
governmental agencies, or investigator initiated studies. A one-time fee will be charged for the review
of any new industry sponsored research. There will be no charge for renewals,
amendments/modifications, unanticipated adverse events, or final reports.
The fees are based on the anticipated costs associated with the protocol review by the IRB and are
charged for services rendered. The fees are due in full even if the IRB does not approve the study,
participants are never enrolled, or the study is terminated before objectives are reached. IRB fees are
non-refundable and subject to change. See the Appendix for a current list of the IRB review fees
for exempt, expedited, and full board review studies.
The invoicing and collection of fees will be managed by The Hektoen Institute for Medical Research
with the assistance of CCHHS Office of Research & Regulatory Affairs. The IRB fee is to be
budgeted as a separate line item in the contract budget and reimbursed by the sponsor at the time of
contract execution. The study specific Hektoen fund number should be included in the IRB
submission.
When a new industry sponsored study is filed with CCHHS IRB, The Hektoen Institute will be notified
by Research & Regulatory Affairs that an invoice was sent to the Principal Investigator. Upon receipt
of the invoice, the Principal Investigator will direct The Hektoen Institute to transfer money from the
study’s fund to IRB account #129.
REPORTING CONCERNS ABOUT PROTECTIONS OF HUMAN PARTICIPANTS IN
RESEARCH
If you have a concern about the protection of human participants in research in any CCHHS facility,
contact the Office for Research & Regulatory Affairs at (312) 864-0716 or (312) 864-4821.
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APPROVAL OF RESEARCH PROTOCOLS
_________________________________________________________________
Any research involving human participants must be reviewed by the CCHHS Institutional Review
Board (IRB). Approval must be obtained before research activity can begin. Two levels of review are
possible: Full review and expedited review. In some cases, research may qualify for an exemption
from CCHHS IRB review, as described in this section.
Institutional officials may not approve a study which has been disapproved by the CCHHS IRB. On
occasion the Responsible Investigator may meet with the IRB to discuss any concerns or answer any
questions that arise during its review. Such a meeting may be requested by either the investigator or
the IRB.
For Approval of a protocol, the IRB requires the following:
(1) Risks to participants are minimized: (i) By using procedures which are consistent with sound
research design and which do not unnecessarily expose participants to risk, and (ii) whenever
appropriate, by using procedures already being performed on participants for diagnostic or treatment
purposes.
(2) Risks to participants are reasonable in relation to anticipated benefits, if any, to them, and the
importance of the knowledge that may be gained as a result of the study. In evaluating risks and
benefits, the IRB should consider only those risks and benefits that may result from the research (as
distinguished from risks and benefits of therapies that patients would receive even if not participating
in the research).
(3) Selection of participants is equitable. In making this assessment the IRB should take into account
the purposes of the research and the CCHHS site or setting where the research will be conducted and
should be particularly cognizant of the special problems of research involving vulnerable populations,
such as children, prisoners, pregnant women, physically, or mentally disabled persons, or economically
or educationally disadvantaged persons. Selection should necessarily reflect the CCHHS patient
constituency.
(4) Informed consent will be sought from each prospective participant or their legally authorized
representative, in accordance with and to the extent required by part 21 CFR 50 and 45 CFR 46.
(5) Informed consent will be appropriately documented, in accordance with and to the extent required
by 21 CFR 50.27 and 45 CFR 46.
(6) Where appropriate, the research plan makes adequate provision for monitoring the data collected to
ensure the safety of participants.
(7) Where appropriate, there are adequate provisions to protect the privacy of participants and to
maintain the confidentiality of data.
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(a) When some or all of the participants, such as children, prisoners, pregnant women, physically, or
mentally disabled persons, or economically or educationally disadvantaged persons, are likely to be
vulnerable to coercion or undue influence, additional safeguards have been included in the study to
protect the rights and welfare of these participants.
(b) In order to approve research in which some or all of the participants are children, the IRB must
determine that all research is in compliance with federal regulations. If the IRB is unable to approve a
research activity, it shall include written notification that states the reasons for the decision and give
the investigator an opportunity to respond in person or in writing. The IRB has the authority to suspend
or terminate previously approved research that is not being conducted in accordance with the
established requirements, or that has been associated with unexpected serious harm to research
participants. Any suspension must include a statement in writing of the reason for the IRB's action and
will be reported promptly to the investigator, appropriate CCHHS officials, the research sponsor(s),
and, in accordance with Federal regulations, and the Office of Human Research Protection.
FULL REVIEW
A Full Board Review is a review of proposed research at a convened meeting at which a majority of
the CCHHS IRB is present, including at least one member who is NOT a scientist. For the research to
be approved, it must receive the approval of the majority of members present at the meeting.
EXPEDITED REVIEW
An Expedited Review is a review of proposed research can be conducted by the CCHHS IRB chair or
a designated voting member, or group of voting members, rather than by the entire CCHHS IRB.
Federal rules permit expedited review for certain kinds of research involving no more than minimal
risk and for minor changes in approved research.
Minimal Risk Defined: A risk is minimal where the probability and magnitude of harm or discomfort
anticipated in the proposed research are not greater, in and of themselves, than those ordinarily
encountered in daily life of a person, or during the performance of routine physical or psychological
examinations or tests. For instance, the risk of drawing a small amount of blood from a healthy
individual for research purposes is no greater than the risk of doing so as part of a routine physical
examination.
The following list summarizes the ways in which research may be eligible for expedited review. When
applying for an expedited review, cite one or more of the nine criteria listed below which are
applicable to the proposed project.
Categories of Research That May Be Reviewed by the IRB through an Expedited Review1
Please note: The categories listed below should not be deemed to be of minimal risk simply because
they are included on this list. Inclusion on this list merely means that the activity is eligible for review
through the expedited review procedure when specific circumstances of the proposed research involve
no more than minimal risk to human participants.
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The Research must be minimal risk and fall into the following Research Categories:
(1)(a) Research on drugs for which an investigational new drug (IND) application (21 CFR Part 312) is
not required. (Note: Research on marketed drugs that significantly increases the risks or decreases the
acceptability of the risks associated with the use of the product is not eligible for expedited review.)
(1)(b) Research on medical devices for which (i) an investigational device exemption (IDE)
application (21 CFR Part 812) is not required; or (ii) the medical device is cleared/approved for
marketing and the medical device is being used in accordance with its cleared/approved labeling.
(2) Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:
(a) from healthy, nonpregnant adults who weigh at least 110 pounds. For these participants, the
amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur more
frequently than 2 times per week; or
(b) from other adults and children2, considering the age, weight, and health of the participants, the
collection procedure, the amount of blood to be collected, and the frequency with which it will be
collected . For these participants, the amount drawn may not exceed the lesser of 50 ml or 3 ml per kg
in an 8 week period and collection may not occur more frequently than 2 times per week.
(3) Prospective collection of biological specimens for research purposes by noninvasive means.
Examples: (a) hair and nail clippings in a non-disfiguring manner; (b) deciduous teeth at time of
exfoliation or if routine patient care indicates a need for extraction; (c) permanent teeth if routine
patient care indicates a need for extraction; (d) excreta and external secretions (including sweat);
______________________
1
An expedited review procedure consists of a review of research involving human subjects by the IRB chairperson or by
one or more experienced reviewers designated by the chairperson from among members of the IRB in accordance with the
requirements set forth in 45 CFR 46.110.
2
Children are defined in the HHS regulations as "persons who have not attained the legal age for consent to treatments or
procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted."
45 CFR 46.402(a). Source: 63 FR 60364-60367,
(e) uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gumbase
or wax or by applying a dilute citric solution to the tongue; (f) placenta removed at delivery; (g)
amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; (h) supra- and
sub gingival dental plaque and calculus, provided the collection procedure is not more invasive than
routine prophylactic scaling of the teeth and the process is accomplished in accordance with accepted
prophylactic techniques; (i) mucosal and skin cells collected by buccal scraping or swab, skin swab, or
mouth washings; (j) sputum collected after saline mist nebulization.
(4) Collection of data through noninvasive procedures (not involving general anesthesia or sedation)
routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. Where
medical devices are employed, they must be cleared/approved for marketing.
Examples: (a) physical sensors that are applied either to the surface of the body or at a distance and do
not involve input of significant amounts of energy into the subject or an invasion of the subject=s
privacy; (b) weighing or testing sensory acuity; (c) magnetic resonance imaging; (d)
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electrocardiography, electroencephalography, thermography, detection of naturally occurring
radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, doppler blood flow, and
echocardiography; (e) moderate exercise, muscular strength testing, body composition assessment, and
flexibility testing where appropriate given the age, weight, and health of the individual.
(5) Research involving materials (data, documents, records, or specimens) that have been collected, or
will be collected solely for non-research purposes (such as medical treatment or diagnosis). (NOTE:
Some research in this category may be exempt from the HHS regulations for the protection of human
subjects. 45 CFR 46.101(b)(4). This listing refers only to research that is not exempt.)
(6) Collection of data from voice, video, digital, or image recordings made for research purposes.
(7) Research on individual or group characteristics or behavior (including, but not limited to, research
on perception, cognition, motivation, identity, language, communication, cultural beliefs or practices,
and social behavior) or research employing survey, interview, oral history, focus group, program
evaluation, human factors evaluation, or quality assurance methodologies. (NOTE: Some research in
this category may be exempt from the HHS regulations for the protection of human subjects. 45 CFR
46.101(b)(2) and (b)(3). This listing refers only to research that is not exempt.
(8) Continuing review of research previously approved by the convened IRB as follows:
(a) where (i) the research is permanently closed to the enrollment of new participants; (ii) all
participants have completed all research-related interventions; and (iii) the research remains active
only for long-term follow-up of participants; OR
(b) where no participants have been enrolled and no additional risks have been identified; OR
(c) where the remaining research activities are limited to data analysis.
(9) Continuing review of research, not conducted under an investigational new drug application or
investigational device exemption where categories two (2) through eight (8) do not apply but the IRB
has determined and documented at a convened meeting that the research involves no greater
than minimal risk and no additional risks have been identified.
Central or Single IRB Approved Protocols: There are several, usually national, sometimes
international in scope, multi-site research studies that occur, all sharing the same hypothesis and
design, where CCHHS as an institution is one of many participating sites implementing the research.
Studies such as these have already been reviewed and approved by a Central or Single IRB overseeing
the ethics of the research activities, with written agreements in place with participating institutions, of
which CCHHS is one among them. This type of arrangement is not uncommon with many clinical
trials administered through the National Cancer Institute (NCI), for example. In some cases, CCHHS
may have one of its own IRB members to serve on the Central Institutional Review Board for multisite studies, where we have a collaborative agreement in place, such as those sponsored by the national
Patient Centered Outcomes Research Institute (PCORI). In each of these two examples, protocols
submitted to the CCHHS IRB are considered eligible for expedited review, due to their previously,
Central IRB-approved status when received by the Office of Research & Regulatory Affairs. CCHHS
IRB provides an expedited review and acknowledgement. The CCHHS IRB maintains the authority to
suggest protocol modifications, or opt-out of certain studies, based on a case-by-case review.
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CENTRAL IRB GUIDELINES FOR REVIEW, DOCUMENTATION AND APPROVAL
______________________________________________________________________________
When CCHHS has entered into an IRB Authorization agreement with a Central IRB, the following
steps should occur for Institutional approval:
Administrative verification responsibilities (CCHHS IRB Staff)
1. The protocol must be approved by the IRB of record*
2. The protocol is designated as an "expedited protocol" and entered as such into the CCHHS data
base.
3. The protocol will be numbered with a letter suffix to designate the IRB of record.
Examples: C for COG (Children’s Oncology Group); N for CIRB (National Cancer Institute
[NCI] Central Institutional Review Board [CIRB])
4. Additional verification to determine:
a. Principal Investigator (PI) is trained in research ethics and CCHHS guidelines;
b. There is no conflict of interest (COI);
c. Consent form (if required) has CCHHS current "local context language;"
d. CCHHS HIPAA authorization is included, (unless other HIPAA arrangements have been
approved by the CCHHS IRB; and
5. The CCHHS review date will be the approval date, and the expiration date will be synchronized
with the IRB of record.
IRB Member Reviewer responsibilities:
1. Review and determine if the protocol is appropriate to conduct with CCHHS patients. Much of
the consideration should occur at the Hospital Division/Department or CCHHS affiliate level.
Questions to consider would likely include, but not limited to:
a. Does this conflict with other priorities?
b. Are there are sufficient resources available?
2. The protocol should also reviewed from a CCHHS systemwide perspective, beginning with an
assessment of scientific merit and sufficient human protections;
a. Is this the right fit for CCHHS and CCHHS patients?
This may include circumstantial considerations such as:
b. Is there a place for patients to be between their AM and PM radiation appointments?
c. Are there other constituency/public health system considerations?
d. Is there anything in the protocol that is wrong, unacceptable or for which CCHHS has a
higher standard? For example: Will CCHHS enroll patients into phase I trials without
making it clear that this is NOT of benefit to the patient?
3. If there is an error in the protocol, the reviewer should identify it so the IRB of record may be
contacted.
4. Recommend accepting or refusing the protocol. If the reviewer wishes to allow the protocol
but has concerns he wishes noted, she or he may do this for the record. The CCHHS IRB
may or may not with to make these concerns known to the Central IRB. IRB members will
have an opportunity for questions, suggestions, and acknowledgement or decision to opt out (if
determined), followed up by CCHHS Office of Research & Regulatory Affairs administrative
review of non-substantive changes/updates/revisions going forward for the duration of the
study.
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Ongoing quality monitoring responsibilities:
1. Local deviations, if any occur, from a protocol should be reported to the CCHHS IRB. The
CCHHS IRB will advise on notification to the central IRB.
2. Local unanticipated problems involving risk should be reported to the CCHHS IRB. The
CCHHS IRB will advise on notification to the central IRB.
3. Local adverse events should be reported to the CCHHS IRB and to the Cooperative group
(for NCI protocols).
4. Amendments approved by the Central IRB should be forwarded to the CCHHS IRB (other
arrangements for notification may be made for NCI CIRB protocols, such as access to website).
5. Amendment is noted in CCHHS data base and new consent is submitted and noted if
appropriate.
6. CCHHS has no responsibility for continuing review, however, CCHHS IRB should
be kept aware of current expiration date**
**End date of CCHHS participation in protocol.
*PI must provide documentation.
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EXEMPTION FROM REVIEW
________________________________________________________________________________
In some limited cases, research may be exempted from CCHHS IRB review. Examples include
research which involves observation of adults in public places; record reviews and historical surveys
using preexisting data; and surveys, questionnaires and structured interviews involving adults in which
respondents' personal identifiers are not linked to their responses.
