1. Research - A systemic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. 
2. Human Subject - A living individual about whom an investigator obtains data through intervention or interaction with the individual, or identifiable private information.
3. Minimal Risk - 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.

1. The research is sponsored by this institution, or
2. The research is conducted by or under the direction of an individual in connection with his/her institutional responsibilities, or
3. The research is conducted by or under the direction of an individual who is receiving remuneration from the institution, or
4. The research is conducted by or under the direction of an individual using any property or facility of this institution, or
5. The research involves the use of this institution's non-public information to identify or contact human research subjects for prospective subjects, or
6. The institution's name is used in any way in connection with the study including procurement of sponsorship, announcement or advertisement or other recruitment of subjects.

1.  Full time faculty can serve as principal investigators and mentors.
2. Faculty, who do not meet the qualifications stated above, can serve as co-investigators but not as principal investigators.  In unique situations, the Provost, may waive this constraint provided a mentor is added to the study.
3. MUSC trainees in good academic standing can function as principal investigators with the inclusion of a faculty mentor.
4. MUSC employees can function as principal investigators with the inclusion of a faculty mentor.
5. A principal investigator and the mentor are both responsible for the conduct of the human research.  These responsibilities are outlined in the IRB documents signed by the principal investigator and mentor.

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Employees as research subjects:
Employees (normal volunteers) may not participate in immediate supervisor's studies if the study poses greater than minimal risk.  Exceptions are allowed for those who may derive direct health benefits (e.g. cancer protocol).

1. Student studies can be performed at the VA provided that:
2. The student's mentor is the PI or record at the VA,
3. The mentor has VA privileges, and
4. The student's name is in the informed consent as a PI.

1. Unanticipated problems involving risks to subjects or others;
2. Serious or continuing noncompliance with federal regulations or IRB requirements, and
4. Suspension or termination of IRB approval.

1. Ensure that subjects are adequately informed of the nature of the study;
2. Ensure that subjects' participation is voluntary;
3. Ensure that the benefits of a study outweigh its risks;
4. Ensure that the risks and benefits of the study are evenly distributed among the possible subject population; and,
5. Suspend human subjects activity that violates regulations, policies, procedures, or an approved protocol, and report such violation and suspension the Institutional Official.
6. The IRB(s) will review, and have the authority to approve, require modification in, or disapprove all research activities, including proposed changes in previously approved human subject research. 
7. The IRB will conduct initial and continuing review (not less than once per year), approving research, and reporting IRB findings to the investigator and the Institution.
8. The IRB will determine which projects require review more often than annually and which projects need verification from sources other than the investigator that no material changes have occurred since the previous IRB review.
9. The IRB will ensure that changes in approved research protocols are reported promptly and are not initiated without IRB review and approval, except when necessary to eliminate apparent immediate hazards to the subject.
10. Where appropriate the IRB will determine that adequate additional protections are ensured for vulnerable populations as required by Subparts B, C, and D of 45 CFR 46.
11. The IRB will forward to the Office of Human Research Protections (OHRP) any significant or material finding or action, at least to include the following:
    1. Unanticipated problems involving risks to subjects or others;
    2. Serious or continuing noncompliance with federal regulations or IRB requirements, and
    3. Suspension or termination of IRB approval.

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1. Chair; Vice-chair(s)
2. Men and Women from different ethnicities
3. Non-scientific members
4. Members with experience in patient care from the various colleges and divisions within those colleges
5. Members to represent the interests of children, pregnant women and persons with disabilities
6. Persons not affiliated with MUSC.  These members include but are not limited to attorneys, members of the clergy, and educators representing the local community
7. Members may satisfy more than one of the above categories

1. Preside at meetings of the IRB.
2. Call special meetings when necessary.
3. Advise investigators.
4. Recommend committee members for appointment to IRB.
5. Make decisions in emergency situations to protect subjects and remain in compliance with regulations.
6. Inform IRB and University Officials of developing problems.
7. Appoint Vice-chair(s).
8. Appoint subcommittees of IRB.
9. Relate concerns of IRB staff and members to administration regarding issues in human research review.
10. Liaison with the University Committees.

1. Preside at meetings of the IRB in Chair's absence.
2. Assist the Chair with review procedures.
3. Chair Subcommittees.
4. Other duties in Chair's absence.
5. Act as Chair's designee as required.

1. Attend meetings (or find alternate) and plan to be present for the entire meeting.
2. Contact IRB Office if unable to review for a meeting and find their replacement from the alternate reviewer list.
3. Review all material provided.
4. Contact investigators as necessary.
5. Present primary reviewed protocols to the Board as requested.
6. Do not review or vote on any issue in which there is a conflict, or perceived conflict of interest.
7. Participate in subcommittee activities.
8. Protect confidentiality of records provided.
9. Act as Chair's designee as required.

1. Review IRB submissions and keep IRB members aware of current regulations.
2. Prepare agenda and attend meetings of the IRB.
3. Prepare Minutes.
4. Liaison between IRB members and investigators.
5. Maintain IRB records: IRB discussions, protocols, modifications, correspondence,
6. approvals, continuing reviews, terminations.
7. Advise investigators and study coordinators.
8. Provide continuing education for IRB members, investigators and study
9. coordinators.
10. Attend at least one National meeting for continuing education.
11. Prepare reports as required by regulations.
12. Keep abreast of changes in regulations and communicate changes to investigators.

