What is “Exempt” Human Subject Research, And What Does It Mean? (2019 Edition)

March 2019 Issue

(Note: this article is an update of an article with the same name published in April 2017)

Author(s):

  • Fanny K. Ennever, PhD
    Research Compliance Officer, Boston Medical Center

  • Matthew Ogrodnik, MS, CIP
    IRB Director, Boston Medical Center and Boston University Medical Campus

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WHAT IS “EXEMPT” HUMAN SUBJECTS RESEARCH, AND WHAT DOES IT MEAN?

Briefly, research is termed “Exempt” when it constitutes research with human subjects, but ALSO meets the requirements of a defined low-risk category that is exempt from SOME (but not all) of the requirements governing human subjects research.

 

To qualify as Exempt, the research must:

  • NOT be a clinical investigation of a drug, device, or other product regulated by the Food and Drug Administration; and
  • Pose no greater than minimal risk to the subjects; and
  • Fit into a defined Exempt category:
    • One of the eight Exempt categories defined by the Common Rule (Code of Federal Regulations Title 45 Part 46 – abbreviated 45 CFR 46) – regardless of the source of funding; or
    • One of the five additional Exempt categories defined locally with our “Equivalent Protections” policies – only for research with no external funding.

This article focuses on the Exempt categories most commonly used at BMC/BU.   The full listing of the eight federal Exempt categories and the five additional Exempt categories under Equivalent Protections can be found at the end of this article.

Educational Research

Exempt educational research falls into Exempt Category 1 (any funding), if it is conducted in an educational setting and involves normal educational practices. You must describe in your application why you think the research is not likely to adversely impact the students’ opportunity to learn required educational content. Typical studies include research on instructional strategies, and on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

Surveys and Interviews

Surveys and interviews fall into Exempt Category 2 (any funding) if all subjects are adults, or Exempt Category 12 (no external funding) if some subjects are children.

For surveys and interviews with adults (including focus groups, which are group interviews), there are two choices in the INSPIR application. Category 2.1 is selected when the information will be anonymous; that is, no one will ever know the identity of the subjects. Category 2.2 is selected when the information will be identifiable; in which case, the information must be adequately protected against disclosure. The IRB will conduct a “limited IRB review” of the privacy and confidentiality protections to make this exemption determination. This does not change anything for researchers, however, because the IRB conducts this review based on the privacy and confidentiality information we already ask you to detail in the INSPIR application.

For surveys and interviews with children (Exempt Category 12), a parent or guardian must provide permission for their children to participate. Surveys and interviews with children can still be done in studies with external funding, but will follow the Expedited approval pathway instead of the Exempt pathway.

Benign Behavioral Interventions

To qualify for Exempt Category 3 (any funding), benign behavioral interventions must be brief, harmless, painless, not physically invasive, not likely to have a negative lasting impact on the subjects, and not reasonably considered offensive or embarrassing. Another qualification for this category is that participants must prospectively agree to participate in the study. There is one carve-out for studies involving deception:  If you inform the participant(s) up front that he/she will be deceived about the true purpose of this study, and the participant agrees to take part after being informed of the deception, then the study can be determined to be exempt under Category 3.

Similar to surveys and interviews, INSPIR has two choices. Category 3.1 is selected when the participants will be truly anonymous (not very likely for this type of study), and Category 3.2 is selected otherwise. Again, the study must include adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data. The IRB will make this determination about the privacy and confidentiality protections based upon the information collected in the INSPIR application.

Data/Specimen Analysis Research

A study consisting of analyzing data or specimens only, and not involving any interventions or interactions with subjects to collect those data or specimens, is most likely to be exempt if it is not externally funded. Of the three categories listed below, only the first is available for externally-funded research, and it is quite restrictive. Again, this does not mean such research cannot take place; only that the IRB will provide Expedited approval instead of an Exempt determination.

Anonymous use of data/specimens

This category, Exempt Category 4, is the only one available for externally-funded data/specimen analysis research. To qualify, all the information must be recorded by the investigator in such a manner that subjects cannot be identified; the investigator must not contact the subjects; and the investigator will not re-identify subjects. In addition, at no point will a master code (link between a subject's identifiable data such as medical record number or name and the data set) be created even momentarily; the Subject ID will never be located along side of any identifiable data such as a name or medical record number; and all data for each subject will be collected in one sitting and the medical record number will not be retained once the data is collected.

