SOP 400 Review of Research (RR)
401 Expedited Review
1. OBJECTIVE
An expedited review procedure consists of a review of research involving human subjects by the Chairperson or by one or more experienced reviewers designated by the Chairperson from among members of the IRB.
Specific Procedures
1.1 Definition of Minimal Risk
Minimal risk is defined as “...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….”
The IRB may use an expedited review procedure to review either or both of the following:
- Some or all of the research which involves only procedures listed in one or more of the categories below and found by the reviewer(s) to involve no more than minimal risk;
- Minor changes in previously-approved research during the IRB approval period;
Expedited research categories
- Category 1: Clinical studies of drugs and medical devices only when either condition below is met:
- Research on drugs for which an investigational new drug application (21 CFR 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;
- Research on medical devices for which (1) an investigational device exemption application (21 CFR 812) is not required; or (2) the medical device is cleared/approved for marketing and the medical device is being used in accordance with its cleared/approved labeling.
- Category 2: Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows:
- From healthy, nonpregnant adults who weigh at least 110 pounds. For these subjects, the amounts drawn may not exceed 550 ml in 44 an 8 week period and collection may not occur more frequently than 2 times per week; or
- 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.
- Category 3: Prospective collection of biological specimens for research purposes by noninvasive means. Examples include:
- Hair and nail clippings in a nondisfiguring manner;
- Deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction;
- Permanent teeth if routine patient care indicates a need for extraction;
- Excreta and external secretions (including sweat);
- 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;
- Placenta removed at delivery;
- Amniotic fluid obtained at the time of rupture of the membrane prior to or during labor;
- Supra- and subgingival 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;
- Mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; or
- Sputum collected after saline mist nebulization.
- Category 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:
- 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;
- Weighing or testing sensory acuity;
- Magnetic resonance imaging;
- Electrocardiography; electroencephalography, thermography detection of naturally occurring radioactivity, electroretinography, ultrasound, diagnostic infrared imaging, Doppler blood flow, and echocardiography;
- Moderate exercise, muscular strength testing, body composition assessment and flexibility testing where appropriate given the age, weight and health of the individual.
- Category 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.
- Category 6: Collection of data from voice, video, digital, or image recordings made for research purposes. If the data collected is considered individually identifiable health information, the data must be protected from inappropriate use and disclosure.
- Category 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.
- Category 8: Continuing review (i.e. renewal) of research previously approved by the convened IRB as follows:
- 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 longterm follow-up of subjects; or
- Where no subjects have been enrolled and no additional risks have been identified; or
- Where the remaining research activities are limited to data analysis.
- Category 9: Continuing review (i.e. renewal) 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.
1.2 Cautions
1.2.1 The activities listed should not be deemed to be of minimal risk simply because they are included on the list of eligible research. 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.
1.2.2 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. Furthermore, the expedited review procedure may not be used for classified research involving human subjects.
1.3 Authority of the IRB Chairperson
The IRB Chairperson (or designated reviewer) may exercise all of the authorities of the IRB, except that he/she may not disapprove the research. A research proposal may be disapproved only after review by the full IRB.
1.4 Notification of the IRB
When the expedited review procedure is used, all regular members shall be informed of actions taken by the IRB at the next convened meeting.
1.5 Documentation
If the study qualifies for expedited review, the IRB Chairperson or designee will document his/her determination of risk.
The minutes will include documentation of the studies that were reviewed via expedited review. Records are available for member review to answer any concerns.
1.6 Additional Items That May be Reviewed by the Chairperson or Designee
1.6.1 Conditional approval pending minor revisions: Revisions to consent documents and other documentation submitted as a result of full IRB review and as a condition to final approval may be reviewed by the IRB Chairperson or his/her designee. Final approval will be issued providing the revisions or documentation do not indicate or result in a significant change to the study or change in the risk/benefit ratio.
1.6.1 Other Reviews
- The IRB Chairperson may use the expedited review procedure to review minor changes in previously approved research during the period for which approval is authorized. Any protocol revision that entails more than a minimal risk to the subjects must be reviewed by the full IRB at a convened meeting.
- Revisions to informed consent documents: Minor changes to informed consent documents that do not affect the rights and welfare of study subjects, or do not involve increased risk or significant changes in study procedures may be reviewed and approved by the Chairperson/designee.