1. Principal Investigators, Co-investigators, or investigators identified on any human subjects research protocol (which includes faculty, collaborators, consultants, post-docs, house staff, fellows, technicians or others who will play a substantial role in the human subjects research, including a major authorship role when work is reported)
2. individuals responsible for obtaining informed consent
3. research study coordinators and full-time research nurses
4. first year graduate students
5. Deans, Department Chairs, Division Directors and others who sign off on the "Blue Sheet" for grant submissions
6. MUSC Departmental Research Compliance Officers and Liaisons, VA Research Compliance Officers
7. MUSC Central Administrators who oversee research
8. Office staff of the VA R&D office, VA R&D, Biosafety and IACUC Committee members

1. Part-time research nurses
2. Individuals who directly collect or provide human tissues or fluids or medical/personal data for explicit use in a research Tissue Bank or for human subjects research, but whose participation is less substantial than those described above
3. Technicians who handle human tissues or fluids for human subject research, but whose participation is less substantial than those described above
4. Managers of human subjects research data bases whose participation is less substantial than those described above

1. Study coordinators
2. Research nurses
3. Other individuals that function in such capacities regardless of job title
4. Investigators may choose to take the Research Coordinator Development Program or may be required to attend as part of a corrective action plan as determined by the Board. 

Assessment of the risk/benefit ratio and the importance of the knowledge that may reasonably be expected to result,

Risks to subjects are minimized,

Equitable selection of subjects,

Informed consent is sought from each prospective subject or the subject's legally authorized representative,

Consent will be appropriately documented,

Appropriate collection of safety data,

Issues of privacy and confidentiality and

Attention to special populations. 

Checklist for Expedited Continuing Reviews

Expedited Review Form

IRB Reviewer Checklist (Full Board Review)

Special Subject Populations

Informed Consent Document
HIPAA Authorizations/Waiver of Authorizations
Research Involving Prisoners

Full Board Amendment

Foreign Language Review Form

Initial Review - Exempt - Primary Reviewer only

Exempt form

Human Research Review Application - all reviewers

Request for Expedited Review if applicable - primary

Human Subjects document - all reviewers

Advertisements if applicable - all reviewers

Informed Consent(s) or Waiver of Consent or Waiver of Written Consent forms - all reviewers

Conflict of Interest form if applicable - primary

Off Campus Study Site form if applicable - primary

VA Supplement if applicable - primary

Protocol - primary

Complete Grant Application if applicable - primary

Internally Sponsored or Unsponsored Research form if applicable - primary

Non-Sponsored Budget Form if applicable - primary

Investigational New Drug Information Sheet A if applicable - all reviewers

Marketed Drug Information Sheet B if applicable - all reviewers

Oncology Group/NCI Drug Sheet C if applicable - all reviewers

Medical Device Information Sheet D if applicable - all reviewers

Investigator Drug Brochure if applicable - primary
HIPAA Authorization/Waiver of Authorization - primary

Continuing Review form - all reviewers

Current IRB approved Informed Consents - all reviewers

IRB file that includes the initial application, all amendments, internal and external adverse events, investigator drug brochures if applicable, informed consents, protocol deviation reports and all other applicable forms that pertain to the study - primary

Request for Amendment form - all reviewers

Revised documents (informed consents, protocol, advertisements) - all reviewers

IRB file that includes initial application, all amendments, internal and external adverse events, investigator drug brochures if applicable, informed consents, protocol deviation reports, HIPAA forms and all other applicable forms that pertain to the study - primary
Request for HIPAA Amendment - primary

Compliance audit report - all reviewers

Principal Investigator response to audit report - all reviewers

Correspondence  - all reviewers

1. Upon receipt of an application, the paper copy is checked for appropriate signatures. 
2. Study personnel listed on the application are checked against the Compliance Office database to ensure the required Institutional Training has been completed.  If not all personnel have completed the training, a letter is sent to the Principal Investigator informing him/her that IRB approval of the study will not be released until the certification has been submitted to the IRB office.
3. If the study coordinator has not completed the RCDP, a letter is sent to the Principal Investigator informing him/her that successful completion of the program must occur by the conclusion of the next scheduled course offering, or enrollment into the study will be suspended until the requirement is completed.
4. If educational requirements and signatures are complete, then a HR# is assigned to the study.
5. The study is given to the Chair or his/her designee for review.
6. If the Chair has questions or concerns, the Principal Investigator is notified via email by the IRB staff.  Principal Investigator responses are given to the Chair for review.
7. If responses are satisfactory and if the research fits the Exempt criteria, then the Chair will approve the application; the IRB staff will enter the approval information in the database and release the hard copy to the Principal Investigator.
8. If the Chair makes the decision that the research does not fit the Exempt criteria, then the IRB staff will send a cover letter and a copy of the Exempt form to the Principal Investigator informing them of the Chair's decision.  The Principal Investigator also has access to the status of the study via the electronic database.