Note that an investigator may not make the final decision that his/her research is exempt without
confirmation of this status from the appropriate CCHHS IRB Chair or designee.
Please note that even when a project is exempt from ethical review, the IRB requires that
persons substantively involved in the research complete the self-guided tutorial for ethics in
conducting research with human participants. In addition, the IRB may require that the consent
form or process be approved. Once approved, the consent, like the protocol itself, has no
expiration date and need not be resubmitted unless the project is changed in some way.
The following excerpt from federal regulations (45 CFR Part 46) details the criteria by which a project
may qualify for exemption from review:
CRITERIA FOR EXEMPTION FROM REVIEW
1.
Research conducted in established or commonly accepted educational setting, involving normal
educational practices, such as (i) research on regular and special education instructional strategies, or
(ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or
classroom management methods.
2.
Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement),
survey procedures, interview procedures or observation of public behavior, unless:(i) information
obtained is recorded in such a manner that human subjects can be identified, directly or through
identifiers linked to the subjects; and (ii) any disclosure of the human subjects' responses outside the
research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the
subjects' financial standing, employability, or reputation.
3.
Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement),
survey procedures, interview procedures, or observation public behavior that is not exempt under
paragraph (b)(2) of this section, if: (i) the human subjects are elected or appointed public officials or
candidates for public office; or (ii) Federal statute(s) require(s) without exception that the confidentiality
of the personally identifiable information will be maintained throughout the research and thereafter.
4.
Research involving the collection or study of existing data, documents, records, pathological
specimens, or diagnostic specimens, 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 linked to the subjects.
5.
Research and demonstration projects which are conducted by or subject to the approval of
Department or Agency heads, and which are designed to study, evaluate, or otherwise examine: (i)
Public benefit or service programs;(ii) procedures for obtaining benefits or services under those
programs;(iii) possible changes in or alternatives to those programs or procedures; or (iv) possible
changes in methods or levels of payment for benefits or services under those programs.
6.
Taste and food quality evaluation and consumer acceptance studies, (i) if wholesome foods
without additives are consumed or (ii) if a food is consumed that contains a food ingredient at or
environmental contaminant at or below the level found to be safe, by the Food and Drug Administration
or approved by the Environmental Protection Agency or the Food Safety and Inspection service of the
U.S. Department of Agriculture.
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Most research conducted at CCHHS affiliates that is eligible for exemption falls in Category 2
(interviews, surveys, educational testing) or Category 4 (for retrospective compilation of existing data - note that "Retrospective" means that the data already exists at the inception of the study). Under
Category 4, information may not be linked directly or indirectly to personal identifiers such as subjects'
names or medical record numbers. Under Category 4, such identifiers must be removed at the time the
data is compiled. Category 4 also includes data prepared for publication from quality assurance
activities which, after completion, seem to merit general dissemination outside the institution.
Under Category 2, such linkage is not allowed only in cases in which such linkage could pose some
risk to the subjects (e.g., questions concerning illegal behavior).
If a research project seems to fall into one of the exempt categories, the research investigator must
receive confirmation of the project's exempt status from the Chair of the CCHHS IRB.
Pilot Studies
Pilot studies that have interventions or collection of data from living human participants are also
subject to IRB review for human participant protections. The principal investigator is required to
submit an IRB Protocol application for review. IRB approval must be secured prior to the study’s
beginning. Feasibility studies however, may be initiated to determine whether the logistics of a study
will work. In this case, no research data are being collected, there is no generalizable conclusion.
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USE OF INVESTIGATIONAL DRUGS OR DEVICES OUTSIDE
CONTROLLED CLINICAL TRIALS
___________________________________________________________________
All use, for clinical or research purposes, of investigational new drugs or devices at CCHHS affiliate
sites requires IRB approval and informed consent. In some limited circumstances, emergency use of
investigational new drugs may be made without prior IRB review (see below).
As described in a following section, treatment use of FDA-approved drugs for indications other than
those approved ("off-label use") may in some cases also require approval by the Chair or Co-Chair of
the IRB, but not prior IRB review.
EMERGENCY USE WITHOUT PRIOR IRB APPROVAL
The Food and Drug Administration recognizes that treatment decisions may be made outside of
research considerations. Physicians retain the authority to provide emergency medical care to their
patients without prior CCHHS IRB approval. In these cases, physicians must meet FDA requirements
to use investigational articles for emergency purposes.
An Emergency Investigational New Drug (IND) Request allows the use of an investigational article
outside an approved clinical protocol and without prior CCHHS IRB approval in emergency situations.
These are defined as:



life-threatening situations;
in which no standard acceptable treatment is available and,
there is not sufficient time to obtain prospective CCHHS IRB approval for use.
In all but the most acute life-threatening situations, the investigator is required to obtain prior verbal
approval of the Chair or Co-Chair of the CCHHS IRB. Patients offered investigational drugs on an
emergency basis must give informed consent. Limited exceptions to the consent requirement are
described below.
For the purposes of using investigational drugs for emergency treatment, the term "life threatening"
includes conditions that are either life threatening or severely debilitating:
Life threatening means diseases or conditions where the likelihood of death is high unless the
course of the disease is interrupted and diseases or conditions with potentially fatal outcomes,
where the end point of clinical trial analysis is survival. The criteria for life threatening do not
require the condition to be immediately life-threatening or to immediately result in death.
Rather, the patient must be in a life-threatening situation requiring intervention before such
intervention can be reviewed at a convened meeting of the IRB.
Severely debilitating means diseases or conditions that cause major irreversible morbidity.
Examples of severely debilitating conditions include blindness, loss of arm, leg hand or foot,
loss of hearing, paralysis or stroke.
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This exception to prior IRB review may not be used unless all of the conditions described above exist.
It allows for one emergency use of a test article. Any subsequent use of the investigational product
must have prospective IRB review and approval. The FDA acknowledges, however, that it would be
inappropriate to deny emergency treatment to a second individual if the only obstacle is that the IRB
has not had sufficient time to convene a meeting to review the issue. On the other hand, if there is a
clinical reason to believe that an investigational drug will be appropriate for emergency treatment of
multiple patients, a research protocol should be developed for its use and submitted for IRB review and
approval.
Within 5 days of the emergency drug use, the physician must make a report in writing to the IRB for
review and consideration at its next convened meeting. This report should detail:
1) the rationale for using the investigational item, including any evidence from prior studies that the
agent might be safe and effective for the condition being treated;
2) the clinical context for its use, especially addressing the threat to the patient and the lack or
ineffectiveness of approved alternative treatments;
3) if available, the FDA IND number for this agent and a copy of any ongoing protocol for its use.
Approval of the emergency drug request is not complete until given by the full IRB.
** Please note that patients treated under an Emergency IND Request may not be entered as
participants in a research project or clinical trial **
Obtaining an Emergency IND
The emergency use of an unapproved investigational drug or biologic agent also requires IND status
from the FDA. If the patient does not meet the criteria of an existing study protocol, or if an approved
study protocol does not exist, the usual procedure is to contact the manufacturer and determine if the
drug or biologic agent can be made available for the emergency use under the company's IND.
The need for an investigational drug or biologic agent may arise in an emergency situation that does
not allow time for submission of an IND. In such a case, FDA may authorize shipment of the test
article in advance of the IND submission.
OFF-LABEL USE OF APPROVED DRUGS
Within CCHHS clinical settings, when a medical provider prescribes an approved drug for treatment
for unlisted indications, IRB approval usually will not be required. A physician or other medical
provider with a permanent Illinois license may prescribe any approved, marketed drug to treat a patient
for an unlisted indication, provided he/she writes a valid order or prescription. If the administration is
coupled with data collection, and a plan to offer these data to gain approval for a new dose, indication
or administration, the use IS considered research and all human participant research procedures should
be followed.
Off-Label Research with Approved Drugs
Use of approved drugs in planned clinical trials is subject to the usual IRB review process. In addition,
there are circumstances in which FDA oversight may also be required, especially if the principal intent
of the study is to develop information about the product's safety or efficacy.
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FDA oversight is not necessary if the study meets all six of the following conditions:
1. It is not intended to be reported to FDA in support of a new indication for use or to support any
other significant change in the labeling for the drug;
2. It is not intended to support a significant change in the advertising for the product;
3. It does not involve a route of administration or dosage level, use in a subject population, or other
factor that significantly increases the risks (or decreases the acceptability of the risks) associated
with the use of the product;
4. It is conducted in compliance with the requirements of IRB review and informed consent;
5. It is conducted in compliance with the requirements concerning the promotion and sale of drugs;
6. It is not emergency research for which waiver of informed consent will be sought.
TREATMENT USES OF INVESTIGATIONAL DRUGS REQUIRING PRIOR IRB
APPROVAL
Investigational products are sometimes used for treatment of serious or life-threatening conditions
either for a single participant or for a group of participants. The following mechanisms expand access
to promising therapeutic agents without compromising the protection afforded to human subjects or the
thoroughness and scientific integrity of product development and marketing approval.
Open Label Protocol or Open Protocol IND
These are usually uncontrolled studies, carried out to obtain additional safety data (Phase 3 studies).
They are typically used when the controlled trial has ended and treatment is continued so that the study
participants and the control participants may continue to receive the benefits of the investigational drug
until marketing approval is obtained. These studies require prospective Institutional Review Board
review and informed consent.
Treatment IND
With a Treatment IND you may treat eligible participants with investigational drugs for serious and
life-threatening illnesses for which there are no satisfactory alternative treatments. A treatment IND
may be granted after sufficient data have been collected to show that the drug may be effective and
does not have unreasonable risks. Because data related to safety and side effects are collected,
treatment INDs also serve to expand the body of knowledge about the drug.
There are four requirements that must be met before a treatment IND can be issued:
1)
the drug is intended to treat a serious or immediately life-threatening disease;
2)
there is no satisfactory alternative treatment available;
3)
the drug is already under investigation, or trials have been completed; and
4)
the trial sponsor is actively pursuing marketing approval.
It is the responsibility of the drug manufacturer or the Responsible Investigator to obtain Treatment
IND status from the FDA before applying to the IRB for approval of the protocol. In addition to
prospective IRB approval, treatment IND studies require that patients give informed consent.
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Group C Treatment IND
The "Group C" treatment IND was established by agreement between FDA and the National Cancer
Institute (NCI). The Group C program is a means for the compassionate distribution of investigational
agents to oncologists for the treatment of cancer under protocols outside the controlled clinical trial.
Group C drugs are generally Phase 3 study drugs that have shown evidence of relative and
reproducible efficacy in a specific tumor type. They can generally be administered by properly trained
physicians without the need for specialized supportive care facilities. Group C drugs are distributed
only by the National Institutes of Health under NCI protocols. Although treatment is the primary
objective and patients treated under Group C guidelines are not part of a clinical trial, safety and
effectiveness data are collected. Although the FDA does not require local IRB review of Group C
protocols, the CCHHS IRB requires prior review and approval, as well as informed consent by the
patient.
FDA-regulated medical device research, making and documenting the significant/nonsignificant
risk (SR/NSR) determination:
CCHHS Research Investigators are to notate study sponsor assessment of SR/NSR status in their initial
submission application for review. The CCHHS IRB member serving as the primary reviewer will
make an assessment of concurrence or not with the study sponsor and include their determination in
their presentation. CCHHS IRB members are provided the FDA guidelines for making this
determination as follows: 21 CFR 812.3(m), defines a significant risk investigational medical device
(SR).
A significant risk device presents a potential for serious risk to the health, safety or welfare of a
research participant. Significant risk devices may include implants, devices that support or sustain
human life, and devices that are substantially important in diagnosing, curing, mitigating or treating
disease or in preventing impairment to human health. Examples include sutures, cardiac pacemakers,
hydrocephalus shunts, and orthopedic implants.
A SR device study must follow all the IDE regulations at 21 CFR 812 and cannot proceed until an IDE
application is approved by the FDA.
A nonsignificant risk (NSR) investigational medical device is one that does not meet the definition
for an SR investigational medical device. Examples include most daily wear contact lenses and lens
solutions, ultrasonic dental sealers and Foley catheters.
A NSR device study does not need to submit an IDE application to the FDA and can proceed with IRB
approval. The determination that a device is a SR or NSR is initially made by the sponsor. The
proposed study is then submitted to the FDA (for SR studies) or IRB (for NSR studies).
Criteria for IRB approval: In order to approve research in accordance with FDA and OHRP’s policy
the IRB shall determine that requirements are met as described above. Approval is determined
by a majority of the quorum. Members who have a conflict of interest may not vote. No proxy
votes are accepted. Documentation of the determination is placed in minutes of meetings and in
correspondence prepared to communicate IRB decisions back to investigators.
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GENERAL REQUIREMENTS FOR INFORMED CONSENT/HIPAA
___________________________________________________________________
This outline provides a summary of all the issues that must be addressed in the informed consent
process.
Legally effective informed consent shall:
Be obtained from the participant or the participant's legally authorized representative;
Be in language understandable to the participant or representative;
Be obtained under circumstances that provide the participant with an opportunity to consider
whether or not to participate, and that minimize coercive influences;
Not include language through which the participant is made to waive any of his legal rights or
which releases the investigator, sponsor or institution from liability for negligence.
BASIC ELEMENTS OF INFORMED CONSENT
The following can be used as a checklist to insure that your consent procedure is complete.
A basic consent includes:
1. A statement that the study involves research;
an explanation of the purposes of the research;
the expected duration of the person's participation;
a description of procedures to be followed;
identification of any procedures which are experimental.
2. A description of the expected risks or discomforts to the participant.
3. A description of benefits to the participant or to others.
4. A disclosure of alternative procedures, if appropriate.
5. A description of the extent to which confidentiality will be maintained.
For FDA-regulated research, a statement that the FDA may inspect the records.
6. For research involving more than minimal risk, an explanation as to whether
compensation and medical treatments are available if injury occurs.
7. An explanation of whom to contact if questions arise about the research, the
participants' rights, or whom to contact if a research-related injury occurs.
8. A statement that participation is voluntary, that refusal to participate involves no
penalty or loss of benefits, and that the subject may discontinue at any time.
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ADDITIONAL CONSENT REQUIREMENTS When required by the IRB, one or more of
the following additional elements are provided to each participant:
1. A statement that a procedure may involve unforeseeable risks.
2. A description of circumstances under which the participant's participation may be
terminated by the investigator without the participant's consent.
3. Additional costs to the person resulting from participation in the research.
4. The consequences of the participant's decision to withdraw from the research.
5. A statement that significant new findings developed during the research which may
relate to the person's willingness to continue will be provided to participant.