The classical example of research that would be exempt under this category would be someone who pulls a number of medical record charts, then sits down and records a list of data points of interest onto a data collection form, making sure not to include the name, address or medical record number of the patient on the form.  With the advent of electronic medical records, the data may be housed in multiple online databases. Often, for research that involves collection of data from multiple sources, the easiest way to do this is to link the identifiable data (such as medical record number) with a unique study ID via a “master key.”  This type of coding, however, means that the research is not exempt under Category 4. In order for a medical record review research project to qualify as exempt under Category 4, the subject identifiers can never be linked to the research dataset.  However, the researcher may have access to a temporary list of identifiers that are crossed off one-by-one as the data are abstracted into the data collection forms/spreadsheet. For this reason, the data for each individual subject needs to be collected in a single sitting.

The revisions to the Common Rule did add a new exemption option under Category 4, but it can only be used if the information accessed is never disclosed outside of the covered entity (BMC or BU GSDM, depending on the source of the medical records). We, therefore, do not use this category at BMC/BU Medical Campus because study teams often include both BMC and BU Medical Campus personnel; and it is too difficult to parse out who can and cannot have access to the information. The vast majority of chart review studies are unfunded and, therefore, qualify for Category 9; so not using this exemption does not have much of an effect on researchers.

Very few externally-funded studies qualify for Exempt Category 4, but again, such studies can be approved by Expedited review.

Identifiable use of non-research data/specimens

This Exempt Category 9 is only available for studies without external funding; and is for research involving materials (data, documents, records, or specimens) that have been or will be collected solely for non-research purposes (such as medical treatment or diagnosis). Most chart reviews (without external funding) qualify for Exempt Category 9.

 Identifiable use of existing research data/specimens

This Exempt Category 10 is also only available for studies without external funding; and is for studies involving data or specimens that have been collected as part of a research study. The IRB can grant this exemption as long as the consent for the research does not preclude such additional research.

A typical example of this type of research would be going into the study records or using study samples to investigate a hypothesis that was not part of the original research. Such studies would qualify for Exempt Category 10 unless the original study consent form had a statement such as: “Your data and specimens will only be used for the research described in this consent form and will not be shared with anyone outside the research team.”

Quality Improvement Research

This Exempt Category 11 is only available for research without external funding. Studies typically fall into this category when the study team would like to analyze data (collected as part of a QI/QA project that is not human subjects research) for research purposes, as well as for QI/QA purposes. In order to qualify, the project must meet the following six criteria:

  1. All patients who get an intervention are expected to benefit; and
  2. All measurements that are collected are to determine the effect of the process change; and
  3. All patients involved in the intervention receive standard care at a minimum; and
  4. The intervention meets evidence-based or consensus-based quality standards; and
  5. Confidentiality protections are appropriate to the sensitivity of the data collected; and
  6. Obtaining consent from the patients is not practicable because the change or intervention will be carried out in a clinical setting where there is no meaningful way for patients to opt out of receiving the intervention.

An example of this type of exempt study would be the implementation of a new checklist in the Emergency Department (ED) designed to improve patient care. Through a medical record review, the study team might want to compare the length of stay of patients from one year prior to the implementation, as compared to one year post-implementation. If the only focus of this project is improving the quality of care in the ED specifically, then this would not normally need to be submitted to the IRB as it is not research; however, if the group also wishes to analyze these results for research purposes, then this project could be submitted for exemption under Category 11 if it has no external funding.

Minimal Risk Research without External Funding

If your research is no greater than minimal risk, has adults able to provide consent as subjects, and does not have external funding, it can likely be given an exemption under Exempt Category 13 if it does not fall into one of the other exempt categories. Be sure to explain why you think the research is no greater than minimal risk in the INSPIR application.

 

WHO DETERMINES WHETHER A PROJECT IS EXEMPT HUMAN SUBJECTS RESEARCH?

IRB Analysts are responsible for making the determination about whether a project meets one of the Exempt criteria. Applicants indicate that they think that their project qualifies as Exempt in the Review Path Determination screen of the INSPIR application (Section 4.1). In addition, there is a special review path for chart reviews.

If the applicant chooses Exempt, then the next screen lists thirteen Exempt categories. The applicant selects the one or more categories which best fits the proposed research; and answers additional questions about the project, including uploading any questionnaires, surveys, data collection tools, etc., so that the IRB Analyst can make the correct determination.