(1) Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (a) research on regular and special educational strategies, or (b) 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 observations of public behavior, unless: (a) information is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects and (b) 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 public behavior that is not exempt under paragraph 2(b) of this section, if (a) the human subjects are elected or appointed public officials or candidates for public office; or (b) federal statue(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.  *Existing means already collected and on the shelf; not collected for purposes of the research.

(5) Research and demonstration projects which are conducted by or subject to the approval of department or agency head and which are designed to study, evaluate, or otherwise examine: (a) public benefit or service programs; (b) procedures for obtaining benefits or services under those programs; (c) possible changes in or alternatives to those programs or procedures; or (d) 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,  (a) if wholesome foods without additives are consumed or (b) if a food is consumed that contains a food ingredient at or below the level found to be safe, or agricultural, chemical 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.

1. Investigators submit protocols to the IRB using an IRB application packet that includes:
2. Answers to the Use of Human Subjects Section
3. Plans for recruitment and enrollment procedures
4. Equitable selection of subjects
5. Provisions to protect privacy of subjects and confidentiality of data
6. Additional safeguards to protect rights and welfare of subjects who might be vulnerable
7. Payment to subjects
8. Informed consent document(s)
9. Research protocol
10. Complete HHS grant application (if applicable)
11. Applicable data sheets on status of drugs and devices:
12. Form 1571, and 1572 (if applicable)
13. Principal Investigator C.V. (if applicable)
14. Investigator's drug brochure (if applicable)
15. Information on conflict of interest
16. The VA may require additional forms

1. 46.103(b)(5) - Reporting any unanticipated problems involving risks to subjects or others upon discovery to the IRB staff in writing. 
2. 46.115(b) - Maintaining records relating to the research for at least three years after the conclusion of the study.
3. 46.115(a)(7) - Maintaining records of notification to subjects when there were
4. significant new findings that may have effected the subjects' willingness to continue participation.
5.  Complying with all requirements for informed consent including seeking consent only under conditions that allow the subject or the subject's legally authorized representative sufficient opportunity to consider whether or not to participate and that minimize the opportunity for coercion or undue influence.
6.  Maintaining copies of all pertinent information related to the research activities in this project including copies of informed consent agreements obtained from participants.
7.  Submitting proposed changes in research for IRB approval, and receiving IRB approval before implementing the changes.
8.  Submitting timely continuing review reports to the IRB on progress of the project as required by the IRB.
9.  Notifying the IRB immediately upon termination of a project and/or the departure of the principal investigator from this Institution and the project.
10.  Maintaining data and other research products produced under this research in a central location in a manner that will allow other qualified scientists to verify the accuracy and integrity of reported results of the research.
11. Individuals supported in whole or in part by the research and who are in a training status will be given explicit training in the responsible conduct of research.
12. Any individual who has a substantive scientific role in the proposed research has been provided a copy of the application and has had an opportunity to comment on it.
13. Criteria for authorship of publications resulting from the proposed research have been discussed and agreed to by the professional staff of the laboratory.
14. Scientists who have a substantive scientific role in the proposed research do not have any financial interests that could affect the objectivity of the research.
15. Any material in the grant application/protocol that is a verbatim reproduction of other persons' writings has been identified by quotation marks and properly attributed.
16. If the PI is unable to direct this research personally, as when on sabbatical leave or vacation, they will arrange for a co-investigator to assume direct responsibility in their absence.
17. Study personnel will have completed the mandatory educational compliance training on human research.

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Expedited

An investigator may request expedited review by completing the Human Research Review Application and all applicable attachments and checking the appropriate categories for expedited review.  Research may not be disapproved by this mechanism; it can only be referred to the Full Board for review.  All studies involving FDA regulated products will be reviewed and approved under FDA regulations. 

1.  Upon receipt of an application, the application is stamped with the date of receipt.  The application is checked for appropriate signatures. 
2. Study personnel listed on the application are checked against the Compliance Office database to ensure the required institutional training has been completed.  If not all personnel have completed training, a letter is sent to the PI informing him/her that IRB approval of the study will not be released until certification has been submitted to the IRB office.
3. If the study coordinator has not completed the RCDP, a letter is sent to the Principal Investigator informing him/her that successful completion of the program must occur by the conclusion of the next scheduled course offering, or enrollment into the study will be suspended until the requirement is completed. 
4. If educational requirements and signatures are complete, then a HR# is assigned to the study and the study is assigned to the appropriate IRB as determined by the funding source and specialty content.  IRB I and IRB II are divided by departments.  IRB III reviews all industry-sponsored protocols from all departments.
5. The IRB Administrator reviews the application for regulatory compliance and adherence to established IRB guidelines. 
6. The IRB Chair, Vice-Chair or the Chair's designee then reviews the application.
7. Questions or comments by reviewers will be emailed or faxed to the Principal Investigator and study coordinator by the Administrator.
8. The Administrator and Chair will check the investigator's responses.
9. If responses are satisfactory and the study constitutes minimal risk to subjects, then the Chair will approve the study under the Expedited criteria. 
10. The Administrator will enter approval information into the database; IRB staff will release the approval to the Principal Investigator.
11. Approval of the application is reported to the full Board at a convened meeting.
12. If the application does not fulfill the criteria for expedited review, then the study will be processed for full Board review.