6. The approximate number of participants involved in the study.
The Office of Research and Regulatory Affairs has prepared a consent template with sample language
that is often useful. This sample template may be found in the Appendix.
HIPAA Authorization
The Health Insurance Portability and Accountability Act of 1996 provided supplemental protection of
privacy provisions through the privacy rule often referred to as “HIPAA.” These provisions protect the
release of Protected Health Information (PHI) in “covered entities.” CCHHS is a covered entity.
Although the act is extensive and concerns elevator conversation and electronic records, it important to
know that because PHI is collected for research purposes, the research investigator must obtain a
HIPAA authorization for all research participants unless the law permits for a waiver of authorization.
PHI is any combination of health information (even if provided by the person him or herself) together
with an identifier such as name, social security number, medical record number, or any combination of
month, day and year. HIPAA elements must be covered in a separate HIPAA authorization form
provided by the IRB office.
Use of health data for clinical care, billing and normal operations such as quality assurance do not
require a separate HIPAA authorization.
If a Waiver of consent of documentation of consent is requested, it is likely that a waiver of HIPAA
authorization is also appropriate. Transmission of PHI must follow HIPAA security precautions.
PHI should not be included in the body of an e-mail – instead, use an attachment. The attachment
(Word document, Excel workbook, PDF) must be Encrypted and Password Protected; the sender may
use versions of Word 2007 or later, Excel 2007 or later or, a PDF creator that supports encryption and
passwords. The sender MUST send the document in one e-mail and the password in a DIFFERENT email. Do not send the password and the encrypted attachment in the same e-mail.
Please consult “E-Mailing Protected Health Information” on the CCHHS Intranet site under the
“Compliance” tab as well as the IRB Intranet forms for additional information.
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EXCEPTIONS FROM CONSENT REQUIREMENTS
____________________________________________________________________
Exemption from review versus waiver of consent
Investigators sometimes confuse the status of "exempt from review" and "waiver of informed consent".
These are actually two separate concepts. A project that is exempt from review has such minimal risk
that it does not require ongoing IRB oversight, but the rights of research participants do not change just
because the project carries minimal risk.
For example, a survey of patient attitudes about some aspect of their care may very well be exempt
from IRB review. It would be completely unacceptable, however, for the interviewer to imply to the
participant that he/she had to answer specific questions, or that there would be a penalty for refusing to
participate. In fact, the IRB often requires a brief statement at the start of an interview or survey that
the respondent is free to refuse to participate or to answer any questions, that he/she may stop at any
time without penalty, that care will not be affected by participation, that the IRB may be contacted for
questions or complaints, and that answers will be kept confidential. These key elements of informed
consent should not be eliminated when a project is exempt from review. Whenever appropriate, they
should be standard operating procedure.
With retrospective chart surveys, the major potential violation of the subject's rights would be a breach
of confidential information. When done with appropriate measures to "unlink" personal identifiers
from the data, this kind of research may be done without the participant's express consent because this
threat to his/her rights has been eliminated.
On the other hand, some studies which carry substantial risk, and for that reason are not eligible for
exemption, may in some cases, be carried out with a waiver of either informed consent itself, as in
some emergency medical research, or of documenting the verbal informed consent.
Finally, there are circumstances in which a study may not be eligible for exemption, but may
nevertheless allow for a modification in the consent process, such as a "short form" consent, or a
waiver of the consent process altogether.
Short form consent
A short form may be used in cases where the participant does not speak English. In this case, the short
form consent document must be written in the language of the participant. Since the short form is a
standard document, it is not necessary to obtain a new translation of this form for each study. The
study summary can be in English, and with the IRB's approval, may be the English version of the
consent form. Standard short form consents in a number of languages commonly encountered in
CCHHS affiliate sites can be obtained from the CCHHS Office of Research & Regulatory Affairs
(312-864-4821).
The full consent procedure must be presented orally to the participant in his/her own language. Each
oral presentation must be witnessed by a third person, who must sign the affidavit by the interpreter
that translated the English consent as well as questions and answers for the participant.
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It is preferable that the translator for the consent process be a certified medical interpreter. In general, a
family member or friend of the participant should not be asked to interpret. The investigator obtaining
the consent must be present during the translated consent procedure to answer questions.
When either the short form or a full translated consent is used, copies of both an English version of the
consent form and the signed translated or short form consent must be placed in the participant's
medical record.
These are the necessary steps for using a short form consent when the participant does not speak
English:
1. A person fluent in both English and the language of the participant, verbally delivers the
information contained in the full consent document (which may also serve as the study summary);
2. The short form document is signed by the participant (or the participant's legally authorized
representative);
3. The summary is signed by the person obtaining consent as authorized under the protocol; and
4. An affidavit of in translation is signed by the interpreter and a witness.
The participant should receive a copy of both the signed short form and the signed summary to keep.
As discussed later under "Translated Consents", this procedure will not ordinarily be acceptable when
the participant's native language is Spanish, and the investigator has reason to believe before starting
the study that a substantial number of Spanish-speaking participants will be enrolled. In this case, a
full consent translated into Spanish will be required. Additionally, if research activity is anticipated to
be conducted at one or more CCHHS sites where the dominant language spoken other than English is
something other than Spanish, the same expectations for language translation and interpretation will be
expected.
Informed consent without documentation
There are two conditions under which consent may be given without signing a consent form.
1) When participants are recruited because of sensitive, stigmatizing, or illegal characteristics keeping
their identities confidential may be crucial in obtaining their cooperation. If the only document in
which they could be identified is the written consent document, IRB permission may be requested to
waive written consent. This does not mean that there is no informed consent - investigators will still
prepare and carry out a consent process as in any other study. The written documentation, however, is
omitted.
2) If the research involves no more than minimal risk and the research procedures do not require
consent under non – research circumstances, the participant may be consented orally. A consent
“script” should be included and approved by the IRB and documentation should be placed in the
research record, indicating that the participant was consented orally.
Waiver of Consent - In a few circumstances, the consent process itself may be waived:
45CFR346 provides conditions under which the consent may be waived in part or entirely. For such a
waiver, there must be no additional risk, and no additional tests or procedures above and beyond what
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the patient would normally encounter. As a rule, such a waiver will not be granted unless there is
ample justification for omitting consent.
Such a justification would include:
(1)
that the research involves no more than minimal risk to participants;
(2)
that the waiver or alteration will not adversely affect the rights and welfare of the participants;
(3)
that the research could not practicably be carried out without the waiver or alteration; and
(4)
that whenever appropriate, participants will be provided with additional pertinent information
after their study participation concludes.
Not “practicably” falls on a continuum between “not convenient” and “not possible,” very close to the
“not possible” end. In the case of record review, this is often because the age of the records being
reviewed or the mobility of the patients makes it near impossible to contact them for consent. While
information on a consent may be excluded, false information is never allowed.
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INFORMED CONSENT FOR SPECIAL PARTICIPANT CLASSES
___________________________________________________________________
For several classes of research participants, the ability to give informed consent may be compromised,
either because the person is not considered competent to consent -- as with children or decisionally
impaired persons, or because the situation itself may be considered coercive, as with participants who
are detainees, prisoners or employees. For each of these classes of participants, care must be taken to
insure that consent to participate meets all the requirements of informed and voluntary consent.
Minors
In most cases, permission for a child to participate in research may be given by a parent or legal
guardian. In research that entails risky procedures, it may be necessary to obtain the permission of both
parents. In all cases, permission of both parents is desirable where feasible. If one parent is not
available, this fact should be noted on the consent form.
With children of an age to understand some aspects of research (usually considered to be around age
seven or older), and with adolescents, you must give the participant a developmentally appropriate
explanation of the research and ask for his/her assent. Children old enough to sign their names should
be asked to sign an assent line in the consent form.
If a child refuses to assent to research participation, in most cases, that decision must be respected.
However, when the research offers the child the possibility of a direct benefit that is important to the
health or well-being of the child and is available only in the context of the research, the IRB may
determine that the assent of the child is not necessary. Additionally, in such circumstances a child's
dissent, which should normally be respected, may be overruled by the child's parents, at the IRB's
discretion. There are some circumstances, even in this category of studies, in which a child's dissent
may be permitted to stand. For instance, when research involves experimental therapies for lifethreatening diseases such as cancer, if the likelihood of success is marginal and the probability of
extreme discomfort is high, a mature adolescent close to death may refuse the treatment and have
his/her wishes respected.
Note that most categories of exempt research apply also to studies of minors, with the exception of
interviews and surveys. Only observations of public behavior, in which the investigator and child do
not interact, may be exempted. If there will be interaction with the child, even via paper and pencil, the
protocol must be reviewed. Parental permission will also be required in most cases.
Adolescents legally defined as emancipated are permitted to participate in research without their
parents' permission. Research involving older adolescents who, under applicable law, may consent on
their own behalf for selected treatments (e.g., treatment for sexually transmitted infections,
drug/alcohol addiction, or emotional disorders) may also not require parental permission. The IRB will
determine for each project requesting such an exception if it may be allowed.
In these cases, investigators must:
1) explicitly request that the IRB make an exception to the requirement for parental permission; and
2) document for each case in which parental permission was not obtained why it was not possible to
obtain it. In addition, when adolescents are enrolled in complex research protocols, it may be
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advisable to make an ombudsman available to them--an adult not involved in the research who can act
as an advisor and advocate for the adolescent during his/her participation in the research.
In other research (e.g., research on child abuse or neglect), there may be serious doubt as to whether
the parents' interests adequately reflect the child's interests. In these cases, alternative procedures for
protecting the rights and interests of the children asked to participate must be worked out with the IRB.
Research with Minors who are Wards of the State
Research activity with minors who are wards of the state is permitted, only if three criteria are met:
1. Informed consent is obtained from their legal guardian;
2. The study design poses no more than minimal risk, meaning that the probability and magnitude
of 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; and,
3. The study is determined to have a direct benefit to the participants.
Persons Lacking Decision-Making Capacity
Persons recruited for research participation may lack decision making capacity due to a number of
circumstances: Having either a psychiatric disorder (e.g., psychosis, neurosis, personality or behavior
disorders), an organic impairment (e.g., dementia) or a developmental disorder (e.g., intellectual
disability) that affects cognitive or emotional functions to the extent that capacity for judgment and
reasoning is significantly diminished. In addition, persons under the influence of drugs or alcohol,
those suffering from degenerative diseases affecting the brain, or patients in extreme pain, may also be
compromised in their ability to make decisions in their best interests.
Under the Illinois Health Care Surrogate Act, decisions about medical care may be made by a
surrogate decision maker when the patient is judged to be incapable of making those decisions. A
surrogate decision maker is an adult with decisional capacity who is available upon reasonable inquiry
and is willing to make decisions on behalf of the patient. When no there is no person with valid and
effective Power of Attorney for Health Care for the patient, a surrogate may be identified according to
the following priority:
1. The guardian of the patient
2. The spouse of the patient (common law spouses are not recognized in Illinois, but may qualify
under category #7)
3. Any adult son or daughter of the patient
4. Either parent of the patient
5. Any adult brother or sister of the patient
6. Any adult grandchild of the patient
7. A close friend of the patient [Note: this is defined as any person 18 years of age or older who has
exhibited special care and concern for the patient and who presents an affidavit to the investigator
stating that he or she:
(i) is a close friend of the patient;
(ii) is willing and able to become involved with the patient's health care and
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(iii) has maintained such regular contact with the patient as to be familiar with the patient's
activities, health, and religious and moral beliefs. The affidavit must also state the facts and
circumstances that demonstrate familiarity];
8. The guardian of the patient’s estate.
Surrogate decision makers are expected to make decisions that conform as closely as possible to what
the patient would have done or intended under the circumstances. If the patient's wishes are unknown,
the surrogate should base a decision on the patient's best interests, weighing the burdens and benefits
of treatment options according to the information that would be available to a competent patient.
In this context, surrogate decision makers may be asked to give permission for enrolling persons
lacking decision making capacity patients in clinical research when the research holds outs some
potential for personal benefit to the patient. In order to enroll a person lacking decision making
capacity into a clinical study with a surrogate decision maker's permission, the investigator must take
these steps:
1. Determine if the patient is competent to consent to participate in research. Note that adults may not
be presumed "incompetent" to consent for themselves based on such broad factors as whether they are
institutionalized or have a certain diagnosis. Rather, the investigator must determine if the person can
understand and consent to the research.
This means determining if the person has the ability to understand the nature and consequences of a
decision regarding research participation, and the ability to reach and communicate an informed
decision in the matter. Specifically, using assessment procedures described in the protocol, the
investigator will determine if the patient understands each of the following:
the nature and extent of his/her proposed research participation
the potential risks and benefits of participation
the alternatives to participation in the research
the right to refuse to participate and the right to withdraw from the study
The results of this assessment must be documented.
2. Take steps to identify an appropriate surrogate decision maker and document that surrogates higher
in priority are not reasonably available.
3. Obtain documented informed consent from the surrogate for the patient's participation in the
research.
4. Obtain signed, dated documentation from a physician not involved in the study that steps 1-3 have
been appropriately carried out, and that the research holds the potential to benefit the patient
personally. This documentation may also be included as part of the consent form, or as an attachment.
Special considerations apply to obtaining surrogate consent for a person lacking decision-making
capacity:
The identity and relationship of the surrogate decision maker to the patient must be documented on the
consent form. The affidavit required of the "close friend" surrogate must be attached to the consent
form.
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In the consent process, the surrogate decision maker must be informed that he/she will be asked to
make decisions on behalf of the patient in a manner that conforms as closely as possible to the known
wishes of the patient. If the patient's wishes are unknown, the surrogate is expected to make decisions
in accordance with the patient's best interests, weighing the risks and potential benefits of research
participation and those of alternative available treatments.
When two or more individuals are members of the highest possible surrogate priority category, they
must reach consensus on the patient's research participation before the patient is enrolled. If the patient
objects to a particular individual acting as the surrogate decision maker, then that person may not act as
that patient's surrogate decision maker for research participation. If this individual represents the
highest possible surrogate priority category, then the patient may not be enrolled in the study.
When obtaining consent from a surrogate for a person lacking decision making capacity, the
investigator is expected to obtain the participant's assent, if possible. The participant must be present
during the entire consent procedure and the participant's presence must be documented in the consent
form. If a decisionally impaired adult refuses to assent to research participation, that decision must be
respected.
Waiver of Consent - Conditions and Considerations
CCHHS does not permit waivers of informed consent in emergency medical research involving
patients unable to give informed consent. However, consent from an appropriate surrogate (under IL
law) may be acceptable.
