The Department of Health and Human Services’ Office of Human Research Protections (OHRP) provides a decision tree to help investigators make a decision as to whether human subjects research is eligible for exemption from the human subjects regulations or whether an IRB application is needed. Should any concerns, questions, or doubt arise as to whether an IRB applications is needed, contact the IRB to ensure that the correct decision is made. Only in the most clear-cut cases should an investigator determine that the human subjects research is exempt from the human subjects regulations. Student investigators should consult with their faculty advisor when using the decision tree. If the investigator determines that an IRB proposal is necessary, it is up to the IRB to determine the appropriate level of review. OHRP provides a series of charts to assist researchers in determining the appropriate level of IRB review. See http://www.hhs.gov/ohrp/policy/checklists/decisioncharts.html.
If a determination is made that the human subjects research is exempt from the human subjects regulations, nonetheless, the person or persons making that determination should submit to the IRB a statement sufficiently describing the research and basis for the determination that the research is exempt so that the IRB may review the determination. The Chair of the IRB or his or her designee on the IRB shall conduct this review. The IRB shall respond in writing either approving the determination of exemption from the human subjects regulations or indicating that further information is necessary or that an application to it is necessary. Prior to commencing the research project, the investigator must receive a written response from the IRB.
All applications submitted to the IRB should be carefully prepared. When a student is the principal investigator, the faculty / staff / administrative person advising the student investigator should carefully review the IRB proposal before it is submitted. The IRB will determine what level of review is required for the proposal.
4.1 Exempt Research
4.2 Expedited Review
4.3 Full Reviews
4.4 Re-approval Review
4.5 Expiration of Approval Periods
4.6 Modifications to Currently Approved Research
4.7 Final Report and Notice of Terminated Study
4.8 IRB Appeals Policy
4.9 Conflict of Interest Policy and Disclosures
4.10 HIPAA and the Privacy Rule
4.11 Subaward Agreements with Subcontractors
4.1 Exempt Research
Certain categories of research are exempt from the human subjects regulations when the data collected is not linked or identifiable to participants and any risks present will not cause more than minimal harm or discomfort.
What Exemption Means: "Exemption" as used in this document means exemption from the requirements set forth in the HHS regulations (45 CFR 46), such as the requirement for a written informed consent document. Initial determinations of exemption can be made by investigators using a decision tree provided by OHRP. (See section 4.0)
What Exemption Does Not Mean: "Exemption" does not mean that the research activity is exempt from the laws of the State of Connecticut, and it does not mean that the research need not conform to the canons of sound research ethics.
These exemptions do not apply to research involving prisoners, fetuses, pregnant women, human in vitro fertilization, the mentally disabled, or certain research involving surveys or interviews of children except where the research involves only educational tests and observations where the investigator does not participate in or manipulate the activities being observed.
A determination that research is exempt does not imply that investigators have no ethical responsibilities to subjects in such research; it means only that the regulatory requirements related to IRB review, informed consent, and assurance of compliance do not apply to the research.
Research activities in which the only involvement of human subjects fits one or more of the categories listed below may qualify for exemption from review. These exempt categories do not apply to research involving deception of subjects where the investigator does not disclose the true purpose of the research and/or the results of the subject's participation in the study.
Further, a determination of exemption by an investigator does not necessarily exempt investigators from the requirement of gaining consent or permission from subjects. Most research requires the use of an informed consent document (see Appendix 9 for examples), an approved alteration, a letter of explanation, or specific instructions on how to express consent. For minimal risk studies where there are no subject identifiers (i.e., anonymous data are collected) or where subject identifiers have been decoupled from data that has been collected, an information sheet, cover letter or statement in the introduction to the survey or other instrument may be substituted in place of a written and signed consent form. (See section 5.4 of this manual.)
The following categories of research are exempt from the human subjects regulations. A decision that a particular research protocol is exempt should include documentation indicating the specific category justifying the exemption.
Existing Data, Records or Specimens, Recorded Anonymously
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 .[45 CFR 46.101 (b)(4)]
Existing data means data from publicly available sources or anonymous sources and applies to retrospective studies involving data that has already been collected and is "on the shelf" when the protocol is submitted. The exemption does not apply if some of the data or materials exist, but the research will gather additional data or materials. In addition, the exemption applies only if the data is anonymous or the investigator records the data in such a way that participants cannot be identified. This means that if any codes exist by which participants could be identified, the exemption does not apply.