If the applicant chooses chart reviews, then the next questions clarify whether the project qualifies for Exempt Category 4, Exempt Category 9, or neither.  Additional questions gather the appropriate information, including eligibility for a waiver of HIPAA authorization.

 

IS A CONSENT FORM REQUIRED?

The Common Rule requirement for a consent form does not apply to Exempt research.  However, our local HRPP Policies and Procedures requires that there still be a consent process in any Exempt Human Subject Research that involves direct interaction with subjects.  The elements that need to be covered in this process are:

  • that this is a research study; and
  • that participation is voluntary; and
  • the purpose; and
  • what the subjects are being asked to do; and
  • confidentiality protections; and
  • how long participation is expected to take; and
  • a disclosure if the subject will be audio- or video-taped; and
  • how to contact an investigator or research staff member for questions about the study.

There is no requirement for a signature, and no requirement that this information be given in writing.  The elements can be included as part of an on-line survey, as a written sheet that is given to participants, or it can be delivered orally.  If it is delivered orally, you should, as a courtesy, provide the subject with the PI’s name and contact information in a written format (e.g., handing them a business card). The Exempt Information Sheet Template on the IRB website should be downloaded, customized for the study, and submitted with the IRB application.

If the study involves interaction with subjects, then the plans for conducting the consent process--along with either a script (if orally), a written sheet, or the questionnaire that includes this information--must be included in the IRB application.

 

WHAT DO I HAVE TO DO AFTER A PROJECT IS DETERMINED TO BE EXEMPT?

Exempt determinations are given a status check-in date that is three years from the date of the initial Exempt determination. If during this three-year period you make changes to your project that may affect the Exempt determination, then you will need to submit an amendment through INSPIR.  Minor changes, such as changes to wording on a questionnaire, do not require submission of an amendment.  If, however, you are changing the types of questions you are asking (such as more sensitive questions that are not anonymous), then you are required to submit an amendment.  Three years after the Exempt determination, you will receive a request to fill out a brief status check-in form that includes questions  about the status of the study; and a request to detail the changes, if any, that have been made to the study since the time of initial review by the IRB. You will indicate whether you wish to close the study or renew your Exempt determination for another three years.

Also, during the course of the study, you are required to submit Internal Study Personnel Change forms in order to add new engaged study personnel, or remove personnel who are no longer working on the study. These forms must be approved by the IRB before the new personnel can take part in any research activities. This is because the IRB is required to check that all investigators are up to date with all training requirements for both exempt and non-exempt research.

 

SUMMARY

For studies without external funding, most low-risk research can qualify for an Exempt determination. For studies with external funding, they must fit into one of the Common Rule Exempt categories to follow the Exempt pathway; otherwise, they will likely get Expedited approval. It is important to answer the questions carefully in INSPIR to provide the IRB with the information needed to determine the correct review pathway for your study.

 

APPENDIX

The Eight Common Rule Exempt Categories
[Note:  The IRB does not use (2)(ii), 3(ii), 4(ii), 4(iii), 7, or 8.]

  1. Research, conducted in established or commonly accepted educational settings, that specifically involves normal educational practices that are not likely to adversely impact students' opportunity to learn required educational content or the assessment of educators who provide instruction. This includes most research on regular and special education instructional strategies, and research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

  2. Research that only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior (including visual or auditory recording) if at least one of the following criteria is met:

    (i) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;

    (ii) Any disclosure of the human subjects' responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, educational advancement, or reputation; or

    (iii) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by §46.111(a)(7).

  3. (i) Research involving benign behavioral interventions in conjunction with the collection of information from an adult subject through verbal or written responses (including data entry) or audiovisual recording if the subject prospectively agrees to the intervention and information collection and at least one of the following criteria is met:

    (A) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained, directly or through identifiers linked to the subjects;

    (B) Any disclosure of the human subjects' responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, educational advancement, or reputation; or

    (C) The information obtained is recorded by the investigator in such a manner that the identity of the human subjects can readily be ascertained, directly or through identifiers linked to the subjects, and an IRB conducts a limited IRB review to make the determination required by §46.111(a)(7).

    (ii) For the purpose of this provision, benign behavioral interventions are brief in duration, harmless, painless, not physically invasive, not likely to have a significant adverse lasting impact on the subjects, and the investigator has no reason to think the subjects will find the interventions offensive or embarrassing. Provided all such criteria are met, examples of such benign behavioral interventions would include having the subjects play an online game, having them solve puzzles under various noise conditions, or having them decide how to allocate a nominal amount of received cash between themselves and someone else.