Detainees
Detainees and prisoners can only be asked to participate in research which could potentially benefit the
persons themselves or a group to which they belong. No research with prisoners or detainees may be
exempted from review. Consent procedures must include clear language that there will be no
repercussions to the potential participant should he/she decide not to participate, and no special
consideration (such as early release) will be given should they decide to participate. Procedures for
maintaining strict confidentially should also be used, and clearly described in the consent form.
Research with detainees also requires that the convened IRB meeting at which it is considered include
a prisoner advocate. For this reason, detainees may not be enrolled in an approved protocol, nor may
previously enrolled participants be continuously followed who become incarcerated after enrollment,
unless inclusion of this population was specifically requested and approved. Responsible Investigators
must instruct research personnel about this restriction, and must remind them that detainees when
hospitalized, are usually distinguishable from the general inpatient population by the presence of a
Sheriff's deputy, the use of restraints, and with outpatients, and a Department of Corrections or
Juvenile Detention Center uniform worn by the detainee.
Employees
Consent procedures used for employees must include clear language that there will be no repercussions
to the potential participant should he/she decide not to participate, or once enrolled, decide to
discontinue participation. Procedures for maintaining strict confidentially should also be used, and
described in the consent form.
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GUIDELINES FOR OBTAINING INFORMED CONSENT
____________________________________________________________________
The responsibility for the proper administration of the consent process lies with the CCHHS
Responsible Investigator and the Principal Investigator(s) involved in the project.
Who may obtain informed consent?
Obtaining informed consent is the responsibility of investigators trained to carry the process out
correctly. For this reason, informed consent may only be obtained by persons who:
1. Are named as investigators on the application for IRB approval
2. Are specifically trained in the principles of informed consent
3. Have been trained to obtain and document informed consent according to these guidelines
4. Are knowledgeable about the study for which the consent is being obtained
5. Are able to communicate with the prospective participant, directly or through a qualified interpreter
6. For the purposes of the study in question, are supervised by the named Responsible Investigator.
Persons who meet these criteria may rely on qualified interpreters to obtain informed consent from
participants who do not speak English (see sections on "Translated Consent" and "Short Form
Consent"). When an interpreter is used, the person obtaining consent must be present during the entire
process to answer any questions the prospective subject might have.
Studies which employ persons who do not meet these criteria to obtain consent will be considered noncompliant and subject to suspension or termination by the IRB.
Informed Consent is A Human Interaction, Not a Piece of Paper
The written document is only a guide to what a research investigator will say to the prospective
participant, as well as a record of what was communicated. The information in the consent document
must be presented in a face-to-face dialog, with abundant opportunities for the prospective participant
to ask questions and for the investigator to amplify the explanation as needed. Information on the
consent form must be presented in such a manner that a person with a second grade education can
understand it. The consent form should reflect the content and language actually used when talking
with the participant.
Consider the Setting
Obtaining informed consent for research should be a meaningful interaction. It should not be carried
out as if it were pro forma or just another piece of necessary paperwork. To this end, the person
obtaining consent should find a setting in which distractions and interruptions are minimized and
privacy is maximized. This is especially important when a medical condition of the prospective
participant is to be studied.
Translated Consent
Although the IRB does not require that all consent forms be translated to languages other than English,
if there is anticipation that recruitment will occur from a population with a substantial number of nonCCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
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English speakers, translated consent forms are required. Particular consideration should be given to
estimating the likelihood of many Spanish-speaking participants in the recruitment pool, as that is the
most frequently spoken language after English, among CCHHS patients. Exclusion of potential study
volunteers because of an easily-anticipated language barrier might violate the principle of
inclusiveness in research.
The CCHHS IRB has adopted a guideline that any study designed to recruit at CCHHS Affiliate sites
should anticipate that a significant portion of the patient population will not speak English at all, or
will be limited English speakers. The IRB will judge the need for Spanish or other language
translations in consent forms according to the populations proposed for recruitment in each protocol
reviewed. The most common language spoken among CCHHS patients, other than English is Spanish,
followed by many other languages. Translation of consent documents into Spanish or other languages
should be factored into the study design in most cases, especially if recruitment is to occur anywhere
on the John H Stroger campus site. When a full translated consent is required, investigators are
expected to have the work done by a professional translator. If you need recommendations for such
services, contact the Office of Research & Regulatory Affairs at 312-864-4823.
For non-English-speaking participants, when a full translated consent document has not been prepared,
the consent procedure may be translated verbally by an interpreter, with that person also signing the
consent form and a short form consent document in the participant's own language.
For both short form and translated consent procedures, it is preferable that the translator for the consent
process be a certified medical interpreter. A family member or friend of the participant should not be
asked to interpret. The investigator obtaining the consent must be present during the translated consent
procedure to answer questions.
When either the short form or a full translated consent is used, copies of both an English version of the
consent form and the signed translated or short form consent must be obtained and filed in the
participant’s study record, and in some cases, into their medical record as well.
Making Consent Forms Understandable
Effective communication requires a conversational exchange that includes asking respectfully to see if
the information is understood. The average reading skills of Americans are no higher than an eighthgrade equivalent. Most already-prepared handouts, questionnaires, and consent forms are written at
10th grade level or higher. This means that the majority of participants in any setting are less likely to
be able to read and understand such materials. Written materials should be prepared at the lowest
possible level of reading difficulty, generally fifth grade level or lower, to the extent possible. Please
note that a Word document can be checked for the reading level of its content by selecting “show
readability statistics” in the “proofing” options list under the “file” tab (see appendix for more details).
Additionally, researchers and clinicians should consider using non-written materials to communicate,
where possible.
Write the consent form as a script for a face-to-face discussion with the prospective participant.
Always keep in mind that informed consent is a process, with face-to-face discussion the most
important part. The consent form is only a documentation of that process. If you write the consent form
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to be the same as the information you will give verbally, you will more likely use simple, direct
language that anticipates and answers the prospective participant's need for information.
Be brief but give complete basic information
In particular, you need to avoid an information overload which leads prospective research volunteers to
stop paying attention or to feel overwhelmed by the detail. Much scientific detail can be reworded or
eliminated without compromising the needed information.
Make forms less dense and easier to read
This means avoiding long words and complex phrasing. It also means using the active voice instead of
the passive voice; using common words; making clear the links of logical sequences and of cause and
effect (even if it makes the sentence longer); and repeating key or new ideas.
Be clear and provide the background information needed
Ask yourself, "What questions am I trying to answer? What background information does he or she not
have, but needs, to understand this?" Asking those questions may help to eliminate jargon, specialty
terms and ideas not essential to making an informed decision. Also, avoid euphemisms. Research
should be called "research", not "study" or "project", all the more so because many prospective
participants are suspicious of research and need to feel that the investigator is being completely open
about his/her intentions.
Include only relevant information
If a coordinating center (perhaps national), includes language for all possibilities, make sure to review
the content and remove any content that does not pertain to your specific protocol and thus irrelevant
to the prospective participant. For example, if you are not participating in a given sub-study, do not
include content about the sub-study at all.
Format consent forms to help comprehension and memory.
Use headings and indentations to clearly mark sections of the form
Display the presentation of study visits/procedures in a simple tabular format or flow sheet
Include prevalence estimates for potential study drug side effects if applicable; (for example, 1
of 100 people may get a rash)
Use bolding or underlining to emphasize key words
Use extra spacing between topics
Repeat important or difficult-to-understand points
Avoid using all uppercase letters
Keep the type size reasonable
Use large margins and plenty of empty space
Make sure the copy quality is good.
Although these formatting strategies are likely to require more paper, they are also likely to increase
ease of reading, comprehension, and recall of the material.
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When a prospective participant's literacy skills are very limited
There are a number of strategies that can be used to enhance the consent process with persons whose
literacy skills are limited:
 "Next day consent": Carry out the initial discussion a day before the person actually gives consent
and is enrolled. This gives him/her a chance to mull over the explanation, think of questions, reread
the documentation and consult with family members.
 Use of flip-cards -- large format cards with key points and relevant graphics and diagrams -- to
accompany the discussion.
 Use of patient-centered videotape or audiotape.
 Develop and use community-based methods to inform people before they are asked to participate
Documenting Consent
Consent language examples are provided with an intent to suggest acceptable wording and format for
use in consent forms. Investigators must rewrite, reformat or edit these examples to suit your specific
study. All consent forms must, however, include all the essential elements of informed consent
described, previously.
Consent form language is often developed by study sponsors. These documents should be reviewed
carefully, as they are often in need of rewriting, in order to include only the truly essential points in a
more understandable format.
Consent forms must be reproduced on CCHHS institutional letterhead. As part of the project
explanation given to the prospective participant, they must be informed that s/he will receive a copy of
the consent form and it should be documented that they got or refused a copy.
Informed consent must be obtained by an appropriately trained professional listed as an investigator on
the research project. The consent form must be signed by the participant and the person obtaining the
consent. When an interpreter is used, the interpreter should sign an affidavit and the participant should
sign the consent document that was translated. When the short form consent is used, a witness to the
verbal explanation must also sign that document. The person witnessing the consent must have no
professional or personal interest in the research to be carried out. The ORIGINAL signed copy must
be attached to the participant's research chart, the participant, or their representative receives a copy; a
record of consent must be forwarded to Pharmacy Services when applicable. The Principal
Investigator must retain copies of the signed consent forms for at least ten years after the end of the
study. CCHHS IRB members, the staff of the Office of Research & Regulatory Affairs, and
appropriate federal regulators have the right to access all study documents which are kept in the files of
the Principal Investigator(s).
The consent form must contain the names and telephone numbers of persons to contact should the
participant have any questions or complaints about: 1) the research itself; 2) medical questions; and 3)
human participant protections. The contact person for categories 1 and 2 may be the same person, but
it must be clear in the consent form that both types of questions should be referred to him/her. For the
third category, this should be the phone number for the CCHHS IRB, (312) 864-0716 or (312) 8644821.
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FORGOING PARENTAL CONSENT IN RESEARCH WITH MINORS
____________________________________________________________________
Federal regulations require consent to be obtained from parent(s) or guardian(s) when children are
being asked to participate in a research study (45 CFR 46/408 and 21 CFR 50/55). Not all minors are
defined as children. There are three circumstances when parental consent is not required for a minor.
1. WAIVER OF INFORMED CONSENT (45 CFR 46/116) – each of these conditions must
hold.
 Research is not greater than minimal risk
o If the research planned is a survey, it may not collect identifiable data which
would put the participant at risk. Participation in the research cannot pose a risk
of significant emotional upset requiring discontinuation or counseling.
 Research as planned, does not affect the rights of participants
 Not practicable to obtain consent
o Explain/justify why it is not practicable;
o Explanation must convey how it is not practicable - it does not have to be
impossible, but it must be much more than inconvenient.
 Participants will be told after the fact, if appropriate.
2. 408 WAIVER (Not for INDs) (45 CFR 46/408) – both conditions must hold.
 Parental consent is not a reasonable requirement; (example, abused/neglected
children/youth)
o State/justify why it is not a reasonable requirement
 There is an appropriate substitute mechanism to protect the children/youth
o Provide the name and position of the substitute.
3. MINOR (<18), but NOT a CHILD (defined by IL law), can Consent
Under IL law, a minor is not a child and can consent if they are emancipated or mature minors
(legal status) (750 ILCS 30/1). Minors can also consent to medical treatment in certain
situations (410 ILCS 210) including:
 Minors who are married, pregnant, or parents for medical/surgical procedures
 Emergency treatment
 Reproductive health, including birth control services for minors who are married,
parents, pregnant, referred by physician, clergy, Planned Parenthood agency, or to
prevent serious health hazard
 HIV treatment (diagnosis, counseling, NOT prevention – see sexually transmitted
infections [STI] for prevention, which is also treatment)
 Sexual assault survivors
 Minors ≥12 for STI counseling, diagnosis or treatment
o Provide an explanation of how participation in the research planned (including
interviews and surveys), simultaneously serves as ‘treatment.’
 Minors ≥12 for counseling or psychotherapy for mental illness
 Minors ≥12 for medical care, counseling, or treatment for substance abuse
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RECRUITING RESEARCH PARTICIPANTS
__________________________________________________________________
Advertising for Volunteers
Posters, flyers, mailings and newspaper ads are all legitimate methods to inform people of studies they
might be interested in joining. Increasingly, social media is another tool in use for recruitment
advertising and other aspects of research. Such advertising using any method must be done carefully,
however, to avoid being misleading or possibly coercive. All advertising/recruitment materials must
also be reviewed and approved by the IRB.
Remember that direct recruiting advertisements are considered to be part of the informed consent and
participant selection processes. IRB review is necessary for advertising materials to ensure that the
information is not misleading to prospective participants. This is especially critical when a study may
involve participants who are likely to be vulnerable to undue influence. When direct advertising is to
be used, the IRB reviews the information contained in the advertisement and the mode of its
communication, to determine that the procedure for recruiting participants is not coercive and does not
state or imply a certainty of a favorable outcome or other benefits beyond what is outlined in the
consent form and protocol.
The IRB must approve the final copy of printed or electronically posted ads. The IRB will evaluate not
only the verbal content, but the relative size of type used and other visual effects. When ads are
produced for broadcast, the IRB should review the final audio or video tape. No claims should be
made, either explicitly or implicitly, that the drug, biologic or device is safe or effective for the
purposes under investigation -- remember that this usually is the experimental question under study, so
no forgone conclusions may be implied.
Claims also cannot be made that the test article is known to be equivalent or superior to any other drug,
biologic or device. Such claims would not only be misleading, but would also be a violation of the
FDA's regulations concerning the promotion of investigational drugs or devices. Advertising for
recruitment into investigational drug, biologic or device studies should not use terms such as "new
treatment", "new medication" or "new drug" without explaining that the test article is investigational.
A phrase such as "receive new treatments" implies that all study participants will be receiving newly
marketed products of proven worth. Advertisements should not promise "free medical treatment"
when the intent is only to say participants will not be charged for taking part in the investigation.
Generally, any advertisement to recruit participants should be limited to the information the
prospective participants need to determine their eligibility and interest. When appropriately worded,
the following items may be included in ads:






The name and address of the clinical investigator and/or research facility;
The condition under study and/or the purpose of the research;
In summary form, the criteria that will be used to determine the eligibility for the study;
A brief list of participation benefits, if any (e.g., no-cost health examination);
The time or other commitment required of the subjects;
The location of the research and the person or office to contact for further information.