Personal identifiers linked to participants include names, initials, date of birth, social security numbers, and agency record numbers.
Database files may qualify for exemption if there are procedures in the release of information from the source that prevent identification of individuals. It is not enough that participants are not identifiable in the final publication. Publicly available sources of data include examples such as telephone books and public records. Data bank, archival or other types of organizational records may be exempt depending on the policies and procedures to prevent the release of personal identifiers.
Surveys, Interviews, Public Observations, and Educational Tests
Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless: (a) information obtained 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 . [45 CFR 46.101 (b)(2)]
This exemption is available for research within any of the stated categories involving adults, unless the information is both recorded in such a way that the human subjects can be identified (by links or otherwise) and the disclosure of the subjects' responses outside the research could place the subjects at risk or cause personal harm. Thus, surveys involving sensitive topics (such as drug or alcohol use, sexual habits, detailed health histories, illegal behavior, etc.) where there are codes or other links between the information and the subject are not exempt.
Studies that use interview methodologies may require IRB review if the interview will be published or publicly presented, and individuals could be identified.
Certain educational tests are exempt from the human subjects regulations: tests of knowledge, mastery and skills that do not include individual subject identifiers or ask sensitive information from the subjects.
Observational research involving sensitive aspects of human behavior, or in settings where subjects have a reasonable expectation of privacy, is not exempt.
Sensitive survey research is seldom exempt. A sensitive survey includes questions about illegal activities or highly personal aspects of the subject's behavior, life experiences, or attitudes. Questionnaires or surveys covering sensitive topics, however, may qualify for exemption if they: (a) insure the anonymity of the subject; (b) inform the potential subjects as to the sensitive nature of the topics they will be asked to address; and (c) the study does not exceed minimal risk.
The exemption does not apply to research involving the observation of children, except for research involving observations of public behavior when the investigator does not participate in the activities being observed (i.e., the investigator does not manipulate or influence the observed activities).
Research under this category that would not otherwise be exempt may qualify for exemption if: (a) it involves elected or appointed public officials or candidates for public office (for example, surveys, interviews or observation of public officials or candidates for public office); or (b) federal statute requires without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter. [45 CFR 46.101 (b) (3)].
Educational Settings and Normal Educational Practices
Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (a) research on regular and special education instructional strategies, or (b) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods. [45 CFR 46.101 (b)(1)]
To qualify for exemption under this category, all of the research must be conducted in a commonly accepted educational setting and should not involve sensitive topics (e.g., sexual behavior, drug abuse, personal issues) nor increase the level of risk or discomfort beyond normal, routine educational practices. Provisions should be made to insure the existence of a non-coercive environment for all students, including those who choose not to participate. Written permission of the school or appropriate agency should be obtained prior to the implementation of the research, including review of the proposed study by the human subjects research office or committee as applicable to or required by each school site.
Public Benefit Service Programs, Taste and Food Quality Studies
Also exempt are research and demonstration projects which are conducted by or subject to the approval of department and agency heads and which are designed to study, evaluate, or otherwise examine public benefit or service programs; procedures for obtaining benefits or services under those programs; possible changes in or alternatives to those programs or procedures; or possible changes in methods or levels of payment for benefits or services under those programs [45 CFR 46.101(b) (5)].
The federal regulations also exempt taste and food quality evaluation and consumer acceptance studies if (a) wholesome foods without additives are consumed, or (b) a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe by the FDA or approved by the EPA or the Food Safety and Inspections Service of the USDA [45 CFR 46.101 (b) (6)].
4.2 Expedited Review
Research Categories Eligible for Expedited Review
The categories eligible for expedited review include a number of specific examples approved by the Secretary of the Department of Health and Human Services as published in the Federal Register.
