Apr 27, 2016 - new study review. â One business day turnaround for complete new site submissions. â Dedicated stream
April 27, 2016
Determining the Review Level: Non-Human Subject Research, Exempt or Expedited Andrea Bidwell, MSN, RN, CIP IRB Member, Schulman IRB
About Schulman IRB
Established in 1983 Superior audit history with FDA—five consecutive audits with no findings 21 CFR Part 11 compliant electronic systems Compliant with FDA, OHRP and Health Canada requirements Full Board meetings five days a week Dedicated daily expedited review of qualifying minimal risk protocols
About Schulman IRB
Review outcome provided within one business day of new study review One business day turnaround for complete new site submissions Dedicated streamlined processes tailored to Phase I timelines Expert oncology IRB members experienced in all phases of oncology research ̶ National IRB for Cancer MoonShot 2020 initiative
Customized services for institutions Experienced primary points of contact for sponsors, CROs, institutions and sites
About Schulman IRB
Clinical Quality Assurance (CQA) and Human Research Protection (HRP) consulting services provided by Provision Research Compliance Services
www.provisionrcs.com
schulmanirb.com
About Today’s Presenter Andrea Bidwell, MSN, RN, CIP IRB Member, Schulman IRB
Master of Science Degree in Nursing specializing in Neurology and Neurosurgery Schulman IRB and Scientific Board Member since 2013 Primary reviewer for Minimal Risk Review (MRR) service Co-chair of the Schulman Board Education Committee: responsible for executing educational and professional development programs for current IRB and staff members
Objectives
Objectives
Define a step-wise process and a set of criteria for determining whether an activity is research according to the existing DHHS regulations 45 CFR 46 Review the existing definitions under the Common Rule 45 CFR 46 ̶ Research ̶ Human subject research ̶ Not human subject research ̶ Exempt research ̶ Expedited research
Objectives
Discuss examples of research that fall within each review level Describe select elements of the NPRM’s proposed Common Rule changes and the implications for human subject research review
Definitions
Levels of Review – Step 1 Full Board Step 5
Expedited? Step 4
Exempt? Step 3
Human Subject? Step 2
Research? Step 1
Does the Activity Involve Research? – Step 1
Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Based on 45 CFR 46.102(d)
What Is a Systematic Investigation?
An activity that is methodologically driven
Involves a prospective plan
Has a hypothesis
Data or information is collected in an organized and consistent way
The data or information is analyzed in some way
Conclusions can be drawn from the results
Note
OHRP does not consider intent to publish to be a reliable indicator of whether an activity involves research or not. Publication alone does not make it “research.”
Is It Research? – Step 1
Does the activity involve research? ̶ If yes, proceed to step 2. ̶ If no, 45 CFR part 46 does not apply to the activity.
?
Case Study #1
A researcher at a radiology clinic uses a database to help monitor and forecast radiation dosimetry. This practice has been demonstrated to reduce over-exposure incidents in patients having multiple procedures. Patient data are collected from medical records and entered into the database.
The database is later analyzed to determine if over-exposures have decreased as expected. Does this proposed project meet the definition of “research”?
Case Study #1 No.
Such activities do not satisfy the definition of “research” under 45 CFR 46.102(d), which is “…a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge….”
This is an internal quality improvement activity, and the HHS regulations do not apply.
Levels of Review – Step 2 Full Board Step 5
Expedited? Step 4
Exempt? Step 3
Human Subject? Step 2
Research? Step 1
Does the Activity Involve Human Subjects? – Step 2 Definition: Human Subject means a living individual about whom an investigator conducting the research obtains: 1) Data for research purposes through interventions (e.g., venipuncture, biopsy, LP…) or interaction (i.e., interpersonal contact with the individual) AND/OR 2) Accesses and uses identifiable private information (e.g., medical record) where the identity of the subject is or may be readily ascertained with minimal effort by the investigator
Based on 45 CFR 46.102(d)(f)
Does the Activity Involve Human Subjects? – Step 2
Does the activity involve human subjects? ̶ If yes, proceed to step 3. ̶ If no, 45 CFR part 46 does not apply to the activity.
?
Activities that do not meet the definitions of human subjects research need not be reviewed by the IRB.
The IRB can help investigators make this determination.
Case Study #2
Blood samples were obtained for research purposes, with informed consent of the subjects, and the original study has been completed. The samples remain under the control of the original investigator.