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Recruiting for a Study versus Clinical Referrals
The CCHHS IRB requires that all organized recruitment of potential study participants at CCHHS
facilities be reviewed and approved by the IRB prior to recruiting patients. Organized recruitment
would include stationing recruiters in clinic waiting rooms or designated hospital areas; posting flyers
or handing out recruiting leaflets.
This is in contrast to an individual medical provider telling a patient during a clinical interaction about
a research study available at another institution. As long as only descriptive information is given to the
patient (i.e., a summary of the research, and the name and phone number of the physician conducting
the trial), without any stated or implied endorsement of the research, the IRB considers this interaction
to be a clinical referral, not organized recruitment.
Sometimes care providers are asked by colleagues from other institutions to provide lists of names and
addresses or phone numbers of patients who may meet inclusion criteria for a study being conducted at
that institution. Releasing the names and addresses of patients to someone not employed by CCHHS,
who does not have any clinical reason to know this information, is a violation of the patient's rights to
privacy and confidentiality. Only employees with a clinical reason to know about patients' conditions
should contact them about possibly participating in research. That means CCHHS health professionals
may speak to, call or write their own patients and ask permission to forward their names to a colleague,
without breaching the confidentiality of the provider/patient relationship. Likewise, someone directly
supervised by the health professional, a resident or a nurse for example, could make this initial contact.
Until the patient gives permission to be recruited, however, the off-site colleague and/or their
employees should not be given this information.
If a physician or other health professional wants to facilitate the recruitment of a number of patients for
a particular study that is outside of CCHHS, or if a health professional wants to identify patients
eligible for an outside study through a record review, advertise a study in the clinic, or instruct other
professionals or residents to recruit patients for such a study, this is a collaboration in research and is
overseen by the IRB. The professional must agree with the outside PI that s/he will be the
“Responsible PI” within CCHHS. S/He may submit a letter to the chair describing the study along with
the protocol and IRB approval from the other institution and ask that the consent forms and
advertisements be accepted and that we rely on the other institution for annual review. The chair will
forward the protocol for full review as deemed appropriate.
The CCHHS investigator (RI) must consider how the participants will be recruited in order to comply
with the Privacy Rule.
a) They may be read a script by CCHHS personnel “Do you want to participate in study XYZ at XXX
institution?” They must sign an authorization for release of Protected Health Information, before their
name is given to the other institution. Patients’ names may not be pulled from records and disclosed
without patient authorization.
b) Alternatively, they may be asked by CCHHS personnel whether they wish to participate and then be
given an appointment card (or postcard) which they take (or mail) themselves to the other institution.
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c) The CCHHS patient may not be consented by the CCHHS employee, but rather by an employee of
the other institution who has a clear ID.
d) The consent should not be on CCHHS letterhead nor shall it mention CCHHS as a collaborating
institution or the CCHHS Responsible Investigator as a collaborating researcher.
If a CCHHS employee is to be an author on the study, or if otherwise substantively involved, whether
or not compensated for participation, the CCHHS employee is a collaborator and the protocol must be
reviewed in the way in which protocols involving research at CCHHS are reviewed.
If a CCHHS employee is participating in the study as an employee of another institution at which the
research is done and if that research involves CCHHS patients, it is a collaboration and may not be
reviewed as “recruitment only”.
If a researcher at another institution also has privileges at CCHHS, that person may be the responsible
investigator however, the protocol would then be a CCHHS protocol and would not be eligible for
“recruitment only” review.
In order that the recruitment only protocol may be located in the IRB filing system, it is processed as
an exempt research project. That is, it is documented, but there is no additional reporting. This is the
case, regardless of the review level at the protocol’s home institution.
"No" Means No
Prospective participants who have declined to participate in a research study may not be approached
again for that study. It is an infringement of a person's autonomy not to accept that person’s decision,
and any further approaches could be seen as coercive. If you wish to include data about a person who
declines participation, please consult the CCHHS policy on “Persons who have declined.”
Payments to Participants
Ads may state that participants will be paid, but should not emphasize the payment or the amount to be
paid. In general, the IRB recognizes that the legitimate costs to patients who participate in research -car fare, lost wages, child care, and food -- may be appropriately reimbursed without creating a
coercive situation. In general $10 per hour including time used in transportation, plus child care and
food costs are acceptable. If a study runs through mealtime, meals may be provided or paid. In some
cases, additional payments may be considered, but this determination will be made for projects on a
case-by-case basis. Acceptable forms of payment include cash, gift cards, pre-loaded debit cards,
money orders or electronic deposits.
In addition, with studies lasting more than a few days, it is not appropriate to make full payment
contingent upon completion of the study. It is appropriate to hold a small portion of the payment until
the completion of the study for additional debriefing or wrap up, as long as this "bonus" is not so large
as to be coercive. Reimbursement for costs and the payment schedule must be described in the consent
document.
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INCLUSION OF WOMEN AND PERSONS OF COLOR IN RESEARCH
___________________________________________________________________
Historically, many ethical abuses of human beings have occurred in research, as have numerous
instances of unjust and discriminatory exclusions of women and persons of color in scientifically
beneficial research. Many well-designed, highly regarded scientific studies, with clinical benefit and
minimal risk have occurred with most participants being adult males, and overwhelmingly white.
Since a primary aim of research is to provide scientific evidence leading to a change in health policy or
a standard of care, it is imperative to determine whether the new intervention or therapy affects women
or men or members of various ethnic groups and their subpopulations differently.
The United States has a well-documented history of unethical research practices with vulnerable and
marginalized populations. Research experimentation was performed with male and female slaves, and
post-reconstruction, “Jim Crow” era efforts, most notably, the Tuskegee Study, which took place from
1932-1972, officially sponsored by the US Public Health Service. Other documented ethical abuses
have taken place with Native Americans, immigrants, mentally challenged and physically disabled
persons, children, prisoners, military personnel and other vulnerable employees.
Lessons learned from the Tuskegee study, and the genocidal practices revealed from the post-World
War II Nuremberg trials on crimes against humanity, helped to inform and frame the key principles
described in the Belmont Report, which continues to serve as a guide for how research activities are to
be ethically conducted. Further review and reconsideration of inclusion criteria for research has led to
additional federal guidance on recruitment of women, including pregnant women, children and diverse
ethnicity representation in research efforts.
The National Institutes of Health and the Food and Drug Administration have guidelines intended to
ensure that federally-supported or federally-regulated biomedical and behavioral research involving
human participants will elicit information about individuals of both genders and of diverse racial and
ethnic groups and, in the case of clinical trials, to examine differential effects on such groups.
Historically, the Cook County Health & Hospitals System has been and remains the leading safety-net
health care provider for this geographic area, and a disproportionate share of its patient population is
comprised of vulnerable and marginalized persons. CCHHS is committed to inclusiveness in all forms
of research. The leading priority of the current CCHHS mission statement is to: improve health
equity, which is achieved when every person has the opportunity to attain his or her full health
potential and no one is disadvantaged from achieving this potential because of social position or other
socially determined circumstances. (Source: April 2016 CCHHS Strategic Planning 2017-2019;
Institute of Medicine).
For these reasons, investigators are asked to address the language, linguistic, literacy/health literacy,
logistical and practical needs of patients whose participation in research initiatives is desired. That is
why investigators are asked, when making yearly progress reports to the CCHHS IRB, to provide data
on the gender, racial and ethnic makeup of participant samples enrolled in approved studies of any
type. Investigators are encouraged when possible, to utilize principles of community-based,
participatory research in the conceptual design, implementation and evaluation of their research
initiatives, and where feasible and possible, establish formal community advisory boards, or other
vehicles for initial and ongoing patient/participant input into all aspects of the research activity.
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Inclusion of Pregnant Women
The US Department of Health and Human Services, in an effort to improve the quality and access of
pregnant women to participate in research, changed its research policy, from a presumption of
exclusion to one of inclusion of pregnant women. Pregnant women may not be categorically excluded
from clinical trials based solely on the pregnancy. If there is evidence that either the woman or fetus
may be harmed by participation in a trial, then pregnant women may be excluded. An explicit rationale
for exclusion is required in the proposal for research.
Consult 45CFR46 Sub Part B for the revised regulation.
If women (or men) are not to conceive a child while on a research study, they must be told and given
birth control information. Additionally, they should be told how long after completion of a study they
should prevent conception.
They should be told what will take place if they do conceive a child. For example, that they will not be
permitted to continue the study drug or that, with their permission, their pregnancy will be followed by
the sponsor.
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INCLUSION OF CHILDREN IN RESEARCH
____________________________________________________________________
The National Institutes of Health (NIH) now requires that children be included in all its sponsored
research unless there are scientific and ethical reasons to exclude them. The goal of this policy is to
increase the participation of children in research so that adequate data will be developed to support the
treatment modalities for disorders and conditions that affect adults and may also affect children.
Therefore, proposals for research to be funded by NIH involving human participants must include a
description of plans for including children. If children will be excluded from the research, the
application or proposal must present an acceptable justification for the exclusion.
Justifications for Exclusions
It is expected that children will be included in all research involving human participants unless one or
more of the following exclusionary circumstances can be fully justified:
1. The research topic to be studied is irrelevant to children.
2. There are laws or regulations barring the inclusion of children in the research.
3. The knowledge being sought in the research is already available for children or will be obtained
from another ongoing study, and an additional study will be redundant.
4. A separate, age-specific study in children is warranted and preferable.
5. Insufficient data are available in adults to judge potential risk in children (in which case one of the
research objectives could be to obtain sufficient adult data to make this judgment).
6. The study design is aimed at collecting additional data on pre-enrolled adult study participants (e.g.,
longitudinal follow-up studies that did not include data on children).
7. Other special cases justified by the investigator and found acceptable to the IRB.
When including minors indicate whether the study is of minimal risk (45 CFR 46.404) or for the
benefit of the minor (45 CFR 46.405). If it is neither, please consult the IRB before considering the
study.
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MAINTAINING CONFIDENTIALITY – RESPECTING PRIVACY
__________________________________________________________________
The need for confidentiality exists in all studies in which data are collected about identified
participants. Researchers must be able to give participants honest assurances of confidentiality and
make specific provisions to maintain it. In most research, assuring confidentiality is only a matter of
following some routine practices: substituting codes for identifiers, removing face sheets (containing
such items as names and addresses) from survey instruments containing data, properly disposing of
computer sheets and other papers, limiting access to identified data, impressing on research staff the
importance of confidentiality, and storing research records in locked cabinets, and/or encrypted,
password–protected electronic files.
In some studies, where participants are selected because of a sensitive, stigmatizing, or illegal
characteristics (e.g., persons who have sexually abused children, sought treatments in a drug abuse
program, or tested positive for HIV) keeping the identity of participants confidential may be as or more
important than keeping the data obtained about them confidential.
In many observational and retrospective studies, data is recorded without any individual identifiers,
and thus may be exempt from IRB review. Persons performing such a study must confirm its exempt
status with the Chair of the CCHHS IRB. If participant names will be recorded by the investigator for
follow-up (either for further record reviews or for personal contact), then this research requires IRB
review. In such instances, the IRB must determine whether the participant's consent must be obtained
before the researcher gains access to the records.
Study participants’ privacy and confidentiality are taken very seriously by the CCHHS IRB.
According to federal regulations, one criteria that must be met in order to obtain IRB approval includes
adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data (45
CFR 46.111(a)(7)). This is why the IRB asks for a plan to protect privacy and confidentiality in the
application. In addition, this plan must be explained to research participants as part of the informed
consent process (45 CFR 46.116 (a)(5)). Once the IRB approves the plan, researchers must follow
what they have promised to the IRB and to study participants in the informed consent document.
What is privacy?
 Respecting an individual’s right to be free from unauthorized or unreasonable intrusion,
including control over the extent, timing and circumstances of obtaining personal information
from or about them.
 To protect privacy, provisions should include: ensuring that the conditions under which a
procedure is performed or information is collected afford protections against interactions with
participants being witnessed, overheard or inadvertently intercepted or viewed and limiting the
information being collected to only the minimum amount of data necessary to accomplish the
research purposes.
What is confidentiality?
 Respecting a potential or current participant’s right to be free from unauthorized release of
information that the individual has disclosed in a relationship of trust and with the expectation
that it will not be divulged to others without permission in ways that are inconsistent with the
understanding of the original disclosure.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
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
To maintain confidentiality, provisions should include: designing studies to maximize
confidentiality to avoid unintentional and unauthorized release or other disclosures and
maintaining the researcher’s agreement with the participant in the informed consent about how
the participant’s identifiable private information will be handled, managed, and disseminated.
What is an identifier? According to HIPAA, Protected Health Information, or PHI, includes:
 Names (including initials)
 Account Numbers
 Address (more precise than just a state)
 URLs
 Any Date (except year)
 Facial Images
 Medical Record Number
 IP Address
 Phone Number
 Vehicle ID
 Fax Number
 Certificate or License Numbers
 Social Security Number
 Device ID / Serial Numbers
 Email Address
 Biometric ID
 Health Plan ID
 Any Other Unique ID/Code
How do I do this?
 When designing your study, ensure conditions where participants can’t be overheard or seen
during procedures/interventions, limit data collected to only the minimum amount necessary to
accomplish your research goals, and avoid unintended/unauthorized disclosures. Include a plan
on how participant information will be handled, managed, and disseminated.
 Submit your plan to the IRB as part of your application and informed consent for approval.
 Maintain the agreement with the participant as described in the informed consent, and maintain
the approved plan you have submitted to the IRB.
What does this mean?
 If you describe to the IRB and the participant that there will be no identifiers linked to their
research data, make sure that none of the identifiers are used. This includes making sure the
consent form (with the participant’s signature) is not attached to the same folder as the deidentified research data.
 If your research requires identifiers, disclose this to the IRB and the participant.
 It is good practice to assign a random number to each participant and maintain an enrollment
log under lock and key to keep track of study participants in order to keep research data
separate from identifiers.
The CCHHS IRB does not permit the collection of Social Security Numbers without justification
and express approval. SSN should be removed from date (in those limited cases of approval as soon as
feasible).
The Certificate of Confidentiality – The Secretary of Health and Human Services may issue
Certificates of Confidentiality under Section 301(d) of the Public Health Service Act (42 USC 241(d)).
These Certificates are intended to protect researchers from compelled disclosure of the identities of
research subjects, but do not preclude the voluntary disclosure of this information. The Secretary has
delegated the authority to issue these Certificates to all Public Health Service agencies.
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PREPARING THE RESEARCH PROTOCOL
____________________________________________________________________
The research protocol is a detailed description of how and why the research will be carried out.
If the research is part of a grant proposal, include the grant application or, the methods section of the
grant application.