Among others (mostly medical devices or clinical studies of drugs), research activities that may be accepted by the IRB for expedited review include research involving materials (data, documents, records, or specimens) that have been collected or will be collected solely for non-research purposes or collection of data from voice, video, digital, or image recordings made for research purposes;
- 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 (some research in this list may be eligible for exemption);
continuing review of research previously approved by full review of the IRB where the research is permanently closed to the enrollment of new subjects, all subjects have completed research-related interventions, and the research remains active only for long-term 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.
For the full list and additional guidance on the categories of research eligible for expedited review, see the HHS document "Categories of Research That May Be Reviewed by the Institutional Review Board (IRB) through an Expedited Review Procedure" (available at http://www.hhs.gov/ohrp/policy/expedited98.html).
The IRB may use the expedited review procedure to review either or both of the following: (1) some or all of the research appearing on the HHS list and found by the reviewer(s) to involve no more than minimal risk; and (2) minor changes in previously approved research during the period (of one year or less) for which approval is authorized. Under an expedited review procuedure, the review may be carried out by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among the members of the IRB. In reviewing the research, the reviewers may exercise all of the authorities of the IRB except that the reviewers may not disapprove the research. (A research activity may be disapproved only after a full review.) The IRB shall adopt a method for keeping all members advised of research proposals that have been approved under the expedited procedure.
4.3 Full Reviews
Most applications submitted to the Trinity College IRB qualify for either exemption or expedited review. Research that does not qualify for exemption or expedited review must undergo a full IRB review by a quorum of IRB members at a convened meeting. (A quorum consists of a majority of the members of the IRB, including at least one member whose primary concerns are in nonscientific areas.) The application process and forms remain the same as for the other levels, but a full review may take longer after receipt of a complete, signed application. In the event that no additional information, clarifications or modifications are requested, the IRB may approve a study within a short time period, but the initial full review process often does not result in an outright approval of the research. Minor or major revisions and written clarifications may be requested, adding time to the review process.
In a Full Review, the IRB performs a detailed examination of the review application and all supporting documentation, including the proposed informed consent form and any recruitment materials, questionnaires, or survey instruments.
IRB members with a potential conflict of interest in any review must recuse themselves from voting and participation in the review, except to provide information requested by the IRB. These disclosures should be stated prior to the agenda item where the protocol is presented for discussion. After a full discussion of the complete application, the IRB Chair calls for a vote. Results of IRB decisions are then communicated in writing to the investigator and Trinity College. This letter will justify any conditions required for final approval, may request additional information or revisions, and will indicate the next steps in the review process, if any.
The IRB may come to one of five determinations:
1. Unconditional Approval: Approval of the study as submitted without questions or clarifications (in order for research to be approved, it must receive the approval of a majority of those IRB members present at the meeting);
2. Approval with Stipulations: Acceptance of the protocol with requests for clarification and/or revisions (minor changes that can be reviewed and accepted by the Chair, a designated IRB member with relevant expertise, or a subcommittee of the IRB);
3. Deferred Approval: Deferral of the application pending written responses to major or substantive questions raised by the IRB during the initial review (requires convening of the full IRB for a second deliberation meeting);
4. Tabling: Approval is not granted until further information is provided or specific changes are made. When new information is submitted, the protocol is reviewed again by the full IRB.
5. Disapproval: Disapproval of the research application (the study cannot be conducted) with the right of appeal. Investigators have the right to discuss any of the IRB outcomes directly with the Chair. In the case of disapproval, the letter of determination will include specific reasons for the disapproval with provision of an opportunity for reply and appeal by the investigator. The reply can be in writing or in person at a convened meeting of the IRB, or both. In the end, the IRB retains final authority for approval of proposed research involving human subjects.
All meetings of the IRB are documented in written minutes to include an agenda of topics; attendance at the meeting; protocols reviewed; actions taken by the IRB; the vote on these actions, including the number of members voting for, against, and abstaining; reasons for requiring changes or disapproving, suspending, or terminating research; and a written summary of the discussion of controverted issues and their resolution. These minutes are available for review and action by IRB members at subsequent meetings. When approved in final form, the minutes are available for review by the Dean of the Faculty, the signatory official for human subjects research at Trinity, the President of Trinity College, and the Trinity College legal counsel.
