1. How do you define "Research" and "Human Participant"?
- Under DHHS regulations: Any systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge;
- Under FDA regulations: Any experiment that involves a test article and one or more human subjects.
- Under DHHS regulations: An individual about whom an investigator who is conducting research obtains: (1) data through intervention or interaction with the individual, or (2) identifiable private information;
- Under FDA regulations: An individual who is or becomes a participant in research, either as a recipient of the test article or as a control; includes human specimens on which an investigational device is used.
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2. Does the DUC or IRB need to look at this project?
Cottage Health System uses the following two convened groups to review research and data requests:
- Data Use Committee (DUC): An institutional committee designed to review requests for data and protected health information (PHI) in order to maintain compliance with the HIPAA Privacy and Security Rules. By routing a Pre-Assessment Tool (PAT) through upper management, institutional suitability can be assessed, as well as the type of support required. The DUC works in conjunction with, and on behalf of, the IRB on regulatory matters involving HIPAA and research exemptions. If the data request does not meet the definition of research, it will only need review by the DUC via the Pre-Assessment Tool (PAT) document (no IRB review).
- Institutional Review Board (IRB): A federally-mandated Board designed to review, approve, and monitor human subjects research. No research may commence without IRB approval.
All eligible projects being conducted by staff at, or utilizing the facilities of, Cottage Health System must be submitted to the either the DUC or the IRB to ensure compliance with Federal regulations and institutional policies.
A CHS Research Review Flow Chart is available here.
To review the Federal decision charts go to the Office for Human Research Protections (OHRP) website, http://www.hhs.gov/ohrp/, or go directly to the charts at http://www.hhs.gov/ohrp/humansubjects/guidance/decisioncharts.htm#c1. These graphic aids are intended to assist in the decision-making process to determine the review requirements for a particular activity. Several decision charts are available to address a variety of questions, including:
- Chart 1) Is an Activity Research Involving Human Subjects?
- Chart 2) Is the Human Subjects Research Eligible for Exemption (and if so, does a particular exemption apply)?
- Chart 8) May the IRB Review Be Done by Expedited Procedures?
To find out if anything is needed for your project to meet federal, state and institutional guidelines, call the Research Compliance department office to arrange a discussion with someone in the department.
In most cases, protocols which have been reviewed and approved by another institution's IRB must still be reviewed and approved by Cottage Health System IRB. This is to ensure that all of the operational issues and institutional approvals have been met.
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3. To whom do I submit my project?
Data Use Committee (DUC) pre-assessment tools should be submitted to:
Tamara Norton, MHS, CIP
682-7111 ext. 53336
Clinical Trial and sponsored research queries should be submitted to:
Betsy Lazarine, PhD
Following DUC approval, IRB preview documents should be submitted to:
Leilani Price, PhD, CIP
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4. Are other approvals required?
This process begins with submission of a pre-assessment tool (PAT) to the Data Use Committee (DUC). If a project is not supported by a department for reasons other than scientific merit, the IRB will not review the project: The decision to proceed with a project will be made at the departmental and/or institutional level. All research proposals must have the approval of the department director and, if applicable, the CHS Institutional Official in order to be eligible for IRB consideration. These individuals review research proposals to determine the appropriateness of the research to the institution's objectives.
If you are participating in a sponsored clinical trial, you must contact the Research Administrator regarding institutional negotiation of the Clinical Trial Agreement (study contract).
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5. Should a QI / QA project be presented to the DUC?
Quality assessment (QA) projects involve the evaluation of institutional programs and services. QA activities are part of the normal functioning of a department and as such do not require DUC review.
In comparison, quality improvement (QI) projects utilize the findings from a QA evaluation in order to make positive changes to enhance the service. Quality improvement is considered a health care operation under the HIPAA Privacy Rule, and as such is generally exempt from the HIPAA requirement regarding authorization to use or disclose protected health information (PHI). The DUC would like to review QI projects prior to implementation, in order to ensure that such projects do indeed qualify as QI and that no other HIPAA or institutional/operational considerations are recommended. QI activities and research can be very similar and it may be difficult to distinguish one activity from the other. In fact, merely making one or two changes can convert QI to research or vice versa. The DUC will assist you with this determination.
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6. What is the difference between Full Board, expedited, and exempt review?