1. All information required per procedures has been included in the submission,
2. Risks to subjects have been minimized by using sound research design, or, whenever appropriate, using procedures already being performed on the subject for diagnostic or treatment purposes,
3. Risks, including physical psychological, social and economical, are reasonable relative to anticipated benefits,
4. Selection of subjects is equitable,
5. When required, documented informed consent must be obtained in compliance with MUSC policies and federal regulations,
6. Provisions are adequate to protect the privacy of subjects and maintain confidentiality of the data,
7. If the research subjects include a vulnerable group, additional safeguards have been included to protect the rights and welfare of these subjects and all special requirements for the populations have been adequately addressed,
8. Determine the frequency of continuing review.

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Applicability:

1. Research activities that (1) present no more than minimal risk to human subjects, and (2) involve only procedures listed in one or more of the following categories, may be reviewed by the IRB through the expedited review procedure authorized by 45 CFR 46.110 and 21 CFR 56.110.  The activities listed 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 the specific circumstances of the proposed research involve no more than minimal risk to human subjects.  Minimal risks means that the probability and magnitude of harm or discomfort anticipated are not greater in and of themselves than ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
2. The categories in this list apply regardless of the age of subjects, except as noted.
3. The expedited review procedure may not be used where identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects= financial standing, employability, insurability, reputation, or be stigmatizing, unless reasonable and appropriate protections will be implemented so that risks related to invasion of privacy and breach of confidentiality are no greater than minimal.

1. (1) Clinical studies of drugs and medical devices only when condition (a) or (b) is met.
   1. Research on drugs for which an investigational new drug 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.)
   2. Research on medical devices for which (i) an investigational device exemption 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:

   1. from healthy, nonpregnant adults who weigh at least 110 pounds.  For these subjects, 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
   2. from other adults and children, considering the age, weight, and health of the subjects, the collection procedure, the amount of blood to be collected, and the frequency with which it will be collected.  For these subjects, 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 by noninvasive means.  Examples: (a) Hair and nail clippings in a nondisfiguring 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)= (e) uncannulated saliva collected either in an unstimulated fashion or (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 subgingival dental plaque and calculus, provided the collection procedure is no 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.  (Studies intended to evaluate the safety and effectiveness of the medical device are not generally eligible for expedited review, including studies of cleared medical devices for new indications.)  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, eletroretinography, 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 nonresearch 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 subjects; (ii) all subjects have completed all research?related interventions; and (iii) the research remains active only for long?term follow?up of subjects; or

   (b) where no subjects 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.
   
   

   1 An expedited review procedure consists of a review of research involving human subjects by the IRB chair 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).

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Full Board Review
All other research involving human subjects must be reviewed and approved by the Full Board at a convened meeting.   All full Board applications are placed on the agenda at a convened meeting where appropriate discussion and voting for approval, modification, or disapproval take place.  The Chair or a reviewer may request that an investigator attend the meeting.  All studies involving FDA regulated products will be reviewed and approved under FDA regulations.  The prisoner representative must be present as a voting member at a convened meeting for all studies that include prisoners (including initial review, continuing review, amendments and review of unanticipated problems involving risks to subjects or others).

1. Upon receipt of an application, the application is stamped with the date of receipt.  The application is checked for appropriate signatures. 
2.  Study personnel listed on the application are checked against the Compliance Office database to ensure required Institutional Training has been completed.  If not all personnel have completed training, a letter is sent to the PI informing them that IRB approval of the study will not be released until certification has been submitted to the IRB office.
3.  If the study coordinator has not completed the RCDP, a letter is sent to the PI informing them that successful completion of the program must occur by conclusion of the next scheduled course offering, or enrollment into the study will be suspended until the requirement is completed. 
4. If educational requirements and signatures are complete, then a HR# is assigned to the study. 
5.  The application is assigned to the appropriate IRB and is given to the IRB Administrator who administratively reviews for regulatory compliance and adherence to established guidelines.
6. The application is sent to the Primary Review Group between two and three weeks prior to the convened meeting.  Each Primary Review Group includes at least one scientific member and one non-scientific member as well as other reviewers.  No reviewer will review a study if he/she has a conflict of interest.  The Administrator will assign studies to Primary Review Groups relative to expertise of the members.   As determined by the IRB Administrator, appropriate parts of the OHRP and FDA regulations are referenced or attached to the application package for use by the reviewers.  The remaining reviewers are sent the Review Application, Human Subject document, and Informed Consent document(s) and any advertisements.  The Administrator will request Reviewer critiques by a deadline.
7. The Administrator will enter reviewer comments into the database.  A cover letter that gives the Principal Investigator a deadline in which to respond to the Board's concerns and the reviewer comments will be sent to the Principal Investigator and study coordinator by email or fax.
8. The Administrator will review the Principal Investigator response and prepare it for the Board's review.
9. The Administrator will prepare the agenda that is delivered to the reviewing Board members on the Friday before the Tuesday convened meeting.
10. Late or additional Principal Investigator responses that come in after the agenda has been sent out will be presented to the Board at the meeting.
11. During the meeting, each study is presented, discussed and voted on individually. 
12. The Board can approve, require further modifications, table, or disapprove a study.  If minor changes are required, they may be reviewed and approved by the Chair or the Chair's designee.  Changes that are substantive in nature must be brought back to the full Board at a convened meeting.
13. If the study is approved without further changes, the Administrator will prepare the approval for release. 
14. If the study requires further modifications that are minor in nature, the Administrator will notify the Principal Investigator and study coordinator by email or fax.  When revisions are received in the IRB office, the Administrator and the Chair will review them; if acceptable, the Chair will sign the approval and the Administrator will prepare the study for release by the IRB staff.
15. If modifications are substantive in nature or if the Board tables or disapproves the study, the Chair will notify the Principal Investigator in writing.
16. Principal Investigator responses to substantive modifications or rewrites due to disapproval are presented to the Full Board for review, discussion and vote at a convened meeting.  If approved, then the Administrator will prepare the study for release by the IRB staff.
17. If a Principal Investigator has appealed the Board's decision in writing to the Chair, the Administrator will place the item on the next available agenda for full Board discussion and vote and will notify the Principal Investigator of the date, time and place of the meeting.
18. The Administrator prepares Minutes of the convened meeting, which are approved by the Chair and the Board.  Minutes show attendance at meetings and actions taken by the Board including the level of risk and frequency of continuing review.  Minutes document the vote on all IRB actions including the number voting for, against, and those abstaining. 