    (iii) If the research involves deceiving the subjects regarding the nature or purposes of the research, this exemption is not applicable unless the subject authorizes the deception through a prospective agreement to participate in research in circumstances in which the subject is informed that he or she will be unaware of or misled regarding the nature or purposes of the research.

  4. Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens, if at least one of the following criteria is met:

    (i) The identifiable private information or identifiable biospecimens are publicly available;

    (ii) Information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects;

    (iii) The research involves only information collection and analysis involving the investigator's use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164, subparts A and E, for the purposes of “health care operations” or “research” as those terms are defined at 45 CFR 164.501 or for “public health activities and purposes” as described under 45 CFR 164.512(b); or

    (iv) The research is conducted by, or on behalf of, a Federal department or agency using government-generated or government-collected information obtained for nonresearch activities, if the research generates identifiable private information that is or will be maintained on information technology that is subject to and in compliance with section 208(b) of the E-Government Act of 2002, 44 U.S.C. 3501 note, if all of the identifiable private information collected, used, or generated as part of the activity will be maintained in systems of records subject to the Privacy Act of 1974, 5 U.S.C. 552a, and, if applicable, the information used in the research was collected subject to the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq.

  5. Research and demonstration projects that are conducted or supported by a Federal department or agency, or otherwise subject to the approval of department or agency heads (or the approval of the heads of bureaus or other subordinate agencies that have been delegated authority to conduct the research and demonstration projects), and that are designed to study, evaluate, improve, or otherwise examine public benefit or service programs, including 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. Such projects include, but are not limited to, internal studies by Federal employees, and studies under contracts or consulting arrangements, cooperative agreements, or grants. Exempt projects also include waivers of otherwise mandatory requirements using authorities such as sections 1115 and 1115A of the Social Security Act, as amended.

  6. Taste and food quality evaluation and consumer acceptance studies:

    (i) If wholesome foods without additives are consumed, or

    (ii) If a food is consumed that contains a food ingredient at or 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 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.

  7. Storage or maintenance for secondary research for which broad consent is required: Storage or maintenance of identifiable private information or identifiable biospecimens for potential secondary research use if an IRB conducts a limited IRB review and makes the determinations required by §46.111(a)(8).

  8. Secondary research for which broad consent is required: Research involving the use of identifiable private information or identifiable biospecimens for secondary research use, if the following criteria are met:

    (i) Broad consent for the storage, maintenance, and secondary research use of the identifiable private information or identifiable biospecimens was obtained in accordance with §46.116(a)(1) through (4), (a)(6), and (d);

    (ii) Documentation of informed consent or waiver of documentation of consent was obtained in accordance with §46.117;

    (iii) An IRB conducts a limited IRB review and makes the determination required by §46.111(a)(7) and makes the determination that the research to be conducted is within the scope of the broad consent referenced in paragraph (d)(8)(i) of this section; and (iv) The investigator does not include returning individual research results to subjects as part of the study plan. This provision does not prevent an investigator from abiding by any legal requirements to return individual research results.

The Five Additional “Equivalent Protections” Exempt Categories – for research with no external funding

  1. Research involving the study of materials (data, documents, records, or specimens) that have been or will be collected solely for nonresearch purposes.

  2. Research involving the study of materials (data, documents, records, or specimens) that have been collected for research purposes when the consent for the research does not preclude such additional research.

  3. Research involving Quality Improvement/Quality Assurance where:

    1. All patients who get an intervention are expected to benefit; and
    2. All measurements that are collected are to determine the effect of the process change; and
    3. All patients involved in the intervention receive standard care at a minimum; and
    4. The intervention meets evidence-based or consensus-based quality standards; and
    5. Confidentiality protections are appropriate to the sensitivity of the data collected; and
    6. Obtaining consent from the patients is not practicable because the change or intervention will be carried out in a clinical setting where there is no meaningful way for patients to opt out of receiving the intervention.

  4. Research with children involving survey procedures, interview procedures, or observation of public behavior where the investigators or research staff participate in the activities being observed.

  5. Minimal risk research without external funding with adult subjects able to provide abbreviated consent where the research does not qualify for Categories (9) through (12).