4.4 Re-approval Review
Research/study proposals that have been determined to be exempt from review do not need to be submitted for re-approval or continuation review as long as no changes or modifications that will no longer qualify the study for an exemption are contemplated by the investigator. Any substantive departures from or changes to the exempted procedures must be submitted to the IRB as modifications and could result in an upgrading of the study by the IRB to that of an Expedited or Full Review. However, if the research has been conducted according to the initial exemption, the investigator should submit only a Final Report Form upon completion of the study.
Approvals under the expedited and full review categories, on the other hand, are granted by the IRB for not more than one year. Federal regulations require the IRB to conduct "continuing review" of ongoing research, including multi-year studies, no less than annually. The IRB sets the next review date at the time of initial approval based primarily on the degree of risk of the study: the higher the risk, the earlier the IRB may set the expiration date of the initial approval. Other factors include the nature of the study and the vulnerability of the subject population. The IRB notifies the investigator of the expiration date for "re-approval," and a reminder notice is sent to the investigator at least one month in advance of the actual date.
To apply for continuation of the research, the investigator submits an IRB Progress Report requesting re-approval. By completing this report the investigator also informs the IRB of the status of the research project:
The IRB Progress Report must be signed by the principal investigator certifying that the study will continue to be carried out as described in the re-approval application and in accordance with the research ethics, norms and standards in the respective discipline. In the case of student research, the responsible faculty member must approve and sign the re-approval application.
Conflict of interest forms must also be submitted with the re-approval application for all investigators, whether continuing or new investigators, who fit the definition of investigator in the Trinity College Conflict of Interest policy.
Projects that initially required full IRB review most often will require full IRB re-approval review unless the project qualifies for an expedited review for one of the following reasons: no changes have been instituted or are contemplated since the initial review; the changes are minor or administrative in nature; the research is closed to the enrollment of new participants; all participants have completed research interventions, and the research remains active only for long-term follow-up of participants; no participants have been enrolled and no additional risks have been identified; or where the remaining activities are limited to data analysis.
4.5 Expiration of Approval Periods
When continuing review of research does not occur prior to the end of the approval period specified by the IRB, the IRB approval expires automatically. Failure to either close a study or apply for re-approval prior to the expiration date constitutes non-compliance.
Under any of the review categories, if the ending date expires prior to submission of the re-approval application, the investigator must suspend participant contact and all data collection until the re-approval is obtained from the IRB. The investigator with an expired protocol may be subject to a protocol audit and may be required to submit an application for review and approval as a new study. No new participants may be contacted, recruited, or enrolled during the interim period, and if data has been collected, the data cannot be used in the study. If the study is formally completed, terminated, or cancelled, the investigator must submit a Final Report Form so that the study file may be closed permanently.
4.6 Modifications to Currently Approved Research
Modifications to currently approved protocols, research instruments, or the informed consent process must be submitted to the IRB for review and approval prior to implementation. Minor changes that do not increase the risk to participants may receive an expedited review per the eligibility criteria established for the continuation of expedited review studies (see section 4.2).
Modifications that increase the risks to GREATER than minimal are forwarded to the full IRB committee for review.
Changes to approved protocols cannot be implemented prior to IRB review and approval except when necessary to eliminate apparent immediate hazards to a subject.
Any unanticipated risks to subjects, emergency changes in procedures, adverse events, or instances of noncompliance with college, state or federal regulations must be reported immediately to the IRB for appropriate and timely resolution.
Investigators may request modifications to currently approved research by submitting an IRB Progress Report. Modifications can be requested at any time or along with requests for re-approval if a study is about to expire. In Section F of the IRB Progress Report, investigators can specify the proposed modification(s) in terms of participant enrollments, instruments, or any proposed changes in the scope of the project, research methods, risks and benefits, or informed consent, as applicable. Changes in the risks, benefits, or research procedures may require modifications to the consent form and may, in some cases, warrant the re-consenting of participants already in the study. Revised consent forms that are proposed for use must be submitted with the modification request.
The date of approval of the modification does not change the date by which the regularly scheduled re-approval review of the project is to be completed. If a modification involves the changing of principal investigator(s), a letter from the original investigator indicating the need for the change plus a letter from the new investigator accepting responsibility for the research or study should be included along with the modification. In the case of addition or deletion or any assistant investigators, the principal investigator should inform the IRB in Section C of the IRB Progress Report.