Full Board IRB Review means the research is reviewed by the IRB at a convened meeting under strict Federal guidelines. Full Board IRB review is required for virtually all new research protocols; and is definitely required for research involving more than minimal risk, such as research involving invasive procedures, investigational drugs and devices, multiple blood sample collections, or research that involves vulnerable populations including subjects under 18 years of age, pregnant subjects, or special classes of at-risk populations.
The IRB meets on the 3rd Wednesday of each month at 12:15. The deadline for new study applications is the 4th Wednesday of every month to be considered for the full Board meeting.
A preview process is available for the consent form and the IRB 10 Items. These documents must be received no later than the 3rd Wednesday of the month and must be submitted via email as Word documents to a member of the Research Compliance department. Necessary corrections and/or changes to either of the documents will be communicated back to the investigator/study coordinator via email. When corrections have been made, the investigator/study coordinator shall submit the original IRB application no later than noon on the 4th Wednesday of the month. The principal investigator (or upon prior IRB approval, a co-investigator) must attend the IRB meeting to respond to questions from the members. Voting is held in closed session.
Expedited Review means the activity may be reviewed by one or more designated IRB members, but convened board review is not required. Although new studies are almost always reviewed by the Full Board, those that qualify for expedited review will usually be allowed to undergo continuing review by expedited review. To qualify for expedited review the research must present no more than minimal risk to human subjects and involve only non-invasive procedures. Federally funded or regulated research must meet one of the specific categories of activities identified in the regulations as eligible for expedited review.
Expedited Review of research will normally be carried out by the Chairperson and an IRB department staff member. Federal regulations do not allow for the disapproval of research through the expedited review process. Therefore, if a research project or change in a project is not considered approvable by the expedited reviewer(s), the item will be scheduled for Full Board review at the next available meeting.
Exempt Review means that the activity may be reviewed by one or more designated IRB members to determine if the research project qualifies for exempt status. Research activities that qualify for exemption are exempt from compliance with the Federal regulations governing research or further reporting to the IRB. To qualify for exempt status the research must have little, if any, associated risk. Initial exempt determination shall be made by the DUC, followed by review by the IRB Chair. If the IRB Chair concurs, s/he will provide the investigator with an IRB exemption letter.
Investigator's conducting research exempt from IRB review are required to follow the ethical principles found in the Belmont Report and to comply with HIPAA regulations. If an investigator is using Protected Health Information (PHI), the investigator must also be granted a waiver of authorization by the IRB (see IRB policy #8012.11 IRB Standards for Privacy and Security of Protected Health Information). If the waiver criteria cannot be met, the investigator must obtain authorization from subjects. The DUC will have final authority regarding PHI use.
Examples of exempt research activities include research involving the study of existing data, records, or specimens if the sources are publicly available or if the information is recorded so that subjects cannot be linked directly or through identifiers. It also includes surveys, observations of public behavior, taste and food quality evaluations (see also #2 above for the link to the OHRP Decision Charts).
Following PAT assessment by the DUC, if the research is deemed to be exempt, the requirement to complete a formal IRB application will be waived. However, additional supporting documentation may be requested, as needed.
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7. What is the deadline for submitting new protocols?
New research applications are reviewed at convened meetings held the 3rd Wednesday of each month. Applications are due in the IRB Office three weeks before a specific meeting (the 4th Wednesday of the month). You may request a current IRB Submission Deadlines and Meeting Schedule. A preview process is available for the consent form and IRB 10 Items (see also #6 above, Full Board Review).
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8. Are there fees for IRB review?
An IRB Fee is assessed to support the activities of the IRB Office. The fee is based on the type of study and the type of IRB Review required (e.g. initial review or continuing review). For a fee schedule and additional details, see policy #8012.03, Billing for IRB Review of Research on the IRB website.
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9. What if my project is not approved?
If the IRB disapproves a project, the investigator will receive written notification which will include a statement of the reasons for its decision. The investigator will be given the opportunity to respond (appeal) in person or in writing. No institutional official or committee may approve a research activity that has been disapproved by the IRB.
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10. Who is required to complete the tutorial on human subjects protection?
In order to participate in the conduct of research, all investigators and key research personnel* must complete a basic tutorial course and meet the continuing education requirements every three years.