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The Board is divided into comparable groups of three to five members each. Each Primary Review Group includes at least one scientific member and one non-scientific member as well as other reviewers.  These members act as primary reviewers for a portion of the protocols submitted for the review period (i.e. 30 protocols, each group would review ten.)  If a reviewer is unable to attend a meeting, the reviewer is responsible for selecting an appropriate alternate.  The reviewers should return their Reviewer Checklist and Comment Sheets by the deadline assigned by the Administrator.

Primary reviewers check each submission for the following and must record their comments on the Reviewer Checklist.

1. All information required per procedures has been included in the submission,
2. Risks to subjects have been minimized by using sound research design, or, whenever appropriate, using procedures already being performed on the subject for diagnostic or treatment purposes,
3. Risks, physical, psychological, social and economic, are reasonable relative to anticipated benefits,
4. Selection of subjects is equitable,
5. Informed consent document and process when required, must be obtained in compliance with MUSC policies and federal regulations,
6. Provisions are adequate to protect the privacy of subjects and maintain confidentiality of the data,
7. If the research subjects include a vulnerable group, additional safeguards have been included to protect the rights and welfare of these subjects and that all special requirements for the populations have been adequately addressed,
8. Determine the frequency of continuing review.

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Continuing review of on-going research is just as important if not more important than the initial review.  It is only after subjects have been enrolled that both the PI and the IRB can make an evidence-based risk/benefit assessment.  Federal regulations found at 45 CFR 46.109(e) require the IRB to conduct continuing review of research at intervals appropriate to the degree of risk, but not less than once annually.  The regulations also give the IRB the authority to have a third party observe the consent process and the process of research. 

IRB Office Procedures Relative to Continuing Review:

Approximately two months prior to the expiration date, the IRB Coordinator will send the Principal Investigator an IRB Reminder of Approval Expiration.  If continuing reviews are not submitted to the IRB by the deadline, the IRB Coordinator will send a final notice to the Principal Investigator.  This notice is copied to the Principal Investigator's Department Chair and the Provost.

Upon receipt of an application, the hard copy is checked for appropriate signatures. 

Study personnel listed on the application are checked against the Compliance Office database to ensure the required institutional training has been completed.  If not all personnel have completed the training, a letter is sent to the Principal Investigator informing him/her that IRB approval of the study will not be released until the certification has been submitted to the IRB office.

If the study coordinator has not completed the RCDP, a letter is sent to the Principal Investigator informing them that successful completion of the program must occur by the conclusion of the next scheduled course offering, or enrollment into the study will be suspended until the requirement is completed. 

The application is assigned to the appropriate IRB and is given to the IRB Coordinator.  The Coordinator maintains a continuing review logbook then administratively reviews for regulatory compliance and adherence to established guidelines.  This includes administrative review of the application for completeness and accuracy of demographic data reported as well as administrative review of the informed consent.  If the application is incomplete, the IRB Coordinator will contact the Principal Investigator and study coordinator via email or fax prior to the IRB meeting.  The IRB Coordinator will check the Principal Investigator responses for completeness. If the application is complete, the study is given to the Primary Reviewer. 

The IRB Coordinator will prepare continuing review approval forms for the signature of the Primary Reviewer and will enter approval information in the database; IRB staff will release approvals.

If the Principal Investigator does not submit a continuing review form or does not address the IRB's concerns and the IRB approval expires, then the IRB Coordinator sends the Principal Investigator a Letter of Expiration that informs the Principal Investigator to stop enrollment.

The Primary Reviewer reviews the entire IRB folder that includes the initial application, all amendments, all adverse event reports, data safety monitoring reports, investigator drug brochures, informed consents and all previous continuing review applications.

If the Primary Reviewer has questions or concerns, he/she may contact the Principal Investigator or ask the IRB Coordinator to contact the Principal Investigator .  The Primary Reviewer will check the Principal Investigator responses.   If responses are satisfactory, then the Primary Reviewer will sign the Continuing Review form. 

