Cook County Bureau of Health Services Institutional Review ...
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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 Page 63
Regulatory Reference Links; Books/Websites
IRB Review Fee Structure (for Industry Sponsored Research)
Informed Consent Template and Sample Language
MS Word Readability Tools
INTRODUCTION - RESEARCH ETHICS WITHIN CCHHS
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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.
HUMAN RESEARCH: ETHICAL FOUNDATIONS
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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.
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 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 INSTITUTIONAL REVIEW BOARD (IRB) OVERVIEW
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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 |Oversees research at: |Contacts: |
|Cook County Health & Hospitals |John H Stroger, Jr. Hospital of Cook County |Mildred Williamson, PhD, MSW Director |
|System |Cermak Health Services - Cook County Jail and |mwilliamson@, |
| |Cook County Juvenile Temporary Detention Center |312-864-0716 |
|Office of Research & Regulatory|Cook County Department of Public Health |Betty Donoval, JD, MS Scientific Officer |
|Affairs |Ambulatory & Community Health Network (ACHN) |bdonoval@, |
|(Manages CCHHS IRB) |Oak Forest Health Center |312-864-4821 |
| |The Ruth M Rothstein CORE Center |Audrey French, MD CCHHS IRB Chair |
|Located in: |Provident Hospital of Cook County |afrench@, |
|Hektoen Building | |312-864-4578 |
|627 S Wood Room 333 | |Romina Kee, MD CCHHS IRB Vice Chair |
|Chicago IL 60612 | |312-864-3630 rkee@ |
|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. |
Membership and structure of the IRB
Composition
IRB membership is comprised of scientists, nonscientists, and local community members (non-affiliated). 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.
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.
a. Maintain current educational activities reflective of the duties and roles of the IRB.
b. Represents the IRB in discussions with other segments of the organization including researchers.
c. Together, with the Director of Research and Regulatory Affairs represents the organization in discussions with federal authorities.
d. Review protocols and determine the level of review required based on risk assessment for expedited or full review.
e. 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.).
f. Directs the proceedings and discussion of the meetings for focus on issues pertinent to the IRB roles and responsibilities.
g. Is a voting member of the CCBHS IRB.
h. Review and make decisions concerning responses to conditions for IRB approval. The Chair may delegate this activity to the IRB Administrative Staff.
i. Delegate expedited reviews to IRB members for review.
j. Review Requests for Modification and determine level of review required based on risk determination.
k. 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.
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.
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.
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@, 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.
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.
APPROVAL OF RESEARCH PROTOCOLS
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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.
(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.
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);
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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) 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 multi-site 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.
CENTRAL IRB GUIDELINES FOR REVIEW, DOCUMENTATION AND APPROVAL
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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.
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.
EXEMPTION FROM REVIEW
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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. |
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.
USE OF INVESTIGATIONAL DRUGS OR DEVICES OUTSIDE CONTROLLED CLINICAL TRIALS
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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.
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.
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.
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.
GENERAL REQUIREMENTS FOR INFORMED CONSENT/HIPAA
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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: |
|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. |
|A description of the expected risks or discomforts to the participant. |
|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. |
|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. |
|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. |
| |
| |
|ADDITIONAL CONSENT REQUIREMENTS |
|When required by the IRB, one or more of the following additional elements are provided to each participant: |
|A statement that a procedure may involve unforeseeable risks. |
|A description of circumstances under which the participant's participation may be terminated by the investigator without the |
|participant's consent. |
|Additional costs to the person resulting from participation in the research. |
|The consequences of the participant's decision to withdraw from the research. |
|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 e-mail. 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.
EXCEPTIONS FROM CONSENT REQUIREMENTS
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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.
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 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.
INFORMED CONSENT FOR SPECIAL PARTICIPANT CLASSES
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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 life-threatening 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 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
(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.
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.
GUIDELINES FOR OBTAINING INFORMED CONSENT
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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 non-compliant 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 non-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 eighth-grade 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 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.
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) 864-4821.
FORGOING PARENTAL CONSENT IN RESEARCH WITH MINORS
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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 ( ................
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