Proposed research will not be approved until the basic or continuing education requirements are met.
The IRB Office will provide you with the tutorial if you need to take it.
*Key research personnel include those who are involved in the design and/or conduct of the research, have access to human participants, and/or confidential and identifying information, including principal investigators, co-investigators (sub-investigators), research nurses, study coordinators, associates/assistants, students and other support staff or persons assisting with the research.
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11. What must I report to the IRB while my study is active?
The following changes to a research project must be submitted to the IRB for approval prior to the initiation of the change:
- Adverse events meeting the IRB reporting criteria (on-site AEs must be reported within 10 days of the investigator’s knowledge of the event; within 24 hours if the AE is fatal). (See IRB policy #8012.02, Adverse Event Reporting)
- Proposed changes or additions to the research activity
- Any proposed increase in the total number of subjects
- Modifications in subject selection/recruitment procedures and documents (eg advertisements)
- Addition of co-investigators or change of principal investigator
- Addition of research sites
- Incentives (payments to participants)
- Changes to the informed consent form or informed consent process
- Changes to data collection documents that are subject to IRB approval
- Any planned protocol changes, as well as unplanned protocol deviations and violations
- Communications from the study sponsor, monitor, DSMB, or federal agencies overseeing the study
- New findings
Changes may NOT be initiated without IRB review and approval, except where necessary to eliminate apparent immediate hazards to subjects.
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12. How long must I keep my records?
Investigators are responsible for maintaining study-related correspondence, treatment and patient records, copies of signed consent forms for each subject, and copies of case report forms on file for a period of six years past the date the project is officially terminated with the IRB. A copy of the consent form must also be filed in the patient's medical record if any of the tests/procedures/interventions or their results, that are a part of the study protocol, could in any way affect the care of the patient. If, for any reason, an investigator withdraws from the responsibility for maintaining the study records, custody of the records may be transferred to another person. The IRB should be notified in writing of any such transfer.
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13. How does the IRB ensure compliance?
As a requirement of our institutional Federal Wide Assurance with the Office Human Research Protections (OHRP) and to maintain compliance with FDA guidelines, the IRB Office conducts audits designed to assure that both investigators and the IRB are in compliance with federal as well as institutional requirements for the protection of human subjects.
In addition, because our IRB reviews and approves research involving investigational drugs and devices, the FDA conducts audits of IRB records and procedures at least every five years. The purpose of these audits is to identify, report, and correct any deficiencies and/or material breaches in uniformly protecting the rights and welfare of human subjects.
Any research subject, staff member, or member of the community may make a complaint regarding a failure to comply with federal or institutional policy regarding the protection of human research subjects. Examples include, but are not limited to, failure to submit a protocol for IRB review and approval, failure to obtain written informed consent, coercion of a subject, or protocol changes that are not necessarily in the best interest of the patient. The confidentiality of all involved parties will be protected to the greatest extent possible. If the complaint fits within the definition of non-compliance, a non-compliance report shall be initiated.
Investigator non-compliance is defined as non-compliance with Federal, State, or institutional policies which could jeopardize the rights and welfare of subjects. Instances may be identified through institutional audit, during a FDA audit, during normal review process; or by the investigator, other staff, the media, or research subjects. The IRB has written procedures for conducting review of non-compliance issues. These procedures differ depending on the extent of the non-compliance, and in all cases, include an appeal option. For details, see policy # 8012.18 IRB Action Plan for Investigator Non-Compliance on the IRB website.
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14. Are reviews of my ongoing research conducted?
Yes. Federal regulations stipulate that IRBs shall conduct continuing review of research at intervals appropriate to the degree of risk, but not less than once per year. The IRB will determine the frequency and extent of continuing review needed for each study depending on the nature of the study, the degree of risk involved, and the subject population. A continuing review report will be requested from the investigator at intervals determined by the IRB. Failure to submit a continuing review application by the deadline will result in expiration of the study and the requirement to halt ALL study activities. Engagement of research activities after a study has expired constitutes investigator non-compliance and requires notification of sponsoring and/or regulating agencies.