If the review fits the Expedited Categories under 45 CFR 46.110 for continuing review, the IRB Coordinator will enter the approval information into the database and prepare the approval. The Primary Reviewer will determine the appropriate frequency of continuing review and sign the approval form.  The IRB staff will release the approval.  

 If the study requires Full Board review, the IRB Coordinator will place the continuing review on the agenda for the appropriate convened meeting.  Each reviewing IRB member will receive a copy of the Continuing Review Form and the informed consent(s) in the agenda packet that is sent out Friday before the Tuesday meeting.  Late applications will be presented to the Board at the convened meeting.

The IRB must determine which projects need verification from sources other than the investigators that no material changes have occurred since previous IRB review such as:  randomly selected projects; complex projects involving unusual levels or types of risk to subjects; projects conducted by investigators who previously have failed to comply with regulatory requirements; and projects where concern about possible material changes occurring without IRB approval have been raised based upon information provided in continuing review reports or Compliance Audits.

During the convened meeting, each continuing review is presented to the Board by the Primary Reviewer.  The Primary Reviewer makes a recommendation to the Board relative to re-approval of the study.  The Board will consider the following:  no changes, changes due to adverse events, amendments and change due to risk / benefit ratio.  Each continuing review is discussed and a determination is made regarding the time frame of re-review for the upcoming year.  Examples of studies requiring re-review more frequently than once a year are those with greater risks to subject as evidenced by large numbers of unexpected serious adverse events, or those protocols that are of high risk to subjects.  

Expedited Review Category (8): An expedited review procedure may be used for the continuing review of research previously approved by the convened IRB as follows:

1. Where:
   the research is permanently closed to the enrollment of new
   subjects;
   all subjects have completed all research-related interventions;
   and the research remains active only for long-term follow-up of
   subjects; or
2. Where no subjects have been enrolled and no additional risks have been identified; or
3. Where the remaining research activities are limited to data analysis.
   

Of note, category (8) identifies three situations in which research that is greater than minimal risk and has been initially reviewed by a convened IRB may undergo subsequent continuing review by the expedited review procedure.

Expedited Review Category (9):
Under Category (9), an expedited review procedure may be used for continuing review of research not conducted under an investigational new drug application or investigational device exemption where categories (2) through (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.

The Chair will notify appropriate agencies, departments and administration officials of non-compliance with annual review resulting in IRB suspension of approval.

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The Principal Investigator is responsible for developing and maintaining a system for expiration dates of protocols and should not rely on the IRB for reminders of expiration.

The Principal Investigator will submit continuing reviews in a timely manner as requested by the IRB.

The Principal Investigator is responsible for submitting a complete and accurate continuing review report with appropriate informed consent(s) attached.

The Principal Investigator will not enroll subjects if IRB approval expires.

Adverse Events (revised 12/15/05):

Reportable Adverse Events and Unanticipated Problems

Internal Adverse Events

Internal events include Drugs, Biologics, Devices, Loss of Confidentiality, Privacy Issues or Harm to Others: An unanticipated and related or possibly related, serious or more prevalent event occurring during a research study. Report on-line as soon as possible but no later than 10 working days after the investigator first learns of the event.

Fatal - Internal: Report all that occur during the study or 30 days post termination from protocol. Report whether expected or unexpected, related, possibly related or unrelated. Reports must be submitted on-line as soon as possible, but no later than 10 working days after PI learns of the event.

External Adverse Events

External events include Drugs, Biologics, Devices, Loss of Confidentiality, Privacy Issues or Harm to Others: Report on-line as soon as possible but no later than 10 working days after the investigator first learns of the event.

The following conditions must be met for an external adverse event to be reportable to the IRB. 

1. The event has been reviewed by the Central Monitoring Entity (CME) for the study (e.g., a Data Safety Monitoring Board (DSMB) or a Data Monitoring Committee (DMC), a coordinating or statistical center, or other sponsor monitoring entity – see definition below). 
2. The central monitoring entity has determined that the particular adverse event or series of adverse events represent(s) an unanticipated problem which involves risks to subjects or changes the risk/benefit ratio for the study.
3. The external AE report includes the decision of the central monitoring entity regarding recommendations for action.  Examples of such recommendations might include modification of inclusion or exclusion criteria to mitigate the newly identified risks; implementation of additional monitoring procedures of subjects; termination of enrollment of new subjects; modification of informed consent documents to include a description of newly recognized risks; and provision of additional information about newly recognized risks to previously enrolled subjects. 

For any report of an external adverse event determined not to be an unanticipated problem, the local investigator maintains a copy of the external adverse event report and documentation of the basis for this determination.  Local investigators should document their analysis of all external AEs, and this documentation is subject to review or audit by the IRB or designated compliance arm.

See the following site for:

1.  Examples of Adverse Events that Do Not Represent Unanticipated Problems and Do Not Need to be Reported (Appendix B), and

2.  Examples of Adverse Events that Represent Unanticipated Problems and Need to be Reported (Appendix C). http://www.hhs.gov/ohrp/policy/AdvEvntGuid.htm

Fatal - External: Report all that occur during the study or 30 days post termination from protocol only if they meet reportable criteria above. 