Safety Monitoring in Clinical Trials
When a new drug or treatment is being tested, there should be a mechanism to monitor the safety and
efficacy of the trial at intervals throughout. Most multisite trials sponsored by a federal agency or
pharmaceutical company will have a central Data Safety Monitoring Board which will periodically
check to see if unexpected patterns of adverse reactions can be discerned, or if the differences between
treatments are so large that it is more ethical to stop the trial than to continue it. Even with trials which
are locally designed and carried out, periodic safety monitoring can be built into the protocol without
jeopardizing experimental control. For instance, the pharmacy department might be asked to provide,
at certain accrual points, an unmasked code to an independent investigator (not the Responsible
Investigator or other person directly carrying out the trial), who could use interim results and adverse
event information to make a recommendation as to whether the trial should continue. If your protocol
includes such a safety monitoring mechanism, be sure to describe it.
CRITERIA USED BY THE CCHHS IRB TO REVIEW PROTOCOLS:
A. The acceptability of the study will depend upon its relative merits of, and the need for, the specific
investigation.
B. The description of the protocol must:
1. Highlight the need for the study, document any pertinent work in the field and any conflict in
the area under investigation.
2. Carefully define the end point in the study and the circumstances under which the study may
be interrupted (e.g. frequency of expected adverse effects and level of statistical significance
necessary to terminate the investigation).
3. Define the patient population, sampling methodology and criteria for inclusion/exclusion to
reduce any possible group bias.
4. Make clear any likely risks and benefits to individual subjects and to the class(es) of patients
being studied.
5. Use of placebo designs must be fully justified. Placebo studies may be appropriate where
there is no known therapy for a particular condition. When a proven effective therapy exists,
however, withholding that therapy for the sake of making a comparison of a new drug to a
placebo is not justifiable.
The CCHHS IRB may ask consultants outside its membership to review any studies for which
additional expertise is needed. It may also designate a "Review Subcommittee" to monitor certain
studies for which there is special concern about risks or feasibility.
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PREPARING THE APPLICATION
________________________________________________________________________________
The goal is to facilitate a constructive review of research. The IRB process is intended to be an
opportunity to ensure that the rights of the human research participants are protected
Note: Autumn-2016 is the expected launch of IRBManager, which is a web-based management
system of application submissions and tracker of the review and approval process. Forms and
instructions are preloaded for easy access and use; the system also has capability to accept uploaded
accompanying documents. The instruction manual for IRBManager will soon be accessible online
and a link placed in the appendix of this document. More information and training is forthcoming!
HOW TO APPLY FOR IRB REVIEW
1. Obtain current IRB Protocol application forms from the CCHHS intranet, or via email. Five
copies (one original, four copies--collated sets) of the completed forms, budget and protocol
must be submitted to the CCHHS IRB at present.
2. IRB applications must be completed and submitted to Room 333 Hektoen Building, 627 South
Wood Street.
3. Meetings generally take place on the first and third Tuesday of the month. For consideration at
a meeting, new applications must be submitted on the Monday prior to the scheduled Tuesday
meeting for reviewer assignment. Amendments and progress reports need to be submitted two
weeks ahead of the next scheduled meeting for adequate review time. Check with the IRB
office for the schedule of the meetings.
4. The application will be reviewed for completeness by the staff and assigned an IRB log number
for tracking purposes.
5. Applications that are incomplete do not contain adequate information to determine what is
being done, or are missing consent form documentation may be returned without action,
informing the RI of the missing elements.
6. The staff provides an administrative review of all IRB Protocol applications.
7. The IRB Chair or designee reviews applications and supporting materials and determines the
level of review required. Protocols deemed eligible for expedited review do not require a
convened meeting of the IRB to be approved but approval is acknowledged at a convened
meeting.
8. Upon receipt of the application ascertained as complete, the Chairperson of the CCHHS IRB
will refer it directly to one or more IRB members for report and recommendation.
9. During the review process the investigator may be asked to explain some elements of the IRB
Protocol application and may be requested to provide modifications. The reviewing CCHHS
IRB member(s) may discuss the merits of the project. The reviewing member(s) may ask
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
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questions and request changes or corrections in the project and consent form. Such changes or
corrections must be made by the investigator(s) before the review process proceeds to the next
step.
10. The IRB reviewer or Board will determine the level of review that is required for acceptance of
the requested modifications.
11. After the reviewing member(s) complete their review of the research project, it is presented at
the next convened meeting of the CCHHS IRB. The reviewing member(s) report their findings
and recommendations. Recommendations are voted upon by the entire CCHHS IRB.
Occasionally, investigator(s) may be asked to present and discuss the project before the
CCHHS IRB.
12. All concerns or revisions/modifications that need to be addressed are communicated to the
principal/responsible investigator in writing by staff on behalf of the IRB.
13. If a protocol is rejected by the IRB, the PI may appeal the decision to the IRB by writing the
Chair. The PI is invited to an IRB meeting where he may further clarify misunderstandings or
offer justification that was not initially understood by the Board. A decision of the IRB may
change but may not be overruled.
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RESPONSIBILITIES AFTER APPROVAL – INCLUDING DATA SECURITY
___________________________________________________________________
Once a project is fully approved, the following obligations are binding on the investigator(s):
Revisions
Any changes in the protocol or consent form are to be approved by the CCHHS IRB before they go
into effect. All changes in key personnel (e.g., co-investigators) are to be reported to the CCHHS IRB.
If an investigator wishes to enroll more participants than the study plan was originally approved for, or
if there is a desire to recruit/enroll participants from a special population not included in the original
protocol, this is considered a revision and must receive IRB approval.
Notification of primary care provider
The investigator must inform the patient's primary care provider of the desire to enter the patient in a
study protocol prior to discussing the project with the patient. The primary care provider’s approval is
not necessary for patient enrollment. However, communication with the primary care provider is
necessary. The participant should also be encouraged to discuss the research study with his/her
primary care provider.
Admitting to hospital or transferring to another hospital or health system
When a patient who is enrolled in clinical research is admitted to the hospital, those involved in his/her
care need to be fully aware of that person's participation in the research, what experimental drugs if
any, the patient is taking, and any expected side effects of those drugs. The investigator is responsible
for ensuring that any other medical provider who will take responsibility for the patient's care is
informed about the patient's research participation and that a copy of the signed consent form is in the
patient's medical record. Of course, if the condition which necessitates hospitalization is judged to be
an adverse event, a report must be filed with the IRB.
When the patient will be transferred to another hospital or health system, the IRB which originally
approved the study must be notified. Appropriate staff of the receiving institution (e.g., attending
physician, nursing supervisor and pharmacist), must be notified that an enrolled patient is being
transferred, and should receive copies of the protocol and signed consent form. A copy of the consent
form must also be put in the patient chart of the receiving institution, and appropriate staff be informed
about how to contact the investigator should the patient experience an adverse event, or if the patient
requires a change in medications or treatment.
Handling experimental drugs
A. If experimental drugs are used, the investigator is responsible for:
 obtaining the necessary participant's consent before the drug is administered;
 insuring that the drug is used under his/her supervision;
 maintaining a proper record of results;
 adhering to the procedure for reporting adverse reactions from a drug or experimental medical
device;
 providing involved personnel with a copy of the approved protocol and other information
related to the drug;
 notifying the Pharmacy Services of who will participate and administer the drug.
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B.
All drugs approved for use in an approved research project must be delivered to, stored in, and
dispensed by Department of Pharmacy. The Drug and Formulary Committee will consider exceptions
to this regulation if submitted to them in writing.
C.
It is the Department of Pharmacy's responsibility to insure drug security, drug control, and
accountability records. The Department of Pharmacy will provide the investigator(s) with the
investigational and/or the control drug labeled for the participant, at the time of administration and in a
form ready to administer.
Consent procedure
Informed consent must be obtained by a licensed physician or other qualified professional listed as an
investigator on the research project. Each participant is to have a copy of individual consent form in
his/her chart written in his/her native language or certified as translated by an individual capable of
such translation. Each participant is to be given a copy of this consent form to keep.
WHEN USING A SHORT FORM CONSENT, THE WITNESS SIGNING THE FORM IS TO
WITNESS THE ORAL EXPLANATION OF THE PROJECT TO THE PROSPECTIVE SUBJECT.
Record keeping
Each investigator is required to maintain accurate, complete, and current records. Each investigator is
required to keep an up-to-date log containing a list of participants entered into a research study. This
record must be made available to the CCHHS IRB at its request for purposes of review.
Data Security - Storage
Paper Documents - Research data containing PHI – Precautions to consider:
1. Paper documents, should be filed in locked file cabinets, under control and watch of the
Principal Investigator.
a. Consider if there is a strong need to transport files; if not, please leave them.
b. Never leave data in an automobile; per IRB policy, if you leave the vehicle, you take the
data.
c. Always know how many files you are transporting. Consider counting the files as you
leave and count again when you arrive at your destination.
d. Always know what you are transporting. Ensure that each file has all the pages at the
destination that it had when you left.
If the paper files containing research data with PHI, or if the computer or other device that houses your
research data with PHI is lost or stolen – please, without delay, contact Corporate Compliance by
calling the 24/7 Hotline: 1-866-489-4949, or email: compliance@cookcountyhhs.org. Please be
sure to leave your name and contact information. In the event that the computer or other device
housing the data is not encrypted, each patient must be contacted, the US Department of Health &
Human Services must be notified, and other regulatory agencies and/or media, in some cases.
Electronic Data Storage - Research data containing PHI can be stored electronically in the following
ways, which meet HIPAA compliance standards:
2. CCHHS assigned network drive, which can be authorized and obtained through CCHHS HIS;
storing data on the network drive allows HIS to protect and backup the data for you. If you
currently do not have access to a network drive, one can be created for you through a request
via the HIS Help Desk (ext. -4HELP).
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
51
Research data containing PHI cannot be stored in the following ways, as they are not acceptable as
secure by CCHHS HIS or considered HIPAA compliant:
1.
2.
3.
4.
5.
CCHHS computer hard drive;
Laptop/tablet hard drive, or flash drive, even if encrypted and password protected;
Dropbox;
Google Solutions;
Box;
If you have authorization to share research data containing PHI, CCHHS has a Business Associate
Agreement (BAA) with Microsoft, therefore research data containing PHI or other sensitive
information can be maintained on Microsoft OneDrive or SharePoint. HIS can assist with these
options as well.
Research personnel qualifications
The investigator(s) must carry out the agreed upon activities and not delegate them to other previously
unspecified staff. Any persons working on a research project on the premises of a Cook County
System affiliate must be properly credentialed with current ID badges.
Publication credit
The Responsible Investigator(s) and associates agree to credit the appropriate CCHHS affiliate in all
publications and presentations deriving from the project.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
52
PROGRESS REPORTS
____________________________________________________________________
Throughout the active life of a CCHHS IRB approved protocol, there is continuing review by the IRB.
The IRB approval on a research protocol is given an expiration date that will not exceed one year form
the approval date. It is the responsibility of the Principal Investigator to submit a progress report on an
approved study, 4 to 6 weeks prior to that expiration date, always using current forms. The “Progress
Report” will summarize the activity of the project for that time period. This continuing review is
intended to monitor unanticipated developments in carrying out the research, whether they be adverse
reactions to the treatment, problems of recruiting or retaining participants, or new findings in the field
of study which may change the risks and benefits involved. It also will monitor the inclusiveness and
success of recruitment into the study by gender and race or ethnicity.
The type and frequency of formal re-reviews by the IRB are related to the risks inherent in the
research. Projects which entail more potential risk, or which involve particularly "vulnerable"
participants may be reviewed more frequently than the required minimum yearly review period.
Investigators must submit a progress report whether the enrollment is ongoing, whether the study is
closed to accrual, but an intervention continues for already enrolled participants, whether there is no
longer an intervention, but participants are being followed and whether the data collection has stopped
and only data analysis continues. Only if the study is complete and all identifiers are removed from the
data, can submittal of progress reports be discontinued.
Correspondence with investigators about each protocol will always have the expiration of approval
date on it. Approval of a modification or addendum does not alter the approval date. It is the
Investigator’s responsibility to submit a progress report about four weeks prior to the anniversary date
of the approval of your project. The IRB office tries to maintain a reminder system but failure to
receive a reminder is not a reason to be tardy with submitting the report. No grace period is allowed
for filing progress reports. Note: IRBManager will have a built in reminder system.
If no progress report has been submitted and approved by the expiration date, approval of the project is
automatically suspended. When a protocol is suspended, all research activity must cease until it has
been reapproved. The only exception is when the PI reports that the abrupt cessation of an
experimental treatment might adversely affect the health of enrolled participants.
When an investigator closes out a study, a final progress report will need to be submitted, so the
CCHHS IRB has an official record of the number of participants enrolled and any results or problems
encountered. Investigators who fail to submit a final progress report may have their future research
approvals delayed until prior final progress reports are submitted. Please notice that the progress report
asks for a differentiation between closed to enrollment, completion of intervention, completion of data
collection, and CLOSED. The form for Progress Reports can be retrieved from the CCHHS intranet or
easily emailed. Upon launch of IRBManager, all forms will be built into that web-based site, kept
current and content can be directly entered.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
53
ADVERSE EVENT DETERMINATION & REPORTING
___________________________________________________________________
One of the most difficult responsibilities in carrying out clinical trials on investigational drugs is the
assessment and reporting of adverse events. An adverse event (AE) is any unfavorable medical
occurrence in a human participant and can be physical, economic, and/or psychological. This includes
any abnormal sign, symptom, or disease whether or not related in part to participation in the research.
If an AE has occurred in one or more participants, you must assess this adverse event to determine if it
is unanticipated. If the AE is unanticipated, then it should be reported. For these purposes
unanticipated has a very specific definition according to the regulations, which is different from its
usual definition.
Unanticipated Events or Events to Report within the Prescribed Timeframe Fulfill the Three
Criteria Below: (see accompanying flow chart)
1. Unexpected;
2. Related or Possibly Related to the Research, and
3. Likely to Place Other Participants at a Greater Risk of Harm.
Definitions:
A. An AE is unexpected when its nature, severity, or frequency is not consistent with known or
foreseeable risks of AEs associated with procedures described in protocol related documents,
labels, or inserts. Expected progression of the underlying condition is not an unexpected event.
B. An AE is related to participation in the research if the AE is caused by procedures involved in
the research. The AE is not related if it is caused by the underlying condition or other
circumstances unrelated to the research or the underlying condition. An AE is possibly related
to the research if there is a reasonable possibility that the AE may have been caused by
procedures of the research.