Conflict of interest forms must be submitted for all new investigators.
4.7 Notice of Terminated Study
The IRB may issue a Notice of Terminated Study independently under a number of circumstances such as:
1. the study approval period has expired without an application from the investigator for re-approval or to close the study;
2. serious violations of IRB or federal compliance rules for the protection of human subjects;
3. unauthorized use of consent forms without notification to the IRB; or
4. audit findings that warrant termination of a study.
4.8 IRB Appeals Policy
Any decision, review outcome, or audit finding may be appealed to the IRB. Investigators must submit their appeal in a letter to the IRB Chair outlining the reasons for the appeal and why the IRB decision, review or audit outcome should be reconsidered. If the appeal involves a relatively minor request, the Chair or a subcommittee of the IRB may consider the issue and reach an equitable determination. However, appeals of expedited and full review outcomes or any other substantive matters such as audit findings must be reviewed and decided by the full IRB at a convened meeting. The investigator may request to be present at the meeting or may be invited to do so by the IRB to clarify any issues pertinent to the written appeal. After presentation of the information and review of the documents, the full IRB will vote to approve or not approve the appeal. The decision of the IRB will be final.
4.9 Conflict of Interest Policy and Disclosures
Conflicts of interest may occur when an investigator's research responsibilities compete with his or her private interests, such as financial interests, raising concerns of objectivity and improper gain. Conflicts of interest may exist despite the highest standards of conduct and candor. Fortunately, most conflicts can be successfully resolved and managed without impeding research activities.
Trinity College Policy on Conflict of Interest Pertaining to Sponsored Projects [link to come]
Trinity College Employee Affirmation Pertaining to Conflict of Interest [form under construction]
Trinity’s policies and rules concerning potential conflicts of interest and disclosures also apply to IRB members when they are assigned protocol applications for review. Each IRB member should consider possible or potential conflicts of interest and determine whether a particular role or relationship could affect his or her objectivity before reviewing, participating in a protocol discussion, or voting on a protocol application. Possible relationships to consider include: the IRB member is a listed investigator or advisor on an application; the member has a familial or close personal relationship with the investigator; the member holds a financial interest in the outcome of the research; or other concerns that warrant abstaining from review, deliberation and voting on a protocol.
In the event of a potential conflict of interest the IRB member should not accept the protocol for review and should return the application for assignment to another member; or at full review meetings, any member(s) should disclose conflicts or simply state that participation is not appropriate and then recuse themselves from discussion and voting on the protocol.
4.10 HIPAA and the Privacy Rule
The Health Insurance Portability and Accountability Act (HIPAA) protects the confidentiality of individually identifiable health information maintained or transmitted by a covered entity in any form or medium, including: demographic information; medical history; information relating to the past, present or future physical or mental health or condition of an identifiable individual; the provision of health care to an individual or the payment for the provision of health care; physical examinations, blood tests, or x-rays; and other diagnostic and medical procedures.
Privacy standards within HIPAA limit the use and disclosure of health information; restrict most disclosures to the minimum intended purpose; establish new requirements for access to records by researchers; and protect the confidentiality and integrity of health information.
Research protocols, which include the gathering of health or mental health information and are submitted in accordance with HIPAA’s privacy standards, restrictions and other requirements, must develop and submit a HIPAA Authorization form that contains core elements in the HIPAA Privacy Rule: description of the information to be used or disclosed; identification of the persons or class of persons authorized to make the use or disclosure of the protected health information; identification of the persons or class of persons to whom the covered entity is authorized to make the use or disclosure; and expiration date or event; the individual's signature and date; and, if signed by a personal representative, a description of his or her authority to act for the individual.
For more information and templates go to the HIPAA web page (http://privacyruleandresearch.nih.gov/authorization.asp).
4.11 Subaward Agreements with Subcontractors
For research projects and studies involving subcontractors or other subrecipients, Trinity College policy requires documentation and monitoring of human subjects compliance by way of specific language to be contained in all Subaward Agreements. Research investigators at Trinity College should contact the director of faculty grants and sponsored research (Office of College Advancement) to determine if subawards or subcontracts involving human subjects research conform to College policy.