Dana Evans 1 1 Exempt & Expedited Human Subjects Research

Objectives To know the categories for Exemption and criteria for Expedited Review of human subjects research. 2

Is it Human Subjects Research? 45 CFR (f) Human Subject - a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual, or obtains/use/access identifiable private information 3

Is it Research? 45 CFR (d) A systematic investigation (including research development, testing and evaluation) designed to develop or contribute to generalizable knowledge. 4

Identifiable Private Information Occurs in a context in which an individual can reasonably expect that no observation or recording is taking place. Has been provided for specific purposes by an individual. The individual can reasonably expect will not be made public. The identity of the subject may readily be ascertained by the investigator or associated with the information. 5

Human Research Guiding principle: Belmont Report National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research April 18, 1979 Three Basic Ethical Principles when developing your research protocol: 1. Respect for Persons - Individual autonomy, protect individuals with reduced autonomy 2. Beneficence - Maximize benefits and minimize harms 3. Justice- Equitable distribution of research burden, costs and benefits 6

Human Research Protections Program IRB approval or approval by the EDO must be prospectively obtained prior to the implementation of any proposed research activity involving human subjects, regardless of funding source(including unfunded projects). 7

Human subject protection from research risks – not an issue if risk is minimal Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. 8

Full Board or Expedited Review? Greater than minimal risk – requires full board review Minimal risk - May be exempt from the requirements of IRB review or it may be reviewed via expedited/administrative review procedures. 9

Categories of human subjects research qualifying for IRB Expedited Review procedures 45 CFR ) Clinical studies of drugs and medical devices only when condition (a) or (b) is met. ◦ (a) Minimal risk research on drugs for which an investigational new drug application (21 CFR Part 312) is not required. ◦ (b) Minimal risk 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. 10

Categories of human subjects research qualifying for IRB Expedited Review procedures 45 CFR (cont’d) 2.) Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture as follows: ◦ (a) from healthy, non-pregnant adults who weigh at least 110 pounds. 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 ◦ from other adults and children 2, considering the age, weight, and health of the 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. 11

Categories of human subjects research qualifying for IRB Expedited Review procedures 45 CFR (cont’d) 3.) Prospective collection of biological specimens for research purposes by noninvasive means. Examples: (a) hair & nail clippings in a nondisfiguring manner; (b) deciduous teeth at time of exfoliation or if routine care indicates a need for extraction; (c) permanent teeth if routine care indicates a need for extraction; (d) excreta & external secretions (including sweat); (e) 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; (f) placenta removed at delivery; (g) amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; (h) supra- & subgingival dental plaque & calculus, provided the collection procedure is not more invasive than routine & the process is accomplished in accordance with accepted prophylactic techniques; (i) mucosal & skin cells collected by buccal scraping or swab, skin swab, or mouth washings; (j) sputum collected after saline mist nebulization. 12

Categories of human subjects research qualifying for IRB Expedited Review procedures 45 CFR (cont’d) 4.) Collection of data through noninvasive procedures routinely employed in clinical practice, excluding x-rays or microwaves. Medical devices must be FDA approved (must not intend to evaluate the safety and effectiveness of the medical device for new indications.) Examples: (a) sensors to the body surface or at a distance not involving significant amounts of energy or invasion of the subject’s privacy; (b) weighing/testing sensory acuity; (c) MRI; (d) EKG, EEG, Echo, thermography, detection of naturally occurring radioactivity, electroretinography, infrared imaging, doppler blood flow, (e) moderate exercise, strength testing, body composition, flexibility testing …consider: age, weight, & health of the individual. 13

Categories of human subjects research qualifying for IRB Expedited Review procedures 45 CFR (cont’d) 5. ) Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for non-research 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 (b)(4)45 CFR (b)(4). 14

Categories of human subjects research qualifying for IRB Expedited Review procedures 45 CFR (cont’d) 6.) Collection of data from voice, video, digital, or image recordings made for research purposes. 15

Categories of human subjects research qualifying for IRB Expedited Review procedures 45 CFR (cont’d) 7.) Research on individual or group characteristics or behavior ( 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. 16

Categories of human subjects research qualifying for IRB Expedited Review procedures 45 CFR (cont’d) 8.) Continuing review of research previously approved by the convened IRB: ◦ where (i) the research is permanently closed to enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) research remains active only for long-term follow-up of subjects; or ◦ no subjects have been enrolled and no additional risks have been identified; or ◦ data analysis only 17

Categories of human subjects research qualifying for IRB Expedited Review procedures 45 CFR (cont’d) 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. 18

Exempt Determination Official (EDO) Review and/or concur with submissions pertaining to non-human subjects research determinations and research determined to be exempt from IRB requirements. 19

Categories of human subjects research that may be Exempt from IRB requirements 45 CFR (b) (1) Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as: (i) research on regular and special education instructional strategies, or (ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods. 20

Categories of human subjects research that may be Exempt from IRB requirements 45 CFR (b)(cont’d) (2) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), anonymous survey procedures, interview procedures or observation of public behavior, unless: (i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and (ii) 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. 21