C. The AE must also place participants at a greater risk of physical or psychological harm in
order to be reportable, which is often a judgment call. If the AE is serious, the participants’
risk of harm is automatically considered increased. Serious AEs are those that result in death,
are life threatening, result in hospitalization, result in persistent or significant
disability/incapacity, result in congenital abnormalities/birth defects, or are based on medical
judgment to be serious. It is better to err on the side of reporting when there is a question.
Required Reporting & Timeframe
If the AE meets the three requirements above, you must report the AE within the timeframe below
through IRBManager. If the AE is determined to not be unanticipated, it need not be reported
promptly. If the AE does not meet the criteria above, keep this record in your file and include this
event in the AE table of your next progress report. The CCHHS Adverse Event and Incident
Reporting Policy should be consulted for reporting incidents (eMERS).
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
54
Prompt reporting is defined as notifying the IRB within 7 days for most internal unanticipated events
(local to CCHHS). Serious internal unanticipated events must be reported to the IRB within 48 hours.
External unanticipated events (outside CCHHS) must be reported within 14 days from the date the
local study staff becomes aware of the event. Fourteen days is also the timeframe for internal events
which were not serious and quickly resolved.
Protocol deviations, may or may not rise to the level of an AE requiring reporting. This will be a
judgment call. Protocol deviations that increase risk should be reported within the timeframe above
(e.g. improper dosing of medication, release of PHI). Protocol deviations with no risk (e.g. performing
a survey or blood draw out of the study window) do not need to be reported promptly unless required
by the sponsor. If not reported promptly, protocol deviations should be reported at the time of the
annual progress report.
When the AE involves Medication Additional Steps are Necessary
Unanticipated Adverse Drug Events (ADE) at the Local Site (Internal)
All unanticipated ADE need to be reported to the sponsor and the CCHHS IRB through IRBManager
if the investigator cannot rule out the investigational agent as a possible cause of the event. ADEs must
also be sent to the CCHHS Director of Quality and CCHHS Risk Management through eMERS. The
CCHHS Adverse Event and Incident Reporting Policy should be consulted for reporting
incidents (eMERS). A life threatening or fatal local ADE must be reported within 48 hours.
In addition to full description of the ADE, the investigator must also provide their determination of
causality with reasoning, assessment of severity, recommendation for monitoring other participants,
and outline revisions to the consent form, and if none, articulate why no changes are needed.
ADE Reports from External Sites
Note: For NIH-sponsored clinical trials the investigator may not receive individual ADE reports from
other sites, but rather a summary report from the study's Data Safety Monitoring Board. Copies of
these summary reports should be forwarded to the IRB.
All DSMB reports must be sent to the IRB with recommendations for monitoring other subjects in the
study in the future. If necessary, revise the consent form to reflect any new information about the ADE
or any additional tests which may be needed. If necessary, verbally inform already-enrolled subjects
about the new ADE; perform any additional tests which may be needed. (The IRB will determine
whether this is necessary). Advise as to the approach taken by the National Study Center based on the
ADE.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
55
Determining Whether an Event Needs to be Reported
Did an adverse event occur in one or more subjects?
(A PHI breach is an adverse event that must always be reported to
Corporate Compliance & CCHHS IRB)
YES
NO
Is the adverse event unexpected in nature, severity, or frequency?
YES
NO
Is the adverse event at least possibly related to this study?
YES
NO
Did the adverse event result in greater risk/harm to participants or others?
YES
This event is reportable to the
CCHHS IRB and must be
submitted in the appropriate
time frame through
IRBManager.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
NO
STOP!
The event does not
need to be reported
immediately. Report
with next progress
report.
56
Scientific Quality Assurance Program
The CCHHS Office of Research & Regulatory Affairs has an established, active program of scientific
quality assurance to ensure high standards in protecting human participants in research. The Scientific
Quality Officer, reporting to the Director of Research & Regulatory Affairs, is assigned to carry out
audits of research studies involving human participants and report back to the IRB on findings. Both
post-approval monitoring and for-cause audits are conducted to evaluate compliance relating to the
conduct of human participant research with federal regulations, state and local laws, and CCHHS
policies and procedures. Audits also serve as a vehicle for continuing education, operational
awareness, and quality improvement.
Post-approval monitoring is a routine compliance review of the study documents and procedures.
Studies are selected for monitoring both randomly and according, but not limited to, the following
criteria: risk level, use of INDs or IDEs, enrollment of vulnerable populations, and requirement of
more than annual review by the IRB. For-cause audits are not routine and are usually triggered by,
but not limited to, the following: participant complaint, employee complaint, whistleblower, new
information that may affect the rights/welfare of research participants.
Audit Procedures
1. Once a study is identified for an audit, the Scientific Quality Officer will contact the Principal
Investigator via email to set up a time and space for the audit to take place. The Principal
Investigator and/or Study Coordinator must make all study documents available at the time of
the audit.
2. Using the CCHHS Audit Worksheet (see appendix for an example), the Scientific Quality
Officer will review some or all aspects of the research records.
3. After the audit, the Scientific Quality Officer will discuss the audit results with the CCHHS
IRB, IRB Chair, and Director of Research & Regulatory Affairs and prepare a post audit report
for the Principal Investigator. If there are no compliance issues, no action is required. If there
are problems or deficiencies, the report will include corrective actions which the Principal
Investigator is expected to respond or comply within the determined time frame.
4. The Principal Investigator will respond to the report in writing detailing what corrective action
plans were or will be taken and when.
5. If the corrective actions are not completed, the Scientific Quality Officer may recommend to
the convened IRB that a suspension be considered for the study that was audited or for studies
that a Principal Investigator is conducting.
CCHHS investigators are urged to consult with the Scientific Quality Officer if there are any questions
about the appropriate procedures and standards to be followed. Investigators, their staff members, and
collaborators are expected to cooperate fully with any site visit or audit carried out as part of the
scientific quality assurance program.
An example of the Scientific Quality Assurance Audit Tool follows this section on the next page.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
57
CCHHS IRB#: ___________________
PI: ______________________________
Criteria
DATE OF AUDIT: ___________________
COORDINATOR: ___________________
Please check appropriate response to the
following questions.
IRB
Documentation
Have all investigators completed IRB training?
Are all IRB records in an accessible location?
 Current Approved Protocol
 Previous Protocol Versions
 Consent Form
 HIPAA Form
 Advertisement/Recruitment Material
 Data Collection Tool
Are the following documents stamped with a
current IRB approval expiration stamp?
 Consent Form
 HIPAA Form
 Advertisement/Recruitment Material
 Data Collection Tool
Is all correspondence to and from the IRB on file
in a binder/folder?
 Application
 Approval Letter
 Continuing Review Approval Letter
 Amendments
Is there documentation of continuing review
submission performed in a timely manner?
 Were there any time lapses noted
 Was subject enrolled during a time
lapse?
If the study has been completed, can the protocol
be closed?
Additional comments:
Informed
Consent
Is the original consent form on file?
Does the consent form on file match the IRB
approved consent?
If changes were made to the consent, were they
submitted and approved by the IRB?
Are all of the consent forms signed and dated by
all required individuals?
 Were IRB stamped versions used?
 Is there a consent form for every subject
enrolled in the study?
 Are research personnel who are
obtaining consent authorized and trained
to do so?
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
Yes
No
N/A
Comments
58
Criteria
Please check appropriate response to the
following questions.
Yes
No
N/A
Comments
Did the subject receive a copy of the signed
consent form?
Is the subject’s receipt of signed consent
documented?
Is the date of the first enrollee after the approval
date?
 If not, was the IRB notified?
If any subject is a minor, was assent obtained? If
not, please explain:
 Verbal assent ages 6-11
 Written assent age 12 and up
If subject was re-consented, is this form available
for review?
If oral consent was used, was the IRB approved
script used to enroll subjects?
Additional comments:
Eligibility
Is there a checklist for the following criteria?
 Inclusion
 Exclusion
 Was inclusion/exclusion appropriate for
the given subject? Explain any protocol
deviations.
Additional comments:
Adverse
Event (AE)
Reporting
Were AE’s adequately reported to IRB since last
review (type, grade, duration, dates)?
 If an AE is unreported, please explain.
Were there any off-site, safety reports?
 Were they reported to the IRB?
Additional comments:
Data
Management/
Documentation
Is subjects’ privacy protected and are safeguards
in place as approved by the IRB?
If data were to be collected anonymously, has
anonymity been maintained in the physical
and/or electronic records?
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
59
Criteria
Please check appropriate response to the
following questions.
Yes
No
N/A
Comments
Are hard copies of consent and data forms
stored in a secure, locked location?
Are electronic data on a secure and protected
computer?
 Are electronic data files password
protected?
 Is access to computer, electronic files,
and physical files limited to appropriate
study personnel?
 Are the raw research data stored and/or
disposed of as described and approved
by the IRB?
Additional comments:
Study
Procedures
Were study procedures implemented as
approved by the IRB?
Were procedures for each subject documented in
study records?
If a procedure was missed, is the reason
accurately documented?
Is there documentation of proper collection,
storage, and handling of all study specimens
and/or study drugs and/or devices?
For research subjects, is there a subject
enrollment log?
Is there a monitoring log?
If so, how often is the site monitored?
Additional comments:
Signature of Auditor: _____________________________________________________
Betty Anna Donoval, JD, MS
Scientific Quality Officer - IRB
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
60
FINANCIAL CONFLICTS IN RESEARCH
Hidden financial stakes in the outcome of a research project have the potential to bias the way research
is carried out or reported. For this reason, most professional journals now require disclosure of such
interests, if they exist, with the publication of scientific articles.
By federal regulation, institutions must also ensure that the design, conduct, or reporting of research
funded under federal grants, cooperative agreements or contracts will not be biased by any conflicting
financial interest of those investigators responsible for the research. The Cook County Health &
Hospitals System has adopted a policy (Section F) requiring that all significant financial interests in a
research project, regardless of its funding source, must be reported. All applications for approval of
research by the CCHHS IRB must include a signed declaration by all investigators as to existence of
any significant financial interest in the research.
All Investigators Must Disclose Significant Financial Interests
An "Investigator" means the Responsible Investigator and any other person who is responsible for the
design, conduct, or reporting of research. For purposes of determining financial interests, the
Investigator's interests include those of his/her spouse and dependent children.
What Constitutes a Significant Financial Interest?
Significant Financial Interest means anything of monetary value, including but not limited to, salary or
other payments for services (e.g., consulting fees or honoraria); equity interests (e.g. stocks, stock
options or other ownership interests); and intellectual property rights (e.g., patents, copyrights and
royalties from such rights).
Financial interests which are subject to reporting for any given research proposal include those which:
Would reasonably appear to be affected by the specific research proposed; and/or are interests
in entities whose financial interests would reasonably appear to be affected by the research.
The term "Significant Financial Interest" does NOT include:





Salary, royalties, or other remuneration from the applicant institution;
Any ownership interests in the institution, if the institution is an applicant under the Small Business
Innovation Research Program;
Income from seminars, lectures, or teaching engagements sponsored by public or nonprofit entities;
Income from service on advisory committees or review panels for public or nonprofit entities;
An equity interest that when aggregated for the Investigator and the Investigator's spouse and
dependent children, meets both of the following tests:
1. Does not exceed $5,000 in value as determined through reference to public prices or other
reasonable measures of fair market value, and
2. does not represent more than a five percent ownership interest in any single entity;
Salary, royalties or other payments that when aggregated for the Investigator and the
Investigator's spouse and dependent children over the next twelve months, are not expected to exceed
$5,000.
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
61
A financial interest also does not include revenues received by your institution in the form of grants,
contracts, or donations for projects for which you are the principal investigator or project director.
If a Significant Financial Interest Exists, What Actions Must be Taken?
Investigators are required to report any significant financial interests at the time of applying for
institutional approval of a research proposal. A box is included next to the investigator's signature
block in Form D-III and in the form in the Supplement to this Guidebook to indicate if a significant
financial interest exists. If there is a significant interest, the Financial Interest Statement form
(retrievable via CCHHS Intranet, email or IRBManager, once launched), must be completed and
submitted with the application for institutional approval.
The CCHHS IRB, as part of the normal protocol review process, consider any reported interests,
determine if there is a potential conflict of interest, and, if so, will determine how to manage, reduce or
eliminate the conflict. If your research project does not require the use of human or vertebrate animal
subjects, submit a copy of the research protocol and the Financial Disclosure Form to the Office of
Research & Regulatory Affairs.
Examples of conditions or restrictions that might be imposed to manage conflicts of interest include,
but are not limited to:
1.
2.
3.
4.
5.
6.
Public disclosure of significant financial interests;
Monitoring of research by independent reviewers;
Modification of the research plan;
Disqualification from participation in all or a portion of the research funded;
Divestiture of significant financial interests; or
Severance of relationships that create actual or potential conflicts.
OTHER RESOURCES AVAILABLE REGARDING HUMAN SUBJECTS
RESEARCH
The Office for Research & Regulatory Affairs (312) 864-0716 or (312) 864-4821 has many other
reference materials available to assist in the preparation of research protocols and the IRB
application process. Please call if you would like to obtain additional materials.