Another investigator wants to use a portion of the remaining samples to perform research unrelated to the original study. The sample is identifiable to the secondary user.
Is this considered to be human subjects research under the purview of the IRB?
Case Study #2 Yes.
Step 1 – Is this research? ̶ Yes, investigator wants to use samples to perform research.
Step 2 – Does it involve human subjects? ̶ Yes, access identifiable samples.
Levels of Review – Step 3 Full Board Step 5
Expedited? Step 4
Exempt? Step 3
Human Subject? Step 2
Research? Step 1
Is the Research Exempt? – Step 3
“Exempt” means the research is exempt from the regulations at 45 CFR 46. ̶
Not necessarily exempt from review
Exemptions can only be used for research that is no more than minimal risk. Definition: Minimal Risk means that 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. Note: Research cannot be exempt in any category if research involves prisoners.
Exempt Categories – Step 3 Normal education practices and settings
1.
Research is not FDA-regulated Examples: Evaluating standardized tests, comparing a curriculum ̶ ̶
Educational tests, surveys, interviews or observations unless identifiable and risky
2.
Research is not FDA-regulated Standardized educational tests may include children Category may apply to research with children when investigator observes public behavior but does not interact ̶ ̶ ̶
Identifiable subjects if public officials or if the confidentiality is maintained after the statute
3. ̶
Research is not FDA-regulated
Based on 45 CFR 46.101(b)
Exempt Categories – Step 3 Existing data, documents, records, pathological specimens, or diagnostic specimens if public OR recorded without identifiers
4.
Most commonly used category and is not FDA-regulated Examples: Analyzing existing tissue samples or data recorded by investigators without identifiers ̶ ̶
Public benefit or service programs
5.
Research is not FDA-regulated ̶
Taste/ food quality evaluation
6. ̶
Research is regulated by the FDA, EPA or Food Safety and Inspection Service of the U.S. Department of Agriculture
Based on 45 CFR 46.101(b)
Is Exempt Research Subject to the Common Rule Requirements?
IRB review and approval is not required
Informed consent may be ethically required
Regulations do not specify who may make exemption determinations OHRP recommends determinations are made: ̶ By trained and qualified person (not necessarily the IRB) ̶ Not by investigator or members of the research team
Exemption category should be documented
Case Study #3
An investigator is conducting a survey among college students asking them to rate their professors. The students will be using SurveyMonkey to complete the data entry and their responses will be anonymous. The investigator is independent from the university faculty. What is the correct classification of this research? ̶ Not human subject research ̶ Exempt research, Category 2 ̶ Expedited review, Category 7
Case Study #3 Exempt research, Category 2
Step 1 – Is this research? ̶ Yes, researchers are collecting data on university professors.
Step 2 – Does it involved human subjects? ̶ Yes. The Investigator is interacting with college students via a survey.
Step 3 – Is it exempt? ̶ Yes. It is exempt under category 2. The students are not able to be identified by their survey responses.
Does Research Qualify for Exempt Review? – Step 3 If research does not qualify for exempt review proceed to step 4 – expedited review.
?
Levels of Review – Step 4 Full Board Step 5
Expedited? Step 4
Exempt? Step 3
Human Subject? Step 2
Research? Step 1
Does the Research Qualify for Expedited Review? – Step 4
No more than minimal risk
Definition: Minimal risk means that 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.