Categories of human subjects research that may be Exempt from IRB requirements 45 CFR (b) (cont’d) (3) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (b)(2) of this section, if: (i) the human subjects are elected or appointed public officials or candidates for public office; or (b)(2) (ii) federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.  22

Categories of human subjects research that may be Exempt from IRB requirements 45 CFR (b) (cont’d) (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. 23

Categories of human subjects research that may be Exempt from IRB requirements 45 CFR (b) (cont’d) (5) Research and demonstration projects which are conducted by or subject to the approval of department or agency heads, and which are designed to study, evaluate, or otherwise examine: (i) Public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs. 24

Categories of human subjects research that may be Exempt from IRB requirements 45 CFR (b)(cont’d) (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. 25

Overlapping Exempt and Expedited Categories EXEMPTKey DifferencesEXPEDITED Category 2: Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless: (i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and (ii) 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. Exemption applies if: -Data is identifiable but not sensitive, or -Data is sensitive but de-identified. -Children are only undergoing educational tests or observation of public behavior without investigator interaction Expedited applies if: -Data is identifiable, sensitive and measures are in place to protect confidentiality -Children are to be surveyed, interviewed, or observed with investigator interaction 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 (b)(2)and (b)(3). This listing refers only to research that is not exempt.) Category 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. Exemption applies if: -All data is existing, and recorded without identifiers or codes Expedited applies if: -Data is existing and identifiers retained, or -Data will be prospectively collected for non-research purposes (identifiers can be kept) Category 5: Research involving materials (data, documents, records, or specimens) that have been collected, or will be collected solely for non-research 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 (b)(4). This listing refers only to research that is not exempt.) 26

Case Scenario Dr. Martin, the Chair of the IRB, plans to survey researchers at his institution to assess satisfaction with the IRB review process. Approximately 50 researchers will be randomly selected to complete an online survey. 27

Exempt Review Dr. Martin and his colleagues at other sites believe there is a correlation between satisfaction with the IRB and departmental support. Each site will send surveys to 50 researchers. The surveys will be anonymous. Key Points: Dr. Martin is engaged in research with human subjects and IRB review is required. Even though the survey may ask sensitive information, he meets Exempt Category 2 because results are recorded without identifiers. 28

Expedited Review Dr. Martin plans to retain identifiers on the surveys so that he can send out a second survey to those researchers who score extremely high on the dissatisfaction scale. Key Points: This project does not qualify for Exempt review due to retention of identifiers. Expedited Category 7 may apply if the IRB reviewer believes there are adequate measures in place to protect confidentiality and the risk is minimal. 29

Case Scenario Dr. Richards has a freezer of blood samples that were originally collected for a research study which ended several years ago. Patient codes (which can be linked to the Medical Record) remain on the samples. The consent form originally signed by the subjects of Dr. Richards indicated whether or not their stored blood could be used for future research. 30

Exempt Review Dr. Richards gives the research the samples with the patient code. The research immediately removes the code upon receipt of the samples. Key Points: Because she is given samples with the patient code, the researcher is engaged in human subjects research. However, Exempt Category 4 applies as she is using existing samples and she plans to immediately remove the patient code. 31

Expedited Review The researcher retains the patient code just in case she needs to contact the patient for follow-up information. Key Points: Exempt Category 4 does not apply as the researcher retains the patient code. The study may qualify for Expedited Category 5 (research involving materials that have been collected), as well as Expedited Category 7 if she eventually contacts subjects for follow-up information. 32

Exempt Determination Official 33

Protect confidentiality by: Eliminate identifiers (“safe harbor method”) Substitute codes for identifiers Encrypting identifiable data Limiting access to identifiable data Secure storage or destruction of paper or electronic records 34

Scenario: Exempt or Expedited? An investigator obtains individually identifiable information on the treatment outcomes of patients treated for arthritis with either Drug A or Drug B by viewing patients’ existing individually identifiable medical records at the clinics where the patients were treated. The investigator records only patient age, sex, diagnosis, treatment, and health status at the end of 6 months of treatment so that the investigator cannot link the recorded information back to the patients. 35

Answer: Exempt In this example, the investigator is conducting human subjects research because the investigator is obtaining identifiable private information from patients’ (and now subjects’) medical records. However, the study would be exempt under 45 CFR (b)(4) since the investigator records the information in such a manner that subjects cannot be identified either directly or indirectly through identifiers linked to the subjects. 36

Scenario: Exempt or Expedited? An investigator obtains individually identifiable information on the treatment outcomes of patients treated for arthritis with either Drug A or Drug B by viewing patients’ existing individually identifiable medical records at the clinics where the patients were treated. The investigator records the patients’ treatment outcomes in a coded manner that could permit the identification of the patients. 37

Answer: Expedited In this example, the investigator is conducting human subjects research because the investigator is obtaining identifiable private information from patients’ (and now subjects’) medical records. The study would not be exempt under 45 CFR (b)(4) since the investigator is recording the information in a coded manner, thus allowing the subjects to be identified indirectly through identifiers linked to the subjects. 38

Thank you for your attention! 39