APPENDIX
Important Reference Materials (Online Links):
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
62
1. The Belmont Report: http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html
2. Federalwide Assurance (FWA):
http://www.hhs.gov/ohrp/assurances/assurances/filasurt.html#sectiona
3. HHS policy for the Protection of Human Research Subjects:
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html
4. FDA Regulations Relating to Good Clinical Practice and Clinical Trials:
http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ucm155713.htm#FD
ARegulations
5. NIH Guidance Regarding Social Media Tools
https://www.nih.gov/health-information/nih-clinical-research-trials-you/guidance-regardingsocial-media-tools
6. CCHHS IRB Application and HIPAA Authorization Forms (CCHHS Intranet)
http://cchintranet.cchhs.local/Intranet/Main.aspx?tid=436&mtid=431
7. CCHHS IRBManager Instruction Manual - forthcoming
8. NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving
Human Subjects
https://grants.nih.gov/grants/guide/notice-files/not98-024.html
9. ACOG Committee on Ethics – Policy on Inclusion of Pregnant Women in Research
http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-onEthics/Ethical-Considerations-for-Including-Women-as-Research-Participants
Books/Websites; Historical References – Research abuses; Tuskegee Study:
Medical Apartheid: The Dark History of Experimentation on Black Americans from Colonial Times to
the Present – Harriet A. Washington, Doubleday, 2006
Bad Blood: The Tuskegee Syphilis Experiment – James H. Jones, The Free Press, 1993
The Immortal Life of Henrietta Lacks – Rebecca Skloot, Crown Publishers, 2010
The Spirit Catches You and You Fall Down: A Hmong Child, Her American Doctors and the Collision
of Two Cultures – Anne Fadian, Farrar/Strauss and Giroux, 1997
NIH Office of History – Timeline of Laws Related to the Protection of Human Subjects:
https://history.nih.gov/about/timelines_laws_human.html
APPENDIX – Continued
Books/Websites – Community Based Participatory Research:
CCHHS GUIDANCE - RESEARCH WITH HUMAN PARTICIPANTS 10/2016
63
Physicians Committee for Responsible Medicine - Human Experimentation: An Introduction to the
Ethical issues
http://www.pcrm.org/research/healthcare-professionals/research-compendium/humanexperimentation-an-introduction-to-the
Methods for Community-Based Participatory Research for Health, Barbara A. Israel, Eugenia Eng,
Amy J. Schulz, Edith A. Parker, Jossey-Bass, 2012
Community-Based Participatory Research for Health: From Process to Outcomes, Meredith Minkler &
Nina Wallerstein, Editors; Jossey-Bass, 2008
Community-Based Participatory Research for Health, Meredith Minkler & Nina Wallerstein, Editors;
Jossey-Bass, 2003
The Role of Community-Based Participatory Research, Agency for Healthcare Research and Quality
(AHRQ), http://archive.ahrq.gov/research/cbprrole.htm
Fees for Cook County Health & Hospitals System IRB Review
Issued December 1, 2015; Effective January 1, 2016
CCHHS IRB charges a review fee for industry sponsored research. IRB review fees are not charged for nonprofit sponsored studies supported by the National Institutes of Health (NIH), other government agencies, or
investigator-initiated studies. A onetime fee will be charged for the review of any new industry funded studies
submitted on or after January 1, 2016. There will be no charge for renewals, amendments/modifications,
protocol deviations, unanticipated events involving risk, or final reports.
Rates for IRB Reviews of Industry Sponsored Research (effective 1/1/16)
Type of Review
Initial
Continuing
Amendment
Full
$2,800.00
No Charge
No Charge
Expedited
$1,500.00
No Charge
No Charge
Exempt
$500.00
No Charge
No Charge
Closing
No Charge
No Charge
No Charge
The fees are based on the anticipated costs associated with the protocol review by the IRB and are charged for
services rendered. The fees are due in full even if the IRB does not approve the study, participants are never
enrolled, or the study is terminated before objectives are reached. IRB fees are non-refundable and subject
to change.
The invoicing and collection of fees will be managed by The Hektoen Institute for Medical Research with the
assistance of CCHHS Office of Research Affairs. The IRB fee is to be budgeted as a separate line item in the
contract budget and reimbursed by the sponsor at the time of contract execution. The study specific Hektoen
fund number should be included in the IRB submission.
When a new industry sponsored study is filed with CCHHS IRB, The Hektoen Institute will be notified by
Research Affairs that an invoice was sent to the Principal Investigator. Upon receipt of the invoice, the Principal
Investigator will direct The Hektoen Institute to transfer money from the study’s fund to IRB account #129.
Should you have any questions or require clarification about the collection of the IRB fee, please contact Betty
Donoval (bdonoval@cookcountyhhs.org) in Research Affairs at (312) 864-4821.
Should you have any questions or require clarification about transferring funds from your study fund to our IRB
account, please contact Mariela Romo (marielaromo@hektoen.org) at The Hektoen Institute at (312) 768-6021.
APPENDIX – Continued
Informed Consent Template – Sample (next 6 pages)
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64
This template indicates the basic sections to be covered in your consent in upright bold letters.
Language in italics is “help” and gives you more information about the nature of each section.
Language in “quotes” is an example of the way in which you may offer this information. Do not include
quotation marks in your consent. Sample language is written for situations that occur frequently in
research. Please READ the language and be sure that it is TRUE for your study.
Use Letterhead for first page. Number pages, Use font of at least 12 pt. Aim for 7th grade reading level. Provide
a 2” x 2 3/4” space for an Approval stamp on each page. This consent does NOT include HIPAA
authorization. A separate authorization is required.
Title of Study
Names and affiliation of Investigators should be listed beneath the title.
Introduction
“You are being invited to participate in a research study.
This description of the study is called an ‘informed consent.’ After you learn about the study, you will decide
whether or not you want to participate. You may take this description home and discuss it with your family or
friends to help you decide. There may be words or ideas you do not understand. Please ask questions.
Participation is voluntary. Whether you join the study or not, your medical provider will continue to care for you
as before.”
Purpose of this Research
“This study seeks to answer the question: ----- ” Describe the research question as clearly as possible. You
may want to begin with what is already known. For example: “Study drug is helpful in treating xyz… This
study is asking ‘Is the study drug also able to extend life or the quality of life of patients with ABC health
condition.”
Indicate how many participants will take part in the study within CCHHS and in total.
What to expect
The description should include the duration of the study. Indicate how many visits will take place and how long
each visit will last.
“This is the care you will be getting for your condition, whether you participate in this research or not:”
List any tests and/or procedures. You do not have to go into detail repeating information that will be covered in
a ‘consent to treat.’ The idea is to differentiate the research activities from the routine clinical care procedures.
“These are the additional research procedures or medications that you will have if you join this study:”
List all tests and procedures. Indicate how much time is involved. A chart of what takes place at each visit may
be helpful especially if the same procedures take place repeatedly.
“These are the procedures or medications that you would or might get as part of your normal care for your
condition, that you will not get if you join the study:”
Risks
“These are the risks to you from your regular care for your condition:”
Provide risks of care that would be experienced even if patient did not participate in the research.
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“These are the additional risks to you that may arise from joining this study:”
List risks including inconveniences using lay language. It is helpful to indicate how frequently they occur (what
percentage of patients). If the significance of the side effect is not clear, you should explain it. Distinguish
between routine care and research where appropriate.
Confidentiality
“Your research records will be kept private. The CCHHS (name collaborating Institutions if relevant) study
team will have access to these records. In addition, your records may be reviewed by the study sponsor, xyz,
regulatory agencies such as the Food and Drug Administration (include only if this is the case) and the Cook
County Health & Hospitals System Institutional Review Board (IRB) or as required by law. The IRB is a panel
whose job is to review the ethics of research.”
If you are releasing PHI to an outside coordinating center, say this and get permission.
“Researchers at Stroger will send parts of your medical record by a secure encrypted method to the xyz group
which is located in (state). The information from your records will be given a code number before it is sent.
Only the Stroger research team will have the key to link your code number to your name. (Say this only if it is
true, correct it if it is not accurate). If the xyz group releases your data to anyone else, the recipient will not
have any identifiers either, only the code number. A separate HIPAA authorization describes this in more
detail.”
If the data do not include any of the 18 HIPAA identifiers, this is not necessary.
Benefits
List possible benefits. Do not include compensation for expenses in benefits. If there are none, indicate that
there are no direct benefits to the participant but that this study may help to improve treatment in the future e.g.
“Although we do not know whether the study drug will be effective, this research will help us to treat patients
with your condition in the future”
Alternative to participation
Briefly describe treatment options. If this is not a therapeutic study indicate that the alternative is to choose not
to participate. Indicate that if new information or treatments become available which may affect the decision to
participate, you will notify the participant. And then you must do this. This includes information about newly
approved treatments for the participant’s condition.
Costs and compensation
Describe how the research is paid. You may include something like “Your regular care that is not part of this
research will be paid for in the way in which your care at Stroger is normally paid.” If participants are being
reimbursed, you must include this, for example, “You will be receive ($30) for each study visit to help pay for
travel and child care expenses”
Injuries or complications
”In the unlikely event of a research related injury, you will receive medical care but the care will be paid for in
the same way in which your routine care is paid for at County. There is no special fund to pay for injuries.”
Or - “In the unlikely event of a research related injury, you will receive medical care which will be paid for by
the sponsor. The sponsor will pay only for medical expenses and will not pay for lost wages or other nonmedical costs.”
And, in either case - “You are not being asked to give up your legal rights by agreeing to these conditions”
Leaving the study
“You may leave this study at any time. In order to make sure that you understand the consequences of leaving
the study and your options, the study doctor may want to discuss your decision to leave the study with you, but
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the decision to leave is yours alone. Your study doctor may remove you from the study for a variety of reasons
(including a determination that the study is not what is best for you or instructions from the study sponsor to do
so).”
“If you leave the study without withdrawing your permission to continue to collect and/or use of your medical
information, your medical information may continue to be used for this research. If you wish to stop
researchers from using your medical information, you must say so in writing. How to withdraw your permission
to use your medical information is described in the HIPAA authorization.”
People you may call
“If you have questions about this research study, call Dr. Cook at (123) 456-7890” (Name and number- use a
number that can be reached. The IRB may test this number)
“If you feel you a suffered a research injury, call name and number” – (use a number that can be reached.
The IRB may test this number).
“If you have questions about your rights as a research participant, call the Cook County Health & Hospitals
System Institutional Review Board at 312 864-4821 during regular business hours. You may leave a message.
Your call will be treated confidentially “
Signatures
“I have explained all aspects of this research and have answered the participant’s questions.”
Person Obtaining Consent
Signature Person Obtaining Consent
Date
Date
“I have had my questions answered, I understand that my participation is voluntary and I agree to participate in
this study”
Participant
Date
Signature of Participant
Date
SPECIAL additions
Tissue storage:
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“In this study tissue samples will be stored for additional research. You may agree to having your (left over)
tissue used for (re-word appropriately)
Research on your condition, Initial if OK __________
Research on other conditions. Initial if OK __________
Research that identifies genetic characteristics that may make a person prone to disease or responsive to
treatment.
Initial if OK __________
Results from these additionally studies would not benefit you in anyway. The information will not be put in your
medical record or shared with your provider. The tissue sample that is sent to a central repository will be
identified by a code rather than your name or medical record number, however, this code number could be
linked back to your name.”
“I agree to participate in the tissue study.”
Signature of Participant
Date
Affidavit of Interpreter
If the subject does not understand English, the subject should still sign the English consent however the
Interpreter should sign the affidavit.
“I have translated this consent for the participant and have translated his/her questions to the investigator and
have translated the answers back to the participant.”
Printed Name of Interpreter
Signature of Interpreter
Detainees
“I understand that choosing to participate in this study will not help my status in judicial system in any way and
refusing to participate will not be held against me. This study will not affect my sentence, parole or prison
conditions.”
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Pregnancy
“As described above, you should not become pregnant during this study. If you do become pregnant during this
study, you will no longer be given the study drug. Your pregnancy will be cared for through another
department, however with your permission, your pregnancy and baby will be followed by the research study”
Questionnaires
“Completing the survey questionnaire will take about n minutes. The survey will not contain your name but the
code number will be linked to you. (if true). The questions are about xyz. Answering them may make you feel
(sad, uncomfortable –if true). You may skip any question you do not want to answer.”
Focus Group
“Confidentiality in focus groups depends on the participants. You will not use your name in the group.
Participants will be reminded not to repeat anything in the group but there is no way to be sure that they will
follow this direction or that you may not know someone in the group.”
Minors
Typically minors under 7 do not assent. (However, except in the case of therapeutic studies, their resistance
excludes them from participation). Minors between 7 and 13 should sign a simplified version of the consent.
Minors over 13 may sign the consent on a line for assent because the language in the general consent should be
at a 7th grade level. The consent for parents and guardian should use appropriate pronouns such as “your child”.
“You/your child” is almost never acceptable. When minors turn 18, they must be re-consented.
Wards of the state
In general, the IRB approves only 45CFR46.404, or 405 research. In the rare case in which 406 research is
approved, Wards of the State are not to be included.
Decisionally Impaired
A legally authorized representative may consent for persons who may not be able to consent due to mental
retardation, extreme pain or anesthesia, or mental illness (mental illness does not automatically preclude the
ability to consent). If a legal representative is used, language should be appropriate (“Your family member”)
New information relevant to choosing to participate
Where appropriate, promise to keep the participant informed about new developments that might affect the
decision to participate. The promise must then be kept.
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Persons to help locate participant lost to follow-up
If you wish to identify contacts to locate lost participants, you must have permission. You must tell the
participant how the person will be contacted and exactly what you will tell that person. Remember that
mentioning the hospital or jail, may not be desirable and may cause alarm.
“We would like the names and contact information of a friend or relative you say we may contact, if we are do
not know how to find you. If we cannot contact you, we will try contacting the person (by phone, letter say
how) and say:
‘This is Mr. X from the Healthy-Walks project. Mr. Smith gave us your name to help locate him when he joined
our program last year. Do you know how we can contact Mr. Smith’?
If it ok with you to try to locate you in this way, please provide the information requested below
Name of contact __________________________________________________________
Address of contact_________________________________________________________
Phone number of contact ___________________________________________________
Relationship to contact _____________________________________________________
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APPENDIX – continued
MS Word Readability Tools
1.
2.
3.
Click the File tab, and then click Options.
Click Proofing.
When correcting spelling and grammar in Word, make sure the Check grammar with spelling check box is
selected.
4. Select Show readability statistics.
After you enable this feature, open a file that you want to check, and check the spelling. When Outlook or Word
finishes checking the spelling and grammar, it displays information about the reading level of the document.
Understand readability scores
Each readability test bases its rating on the average number of syllables per word and words per sentence. The
following sections explain how each test scores your file's readability.
Flesch Reading Ease test
This test rates text on a 100-point scale. The higher the score, the easier it is to understand the document. For most
standard files, you want the score to be between 60 and 70.
The formula for the Flesch Reading Ease score is: 206.835 – (1.015 x ASL) – (84.6 x ASW)
Where:
ASL = average sentence length (the number of words divided by the number of sentences)
ASW = average number of syllables per word (the number of syllables divided by the number of words)
Flesch-Kincaid Grade Level test
This test rates text on a U.S. school grade level. For example, a score of 8.0 means that an eighth grader can
understand the document. For most documents, aim for a score of approximately 7.0 to 8.0.
The formula for the Flesch-Kincaid Grade Level score is: (.39 x ASL) + (11.8 x ASW) – 15.59
Where:
ASL = average sentence length (the number of words divided by the number of sentences)
ASW = average number of syllables per word (the number of syllables divided by the number of words)
Understand how languages affect readability scores
The languages that you use in a document can affect how your Office program checks and presents readability
scores.

If you set up Word to check the spelling and grammar of text in other languages, and a document contains
text in multiple languages, Word displays readability statistics for text in the last language that was
checked. For example, if a document contains three paragraphs — the first in English, the second in French,
and the third in English — Word displays readability statistics for the English text only.

For some European languages within an English document, Word displays only information about counts
and averages, not readability.
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