- Serious adverse event and safety reports: The Chairperson will review all reports concerning adverse events. If the Chairperson feels that action is needed to protect the safety of research subjects due to the nature or frequency of reported adverse events, he/she may take such action to the full IRB or designated subcommittee, which will review the adverse events and study in question to determine action, if any, by the IRB. The IRB Chairperson acting for the IRB will review summaries of safety reports and serious adverse events as soon as possible.
- Advertisements: The IRB Chairperson, or his/her designee may approve new or revised recruitment advertisements or scripts.
1.6.2 Translations:
- Translations of consent documents will also be submitted for IRB approval and will be reviewed in an expedited manner.
2. SCOPE
These policies and procedures apply to all research submitted to the IRB(s) that qualifies for expedited review.
3. APPLICABLE REGULATIONS AND GUIDELINES
45 CFR 46.102(i), 46.110
21 CFR 56.110
OHRP IRB Guidebook
4. REFERENCES TO OTHER APPLICABLE SOPs
This SOP affects all other SOPs.
402 Initial Review - Criteria for IRB Approval
1. OBJECTIVE
All research proposals that intend to enroll human subjects must meet certain criteria before study related procedures can be initiated. The criteria are based on the principles of justice, beneficence and autonomy as discussed in the Belmont Report and are specified below. In addition, certain other criteria that are unique to BRIGHAM YOUNG UNIVERSITY's system may apply and must be met as well.
Specific Procedures
1.1 Minimal Criteria for Approval of Research
In order for a research project to be approved, the IRB must find that:
A. Risks to subjects are minimized:
- By using procedures that are consistent with sound research design and which do not unnecessarily expose subjects to risk, and
- Whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes.
B. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result.
- In evaluating risks and benefits, the IRB will consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies that subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.
C. Selection of subjects is equitable.
- In making this assessment the IRB should take into account the purposes of the research and the setting in which 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, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons.
D. Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with and to the extent required by appropriate local, state and federal regulations.
E. Informed consent will be appropriately documented as required by local, state and federal regulations.
F. Where appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.
G. Where appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.
H. When some or all of the subjects, such as children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons, are likely to be vulnerable to coercion or undue influence or for subjects found at international sites, additional safeguards have been included in the study and in the IRB review process, to protect the rights and welfare of these subjects.
I. Studies are reviewed at periods appropriate to the degree of risk research subject are exposed to due to their participation in the study, but at least annually.
1.2 Other Criteria
The IRB may require verification of information submitted by an investigator. The need to verify any information will be determined by the IRB at a convened meeting. The purpose of the verification will be to provide necessary protection to subjects when deemed appropriate by the IRB.
The criteria used to determine whether third-party verification is required may include:
- Investigators that conduct studies that involve a potential high risk to subjects,
- Studies that involve vulnerable populations,
- Investigators that conduct studies that involve large numbers of subjects, and
- Investigators selected at the discretion of the IRB.
Projects that need third party verification from sources other than the Investigator that no material changes have occurred since previous IRB review is determined, will have such assessment performed as necessary.
1.3 Reliance on Other IRBs for Review and Approval of Research Conducted at BRIGHAM YOUNG UNIVERSITY.
Under authority granted by the Board of Trustees of Brigham Young University, the AAVP may enter into joint review arrangements, rely upon the review of another qualified IRB, or make similar arrangements for avoiding duplication of effort as allowed and upon modification of the institutional Multiple Project Assurance/Federal-wide Assurance agreements (MPA/FWA).
2. SCOPE
These policies and procedures apply to all IRB staff and members and to research submitted to the IRB.
3. APPLICABLE REGULATIONS AND GUIDELINES
45 CFR 46.111
21 CFR 56.108, 56.111
4. REFERENCES TO OTHER APPLICABLE SOPs
This SOP affects all other SOPs.
403 Events Requiring Investigators to Report to the IRB
1. OBJECTIVE
No Investigator has a right to conduct research within this institution. Rather, it is a privilege granted by society as a whole and the Trustees of BRIGHAM YOUNG UNIVERSITY in particular.