The IRB uses the same criteria when conducting continuing reviews as it uses when initially reviewing and approving the research. During these reviews, the IRB will consider whether:
- the actual risks and benefits are as anticipated;
- any subjects have been seriously harmed and whether the IRB has been informed of any unforeseen problems or accidents that have occurred;
- there are any new findings or adverse events that should be communicated to subjects;
- the procedures agreed upon at the beginning of the research are still being used;
- information contained in the consent document is still accurate and complete;
- IRB approval should be continued.
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15. How do I close my study?
For full Board and expedited studies being notified of continuing review, please complete the Progress Report Form indicating that you wish to close your study.
Please note: You must continue providing continuing review submissions on your research until ALL data analysis is completed. A continuing review of a study in this phase will receive expedited review.
For exempt studies, and all studies wishing to be closed throughout the year (other than at continuing review), please submit a letter explaining that study activities have been completed and a statement that the investigator has closed the protocol.
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16. What about an emergency use situation?
Regulations do not limit the authority of a physician to provide emergency medical care. However, whenever emergency care is initiated without prior IRB review and approval, the patient may not be considered to be a research subject. Such emergency care may not be claimed as research, and the outcome of such care may not be included in any report of a research activity.
The Food and Drug Administration (FDA) defines the emergency use of an investigational drug as the use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval. Emergency use of an investigational drug or biologic product may be exempt from prior IRB review provided that such emergency use is reported to the IRB within five working days. Any subsequent use of the investigational product at the institution is subject to IRB review prior to it's use. Written informed consent is required unless certification of several existing circumstances is documented by both the investigator and a physician who is not involved in the clinical investigation. See policy #8012.08 Emergency Use of a Test Article on the IRB web site, or see the FDA information sheet entitled "Emergency Use of an Investigational Drug or Biologic" which details documentation requirements.
An unapproved medical device is defined by the FDA as a device that is utilized for a purpose, condition, or use for which the device requires, but does not have, an approved application for pre-market approval or an approved application for an Investigational Device Exemption (IDE). An emergency need to use an unapproved device may occur when an IDE for the device does not exist, when a physician wants to use the device in a way not approved under the IDE, or when a physician or institution is not approved under the IDE. The FDA recognizes that emergencies arise where an unapproved device offers the only alternative for saving the life of a dying patient, but an IDE has not yet been approved for the device or the use, or an IDE has been approved but the physician who wishes to use the device is not an investigator under the IDE. The FDA will not object if a physician chooses to use an unapproved device in such an emergency, provided that the physician later justifies to the FDA that an emergency actually existed. The FDA has defined which conditions should exist for a situation to be considered an emergency, and the FDA expects the physician to follow certain patient protection procedures, including but not limited to IRB Chairperson concurrence and the use of a written consent form. See the FDA information sheet entitled "Emergency Use of Unapproved Medical Devices" which details documentation requirements. After use of an unapproved device, in addition to reporting required to the FDA and sponsor, institutional policy requires the investigator to notify the IRB of the emergency use including a written summary of the conditions constituting the emergency within five working days of its use. No subsequent emergency use of the device will be allowed without prior approval by the IRB. For more information see the IRB's policy #8012.23 IRB Guidelines for the Use of Investigational Medical Devices and Humanitarian Use Devices, and policy #8012.08 Emergency Use of a Test Article.
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17. What is the difference between emergency use and compassionate use?
While the term emergency use refers to the immediate need for an investigational agent to be used in a person with a life threatening situation, compassionate use refers to the use of investigational agents in patients who would otherwise not qualify for enrollment into a clinical trial or who are otherwise not eligible to participate in existing research trials.
Although the two terms are often misused interchangeably, they refer to very different courses of action and require completely different IRB review.
Most notably, although emergency use can commence immediately, with a five day grace period of IRB notification, compassionate use requires the prospective full Board review and approval of the requested use before the patient can be treated. Compassionate Use is a special type of research activity and therefore mirrors the requirements of a typical research study: It requires a principal investigator, a protocol, permission and distribution of the agent by the manufacturer/sponsor, informed consent from the patient, and full oversight by the IRB. Sponsors may already have a compassionate use protocol available for patients not meeting inclusion criteria to their active clinical trial(s). If not, each compassionate use case needs submission of an application and approval by the FDA prior to IRB review. In these situations, it is the investigator’s responsibility to apply to the FDA for approval.
See IRB policy #8012.19 Guidelines for the Compassionate Use of Investigational Agents.
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