Does the Research Qualify for Expedited Review? – Step 4
Minor changes to previously approved research, during the period of approval
Must be done by IRB member(s)
Review criteria are the same as for full board review
Cannot disapprove by expedited review
IRB must be advised of expedited approvals
Expedited Review Categories – Step 4 Category #1
Research on drugs for which an IND application is not required
OR
Research on medical devices for which an IDE is not required
OR
The device is cleared/approved for marketing and is used in accordance with its label ̶
For research on medical devices for which an IDE is not required, needs to be ONE of the following:
⋄ Not a safety or effectiveness study ⋄ Exempt under 21 CFR 812.2(c)
Expedited review category 1
Expedited Review Categories – Step 4 Category #2
Blood collection from healthy, non-pregnant adults who weigh at least 110 pounds ̶ May not exceed 550 ml in 8 weeks and no more than 2 draws per week
From other adults and children ̶ May not exceed the lesser of 50 ml or 3 ml/kg in 8 weeks and no more than 2 draws per week
Expedited review category 2
Expedited Review Categories – Step 4 Category #3
Prospective collection of biological specimens for research purposes by noninvasive means ̶ Hair and nail clippings in a non-disfiguring manner ̶ Urine or sweat samples ̶ Placenta removed at delivery ̶ Mucosal and skin cells collected by swab
Expedited review category 3
Expedited Review Categories – Step 4 Category #4
Collection of data through noninvasive procedures (not involving anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves ̶ Weighing or testing sensory acuity ̶ Magnetic resonance imaging (no sedation or contrast)
̶ Physical examination ̶ Some types of blood or specimen testing (non-sensitive in nature)
Expedited review category 4
Expedited Review Categories – Step 4 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)
Expedited review category 5
Expedited Review Categories – Step 4 Category #6
Collection of data from voice, video, digital, or image recordings made for research purposes
Expedited review category 6
Expedited Review Categories – Step 4 Category #7
Research on individual or group characteristics or behavior or research employing survey, interview, oral history, focus group, or program evaluation
Expedited review category 7
Expedited Review Categories – Step 4
Category #8 and #9 involve continuing review
Expedited review categories 8 and 9
Case Study #4
A PI who is a scientist wants to prospectively obtain leftover urine samples (N=200) routinely collected in a pediatric clinic. The scientist in receipt of the samples will be working with the site and investigator who provided the samples to determine the incidence of unauthorized administration of antibiotics by parents. While the samples provided by the clinic will not have any identifiers, the clinic PI will also be involved in the research. What is the correct classification of this research?
̶
̶
̶
̶
Not human subject research Exempt research, Category 4 Expedited review, Category 3 and/or Category 5 Full Board review
Case Study #4 Expedited review, Category 3 and/or Category 5
Step 1 – Is this research? ̶ Yes, generalizable knowledge.
Step 2 – Does it involve human subjects? ̶ Yes, the PI who obtained the samples is also involved in the research and the samples are identifiable to him.
Step 3 – Is it exempt? ̶ No, exempt samples must be existing not prospectively collected.
Step 4 – Does it qualify for expedited review? ̶ Yes, Category 3 and/or Category 5.
Case Study #5
A PI wants to obtain 10 existing samples of pancreatic cancer tumors from the biorepository. The samples will have linked codes, but the PI will not have access to the link enabling him to identify the donors.
What is the correct classification of this research? ̶ Not human subject research ̶ Exempt research, Category 4
̶ Expedited review, Category 3 and/or Category 5 ̶ Full Board review
Case Study #5 Not human subject research
Step 1 – Is this research? ̶ Yes.
Step 2 – Does it involve human subjects? ̶ No, samples are not identifiable.
Activities do not meet the definition of human subject research and need not be reviewed by the IRB. ̶ The IRB can help investigators make this determination.
NPRM Changes
Notice of Proposed Rulemakings (NPRM’s) Changes
Definition of human subject ̶ Expanded to include all biospecimens- regardless of level of identifiability
̶ Non-identifiable human biospecimens will be considered human subjects and will be afforded regulatory protection ̶ NPRM proposes requiring informed consent for the storage and secondary research use of biospecimens. ⋄ This is called “broad consent.”
NPRM – Exclusions
Exclusions – activities that do not fall under the regulations ̶ PI makes decision
̶ IRB review not required but institution still held accountable ̶ 3 categories with a total of 11 exclusions ⋄ Category 1 - Excluded because activities are deemed “not research” (6 exclusions) ⋄ Category 2 - Low risk human subject research when already subject to independent controls (4 exclusions) ⋄ Category 3 - Low risk human subject research that does not meaningfully diminish subject autonomy (1 exclusion)
Conclusion
Always follow the steps, beginning at step 1 Determination is not always black or white ̶ The more information you can provide on your project, the better ̶ Plans for privacy, confidentiality and dissemination of findings
If in doubt, check with the IRB Refer to OHRP decision trees
References
OHRP Human Subject Regulations Decision Charts September 24, 2004 This does not include the FDA Regulations OHRP Quality Improvement Activities Frequently Asked Questions OHRP Guidance on Research Using Coded Private Information or Specimens OHRP Exempt Research Determination Frequently Asked Questions (FAQs)
Exempt & Non-Human Subjects Research Determination Request
Thank You!
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April 27, 2016
Determining the Review Level: Non-Human Subject Research, Exempt or Expedited Andrea Bidwell, MSN, RN, CIP IRB Member, Schulman IRB