IRB approval may be withdrawn at any time if warranted by the conduct of the research. The regulations authorize the IRB to establish procedures for the concurrent monitoring of research activities involving human subjects. Periodic review of research activities is necessary to determine whether approval should be continued or withdrawn. All research involving human subjects must be reviewed no less than once per year.
IRB approval for the conduct of a study may be withdrawn if the risks to the subjects are determined to be unreasonably high, for example, more than an expected number of adverse events, unexpected serious adverse events; or evidence that the Investigator is not conducting the investigation in compliance with IRB or Institutional guidelines. Such findings may result in more frequent review of the study to determine if approval should be withdrawn or enrollment stopped until corrective measures can be taken or the study terminated. As appropriate, continuing review may include:
- Review of Serious and Unexpected Adverse Events
- Amendments
- Review of Significant New Findings
- Reports from Employees, Staff and Faculty
- Noncompliance
- Site Visits and Third-Party Verification
Specific Procedures
1.1 Serious and Unexpected Adverse Events
Subject safety is of the greatest importance for both the individual subject and the goals of the clinical study. If the event is serious and unexpected, prompt reporting to the Sponsor and to the IRB is mandatory. Reports will be reviewed by the IRB Chairperson or designee. If the Chairperson determines that action may be needed to protect the safety of research subjects due to the nature or frequency of reported adverse events, he/she may take such action and/or the full IRB or designated subcommittee will review the adverse events and study in question to determine action, if any, by the IRB. The IRB, or designated subcommittee will review summaries of all safety reports and serious adverse events as soon as possible at a convened meeting.
1.2 Amendments
Changes in approved research, during the period for which approval has already been given, may not be initiated without prior IRB review (full or expedited review, as appropriate) and approval, except where necessary to eliminate apparent immediate hazards to human subjects.
Investigators or Sponsors must submit requests for changes to the IRB in writing. Upon receipt of the protocol change, the Chairperson or his or her designee, with assistance of the IRB Administrator, will determine if the revision meets the criteria for minimal risk. If the change represents more than a minimal risk to subjects, it must be reviewed and approved by the IRB. Minor changes, involving no more than minimal risk to the subject, will be reviewed by the expedited review procedure (SOP RR 401-Expedited Review).
1.3 Significant New Findings
During the course of a study, the IRB may review reports generated from adverse event reports, current literature, and other sources to ascertain the status of the study and assess whether or not the risk/benefit balance is still acceptable. The IRB will determine whether or not new information needs to be conveyed to subjects, or if a segment of the population may be bearing an undue burden of research risk or being denied access to promising therapy.
1.4 Reports of Concerns
It is the responsibility of the IRB staff and members to act on information or reports received from any source that indicate a study being conducted at any facility under the jurisdiction of the IRB could adversely affect the rights and welfare of research subjects.
1.5 Ensuring Prompt Reporting of Any Serious or Continuing Noncompliance with Applicable Regulations or the Requirements or Determinations of the IRB
All credible reports of inappropriate involvement of human subjects in research must be investigated by the IRB Chairperson/IRB Administrator and referred to the IRB. The results of the investigation will be reported to the appropriate BRIGHAM YOUNG UNIVERSITY official(s). Regulatory authorities or Sponsors may also be notified. Such reports of noncompliance may come from any source including IRB members, Investigators, subjects, institutional personnel, the media, anonymous sources or the public.
The IRB has the authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB policies, is not in compliance with federal regulations, or has been associated with unexpected serious harm to subjects. All such suspension and or terminations will be reported to the OHRP and FDA as appropriate.
2. SCOPE
These policies and procedures apply to all research submitted to the IRB.
3. APPLICABLE REGULATIONS AND GUIDELINES
45 CFR 46.103, 46.109, 46.112, 46.115
21 CFR 812.64
21 CFR 56.108, 56.109, 56.113
4. REFERENCES TO OTHER APPLICABLE SOPs
This SOP affects all other SOPs.
404 Continuing Review - Criteria for Renewal
1. OBJECTIVE
The IRB conducts continuing review of research taking place within its jurisdiction at intervals appropriate to the degree of risk, but not less than once per year.