Definitions:

Central Monitoring Entity (CME):  The group charged with reviewing the accumulated data to monitor safety, effectiveness, and trial conduct issues as the trial progresses.  This group receives and analyzes all adverse events and other reports for the purpose of identifying and communicating important new safety information. 

Clinical trials may identify a Data Safety Monitoring Board (DSMB) or Data Monitoring Committee (DMC) as the central monitoring entity. 

MedWatch, the FDA Safety Information and Adverse Event Reporting Program, is not a central monitoring entity. 

Unanticipated Problem:  An unanticipated problem may be identified in various ways, one of which is an adverse event.  "Unanticipated problems involving risks to human subjects or others" include those events that (1) are not expected given the nature of the research procedures and the subject population being studied; and (2) suggest that the research places subjects or others at greater risk of harm or discomfort related to the research than was previous known or recognized. 

Unexpected / Unanticipated (adverse event): Not identified in nature, severity or frequency in the current protocol, informed consent, investigator brochure or with other current risk information.

Serious: Results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, cancer, overdose or causes a congenital anomaly/birth defect.

More Prevalent: Adverse events that occur more frequently than anticipated or are more prevalent than expected. Example: nausea noted in consent as occurring in 10% of subjects - if 35% of subjects experience nausea, then report as an adverse event.

All other (expected adverse events): Report as aggregate data at time of continuing review.

Related:There is a reasonable possibility that the adverse event may have been caused by the drug, device or intervention.

Possibly Related: The adverse event may have been caused by the drug, device or intervention, however there is insufficient information to determine the likelihood of this possibility.

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IRB Office Procedures Relative to Adverse Events

Adverse event reports are reviewed in the database by the Primary Reviewer.

The informed consent is reviewed relative to the internal or external adverse event.

The IRB Chair or Vice-Chair is notified of situations needing immediate action.

IRB staff will contact the Principal Investigator via email or fax if the Primary Reviewer has questions.

A Primary Reviewer is the Chair, Vice-Chair or the Chair's designee.
The Primary Reviewer will:

1. Review the adverse events, protocol, previous adverse events, investigator drug brochure if applicable and informed consent document.
2. May contact the Principal Investigator regarding the adverse event.
3. Determine if there is increased risk changing the benefit /risk ratio of participation and/or not described in the consent.
4. Report the event and make recommendations to the Full Board for action as needed.  This action can include:

   No action needed
   Revision of informed consent
   Inform currently enrolled subjects of changes
   Stop protocol until more information is available

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Changes made to the informed consent, protocol, or authorization must be submitted for prospective IRB review and approval except where necessary to eliminate apparent immediate hazards to subjects.  This is addressed in training programs and educational sessions.

The PI will not implement changes until prospective IRB review and approval has occurred.
Investigators submit requests for change on the Request for Amendment form. 
The PI indicates whether the change is minimal risk or greater than minimal risk.
The PI must clearly mark changes in the documents revised by the amendment and submit an unmarked revised version of the informed consent/authorization if applicable.  A master copy of the amended informed consent/authorization document, with an original IRB approval stamp,is sent to the Principal Investigator.  If the amended informed consent/authorization document replaces an existing informed consent/authorization document, the existing informed consent/authorization document should be clearly marked "OBSOLETE". The Principal Investigator is also responsible for ensuring any unused copies of the obsolete informed consent/authorization document are discarded. 

Primary Reviewer Responsibilities Relative to Amendments:
Review the amendment with the informed consent/authorization and protocol.  Determine whetherthe risk is minimal (no increase in risk/benefit ratio); refer to the Full Board if greater than minimal risk.  Contact investigator if necessary. Make recommendation of approval, additional changes or disapproval to the full Board.

IRB Office Procedures Relative to Amendments:
The Amendment is entered into the database and assigned to the appropriate IRB. 
The IRB Coordinator administratively reviews the amendment for completeness and accuracy according to federal regulations and notifies the PI via email or fax if there are questions.

Notify Chair if request is urgent or an emergency.  When the amendment is complete, it is given to the Primary Reviewer.  If the IRB Coordinator questions the level of review that is requested, this is brought to the Primary Reviewer's attention.  If the Primary Reviewer approves the amendment by expedited review, then the IRB Coordinator enters the approval information into the database and releases the approval to the PI.

If the amendment requires Full Board review, the IRB Coordinator sends the amendment request with the Primary Reviewers recommendations to the reviewing members with the Agenda on the Friday prior to the convened meeting.

If the amendment is approved at the meeting, the IRB Coordinator enters the approval into the database, prints the approval for the Chair's signature and releases the approval to the PI.

The new version of the informed consent/authorization is date stamped with the amendment approval date.  The original informed consent/authorization document is retained for IRB records.  A master copy of the amended informed consent/authorization document, with an original IRB approval stamp, is sent to the Principal Investigator. 

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A protocol deviation is a deviation committed by the research team that involved the inclusion/exclusion criteria; dose, dosage schedule, or use of device; use of medications not allowed by the protocol; other.

PI Responsibilities Relative to Protocol Deviations:
The PI should report protocol deviations committed by the research team to the IRB on the Protocol deviation report form.