Specific Procedures
Studies Confirmed as Exempt
- Studies confirmed as meeting the criteria for exemption are not subject to continuing review. BYU, nonetheless, remains responsible for exercising proper oversight for research conducted under its auspices. To exercise this oversight, the IRB office will annually send a notice to all PIs to confirm:
- That the research is on-going. If it is not, the PI will be asked to close out the study
- That the PI is aware of her/his responsibilities under the BYI IRB approval
Studies Approved by Expedited Review or Convened IRB
1.1 Interval for Review for Purposes of Renewal
The IRB must conduct continuing review of protocols for purposes of renewal of the IRB approval period, at intervals appropriate to the degree of risk, which is determined at the initial review, but not less than once per year. “Not less than once per year" means that the research must be reviewed on or before the one-year anniversary of the previous IRB review date, even though the research activity may not have begun until sometime after the IRB gave its approval.
Investigators or qualified designees are required to submit a periodic report prior to the expiration of the study or as specified by the IRB, but at least annually. The report should normally be filed 60 days before the study approval period ends.
1.2 Extensions of Approval Period
There is no grace period extending the conduct of the research beyond the expiration date of IRB approval. Extensions beyond the expiration date will not be granted. If Continuing Review Report forms and other requested progress reports are not received as scheduled, the Investigator must suspend the study and study enrollment.
However, if the Investigator is in communication with the IRB, the Continuing Review Report or other report is forthcoming, and in the opinion of the IRB, subjects participating is such a study would suffer a hardship if medical care were discontinued, appropriate medical care may continue beyond the expiration date for a reasonable amount of time. However, new subjects cannot be enrolled. The IRB will address on a case-by-case basis those rare instances where failure to enroll new subjects would seriously jeopardize the safety or well-being of an individual.
1.3 Criteria for Renewal
Continuing review must be substantive and meaningful. When considering whether or not to renew a study, the IRB revisits the same criteria used to grant initial approval. Therefore, the IRB (or the reviewers for protocols reviewed under an expedited procedure) must determine that:
- The risks to subjects continue to be minimized and reasonable in relation to the anticipated benefits;
- The selection of subjects continues to be reasonable in relation to anticipated benefits;
- Informed consent continues to be appropriately documented;
- Additionally, there are:
- Provisions for safety monitoring of the data,
- Protections to ensure the privacy of subjects and confidentiality of data, and
- Appropriate safeguards for vulnerable populations.
Because it may be only after research has begun that the real risks can be evaluated and the preliminary results used to compute the actual risk/benefit ratio, the IRB can then determine whether or not the study can be renewed at the same risk/benefit ratio, or if new information has changed that determination.
In order to determine the status of the study, the following will be revisited:
1.3.1 Consent document: Each member of the IRB shall review the currently approved consent document and ensure that the information is still accurate and complete. Any significant new findings that may relate to the subject's willingness to continue participation should be provided to the subject in an updated consent document.
1.3.2 Current approved protocol including any amendments to protocol since initial review: A copy of the protocol will be sent to the reviewer of the continuing review. Amendments to a research protocol should be submitted as generated during the course of the study. They also may be submitted at the time of continuing review. A separate cover letter describing the change and all appropriate documentation (approved consent form) must accompany the continuing review application.
1.3.3 Progress report: All IRB members shall receive a progress report prepared and submitted by the Investigator along with the number of subjects entered to date and since the last review. The progress report shall summarize adverse event experiences, amendments, changes in training of personnel and new COI disclosure as applicable, and provide a reassessment of the risk-to-benefit ratio.
1.4 Possible Outcomes of Continuing Review
As an outcome of continuing review, the IRB may require that the research be modified or halted altogether. The IRB may need to impose special precautions or relax special requirements it had previously imposed on the research protocol.
1.5 Expedited Review for Renewal
A protocol that was originally reviewed using the expedited review procedure may receive its continuing review on an expedited basis. Additionally, a standard-review protocol that meets the continuing review requirements under Expedited Review Category 8 or 9 may undergo expedited review (e.g. no subjects have been enrolled, remaining activities limited to data analysis; see SOP RR 401, Expedited Review for all requirements).
When conducting research under an expedited review procedure, the IRB Chairperson or designated IRB member conducts the review on behalf of the full IRB using the same criteria for renewal as stated in section 1.3 of this Procedure. If the reviewer feels that there has been a change to the risks or benefits, he or she may refer the study to the full IRB for review.