IRB Office Procedures Relative to Protocol Deviations:
The protocol deviation is given to the appropriate IRB Administrator.  The file is pulled and given to the Primary Reviewer with the form.  Protocol deviations are reported to the Full Board at a convened meeting.

Primary Reviewer Responsibilities Relative to Protocol Deviations:
A Primary Reviewer can be the Chair, Vice-Chair or the Chair's designee.  The Primary Reviewer reviews the Protocol Deviation with the protocol; presents the deviation to the Full Board for further recommendation. 

Protocol Violations:
Protocol violations constitute research not conducted in accordance with IRB requirements.

If a protocol violation occurs or is suspected, the IRB Chair or Vice-Chair will notify the investigator in writing.  The investigator will respond within five working days.
Upon receipt of the response, the full Board will decide on further action.  If no response is received, the IRB will request further action from the Provost and University Officials.

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The Principal Investigator submits informed consent documents to the IRB for review and approval.  Once the informed consent document has been approved, the original copy is stamped with the IRB approval date by the IRB Staff, and retained in IRB records.  A Master Copy with an original IRB approval stamp is sent to the Principal Investigator.  Copies are to be made only from the Master Copy, which is identified by the original IRB date stamp.  No copies are to be made from word processing files or from any other copy without the original stamp.No informed consent, whether written or oral, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights, or release or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.  45 CFR 46.116

Investigators follow the MUSC Informed Consent Guide when writing informed consents.  The guide includes the following required elements of informed consent 45 CFR 46.116(a)(1) and must be written in lay language:

1. A statement that the study involves research;
2. An explanation of the purpose of the study; 
3. A description of the procedures to be followed; 
4. Identification of any procedures that are experimental;
5. The expected duration of the subject's participation;
6. A description of nay reasonably foreseeable risks or discomforts to the subject;
7. A description of any benefits to the subject or to others which may reasonably be expected from the research;
8. A disclosure of alternative procedures or courses of treatment, if any, that might be advantageous to the subject;
9. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
10. For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments areavailable if injury occurs and, if so, what they consist of, or where further information may be obtained;
11. An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject; and
12. A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and thesubject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.

Additional elements of informed consent may be provided when appropriate under 45 CFR 46 116(1):

Informed consent must be obtained from the subject, spouse, court-appointed legal guardian, or from the parent of a minor less than 18 years of age by the person(s) approved by the IRB to obtain consent.  Children ages 12-17 must give their assent for participation.  One witness to the subject's signature is required.  Signatures must be dated.  Deviation from this standard must be reviewed and approved by the full IRB at a convened meeting on a case-by-case basis.  Next-of-kin may not give consent unless specifically approved by the IRB.

An investigator may request a waiver of consent, an alteration of consent elements under 45 CFR 46.116(d) or a waiver of written informed consent under 45 CFR 46.117© by filling out the appropriate Request for Waiver form. 

Informed consents must be written in a language understandable to subjects.  Consents in a foreign language must be submitted to the IRB.  The IRB will obtain an interpreter to confirm that the consent written in the foreign language is identical to the English version.  The interpreter will sign a statement of confidentiality.   If the IRB approves an oral presentation of the informed consent for non-English speaking subjects, both the oral presentation and the short form document should be in a language understandable to the subject; the IRB-approved English language consent document may serve as the summary and the witness should be fluent in both English and the language of the subject.

NIH-Supported Clinical Trials - IRB Review of NIH-Approved Informed Consent Documents:
The IRB must review and approve the NIH-approved sample informed consent document in junction with the NIH-approved protocol.  Any deletion or substantive modification information concerning risks or alternative procedures contained in the sample consent must be justified in writing by the investigator, approved the IRB and reflected in the IRB minutes.

Description of Notification of HIV Testing Results:
PHS policy (applicable to all PHS-supported intramural and extramural, foreign and domestic research and health activities) requires that where HIV testing is conducted or supported by PHS, individuals whose test results are associated with personal identifiers must be informed of their own test results and provided the opportunity to receive appropriate counseling unless the situation calls for an exception under the special circumstances set forth in the Policy.  This procedure should be described in the informed consent document.

IRB Review in Emergency Situations: 45 CFR 46.103(b) and 46.116(f)
HHS regulations do not permit human subject research activities to be started, even in an emergency, without prior IRB review and approval.  When emergency medical care is initiated without prior IRB review and approval, the patient may not be considered a research subject under 45 CFR 46.  Such emergency care may not be claimed as research, nor may any data regarding such care be included in any report of a prospectively conceived research activity.  When emergency care involves investigational drugs, devices, or biologics, FDA requirements must be satisfied.

Emergency Use of Investigational Drugs and or Devices: FDA regulations Emergency use is defined as the use of an investigational drug or biological product with 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.   21 CFR 56.102(d) Investigators should contact the IRB for further guidance.

Exception from the Informed Consent Requirement for an emergency use is found at FDA 21 CFR 50.23(a).  Investigators should contact the IRB for further guidance.

1. Issues of noncompliance and unanticipated problems involving risks to human research subjects or others initially will be reviewed by the IRB Program Manager and IRB Chair.
   
2. The IRB Program Manger and the IRB Chair will conduct a preliminary investigation to determine the nature of the noncompliance a