2. SCOPE
These policies and procedures apply to all research submitted to the IRB.
3. APPLICABLE REGULATIONS AND GUIDELINES
45 CFR 46.109, 46.111
21 CFR 56.108,111
4. REFERENCES TO OTHER APPLICABLE SOPs
This SOP affects all other SOPs.
405 Categories of Action
1. OBJECTIVE
As a result of its review, the IRB may decide to approve or disapprove the proposed research activity, or to specify modifications required to secure IRB approval of the research activity. Except when the expedited review procedure is used, these actions will be taken by a vote of a majority of the regular and alternate members present, except for those members present but unable to vote in accordance with the IRB's conflict of interest policies. When reviewed via expedited review, the Chairperson or designee can take any of the following actions except to disapprove a study.
Specific Procedures
1.1 Determinations
The IRB may make one of the following determinations as a result of its review of research submitted for initial review or for continuing review:
A. Approval: The protocol and accompanying documents are approved as submitted. Final approval will commence on the day the study is approved by an action of the convened IRB or Chairperson or designee and, if appropriate, expire within one (1) year of the meeting date, but not later than the day preceding the date of review.
Approvals are always considered conditional. The conditions for continued approval, and the time frame (if any) within which they must be met will be clearly stated in the approval letter. If the conditions of the approval are not met, approval may be withdrawn.
B. Withheld Approval: Minor modification of, or addition to, a protocol or accompanying document(s) is required. Changes will be voted upon during the IRB’s meeting, as well as the terms of approval. The Investigator will be informed in writing of the required changes and requested information and must provide the IRB with the changes or information.
The IRB Chairperson or his/her designee has the authority to review the information via expedited review unless the IRB requires that the material or information be reviewed by the full IRB, the reviewer or another individual delegated by the IRB to review the response. Upon satisfactory review, approval will be issued as of the date that the requested information or materials are approved. However, the expiration date of IRB approval will be based on the anniversary date of the initial IRB review. Subjects must not be recruited into the study until final approval has been issued.
C. Tabled: Significant questions are raised by the proposal requiring its reconsideration after additional information is received from the Sponsor and/or Investigator.
D. Disapproval: The proposal fails to meet one or more criteria used by the IRB for approval of research. Disapproval cannot be given through the expedited review mechanism and may only be given by majority vote at a convened meeting of the IRB.
2. SCOPE
These policies and procedures apply to all research submitted to the IRB.
3. APPLICABLE REGULATIONS AND GUIDELINES
45 CFR 46.108, 46.109
21 CFR 56.109, 56.111, 56.113
4. REFERENCES TO OTHER APPLICABLE SOPs
This SOP affects all other SOPs.
406 Subject Compensation
1. OBJECTIVE
Research subjects may be offered compensation to offset the time and inconvenience involved in participating in research. Within bounds, it may also serve as an incentive for participation. It is not, however, to be considered a benefit of participation in the research.
There are no specific regulations on compensation other than it may not constitute undue influence or coercion. Investigators and IRB are both responsible to ensure that any compensation provided to subjects is fully disclosed and does not constitute either undue influence or coercion.
Specific Procedures
How subjects may be compensated may take different forms, both monetary and non-monetary. Examples include but are not limited to
- Monetary: cash, gift cards, coupons
- Non-monetary: gift, course credit, extra credit
Compensation may, further, be provided to a subject either directly and indirectly or by means of a drawing.
Both the investigator and the IRB should carefully consider the timing of the compensation. If the research involves a single interaction between the investigator and the subject, compensation should be provided immediately following said interaction or as soon as appropriate thereafter. For research that involves multiple interactions or procedures, providing the compensation at the end of the research may pressure the subject to not withdraw as it is their right – and thus constitute undue influence or coercion. In such cases, compensation should be prorated through the course of the study and provided proportionately throughout the course of the research.
All information regarding compensation must be provided to the subject through the informed consent document and process including but not limited to:
- Amount of compensation
- Timing of compensation
- If a drawing, description of the drawing process and odds of winning compensation
2. SCOPE
The policies and procedures apply to all human subjects research providing compensation to subjects conducted by BYU investigators
3. APPLICABLE REGULATIONS AND GUIDELINES
45 CFR 46.111
4. REFERENCES TO OTHER APPLICABLE SOPs