SOP 020: Flex Submission and Review

1. Purpose

The purpose of this SOP is to outline a flexible “Flex” IRB review process for minimal risk research that is not subject to federal regulations governing human subjects research and is not conducted or supported by any US federal agency. The flexible review process reduces administrative and regulatory burdens for minimal risk research that is not under federal purview while maintaining core ethical principles that protect the rights and welfare of research participants. For minimal risk research that is not conducted or supported by a US federal agency, WVU has the flexibility to apply IRB review standards that differ from federal regulations, provided research participants are afforded equivalent protections.

Please Note: WVU OHRP cautions that although research that is not federally funded is not required to meet federal regulations, the research is not exempt from the ethical guidelines of the Belmont Report and thus requires review and approval by WVU OHRP and the IRB.

2. Overview

The WVU OHRP provides a flexible IRB review option for minimal risk research projects that meet the required criteria specified below. While this policy allows for greater flexibility in the review process, it ensures equivalent protections for research participants. All research reviewed at WVU, regardless of research type, will be guided by the core ethical principles of respect for persons, beneficence, and justice. Equivalent protections include IRB review, human subject protection training, financial disclosures from research teams, agreement by participants for research involving direct interactions, provisions for confidentiality and security if data are identifiable, HIPAA protections when applicable, and the reporting of unanticipated problems.

The IRB Chair may designate an IRB member(s) or qualified WVU OHRP Administrator to review Flex protocol submissions. Reviewers are selected based on their expertise in the application content and knowledge of applicable regulations. If a designated reviewer is not available, the IRB Chair will review the submission.

Flex protocol submission numbers and outcomes are communicated to the IRB at the next convened meeting after approval of the project.

3. Procedures

3.1. Pre-Submissions

3.1.1. The PI should determine if the research project qualifies for Flex submission by reviewing Section 4 (Scope of this Policy) of this SOP.

3.1.2. The PI should complete the required training.

• The abbreviated CITI Program Biomedical Research Investigator or Social and Behavioral Research Investigator course satisfies the training requirements for Flex.
• WVU OHRP requires the full Biomedical or Social and Behavioral Research Investigator training course. If the protocol application is disqualified for Flex during the review, there could be delays in approval if the required training is not completed.

3.1.3. The PI should determine the regulatory requirements for the project and the data that will be collected or used during the project,complete the required forms and review the applicable guidance on the WVU OHRP website(e.g., HIPAA Waivers (if applicable), Data Protection Form, and Informational Cover letter and permission question with standard approved language.).

3.1.4. The PI should review the required provisions for vulnerable or disadvantaged populations, as directed in Section 5 (Vulnerable Populations).

3.1.5. The PI should create the Informational cover letter using the Flex template/guidance.

3.2. Pre-Submission

3.2.1. The PI should submit the completed Flex protocol application using the WVU electronic protocol submission system, and attach the following documents as applicable:

• Recruitment materials
• Informational Cover Letter
• Surveys, questionnaires, and data collection instruments – including the standard question to obtain voluntary permission to participate.
• Letter(s) of permission from each non-WVU site
• Research Data Protection Certification

3.3. WVU IRB Review

WVU OHRP staff are authorized by the IO and WVU OHRP Director to complete a preliminary review of the submitted protocol materials to determine completeness and accuracy. WVU OHRP staff assign protocols to IRB members (primary reviewers) for review paying close attention to the protocol’s scientific discipline, the potential reviewer’s area of expertise, and representation for vulnerable populations involved in the research.

A WVU IRB Chair (or designee) reviews all requests for research submitted under the Flex submission type and determines whether the application meets the criteria for inclusion.

3.4. WVU IRB Determinations

3.4. The reviewer may require additional protections for participants or require that the application be submitted or reviewed using an alternative submission type. Determinations made by the reviewer will be communicated with the Principal Investigator via the WVU electronic protocol submission system.

3.5. WVU IRB Approval

3.5. The approval of the Flex protocol application serves as formal documentation of the reviewer’s determination. Approved Flex protocols are granted a five (5) year approval period.

3.6. New protocol submissions are required for the following situations regarding Flex project changes:

• Amendments are not allowable for Flex protocols.
• Changes to current Flex projects that increase risk to participants require the Flex protocol to be submitted for review and approval as a new project before implementing the change.
• Changes in scope of the project (e.g., new or changed goals/hypothesis) or alterations in research procedures that significantly change the scope of the project (e.g., retrospective review adding a prospective component, adding a vulnerable population, etc.) require the Flex protocol to be submitted for review and approval as a new project before implementing the change.  
  
• Any federal funding awarded or funding from WVU CTSI require the Flex protocol to be submitted for review and approval as a new project before implementing the change.

Additional Human Subjects Protection (HSP) training may be required. Please refer to the WVU OHRP website for guidance on additional training.

3.7. Continuing Review

Approved Flex protocols are granted a five (5) year approval period. To extend the approval period beyond the initial five (5) year period, a new initial protocol application must be submitted for review and approval by the WVU IRB.

3.8. Reporting Requirements

Approved protocol applications must follow the reporting requirements outlined in SOP 031: Research Related Event Reporting.

4. Scope

4.1. The Flex submission type applies to:

• Research that is NOT federally funded or supported
• Federally funded or supported is defined at WVU as any of the following:
• Funded by a direct grant
• Funded through a sub-award or pilot grant associated with federal funds
• Includes personnel on a federally funded training grant
• Research conducted under a no-cost extension
• Data will be used to support an application for FDA approval or a grant application (e.g., data collection in response to a scored grant submission with plants to re-submit)
• Involves an FDA-regulated product or dietary supplement
• Involves data collection about FDA-regulated products
• Conducted under a contract that requires the investigator to adhere to federal human subjects regulations
  (e.g., 45 CFR 46, 34 CFR 97 or other references to the HHS Common Rule
• Involves any services that could be billed to a federal program
• Research that is Only Minimal Risk (OMR)
• 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.

4.2. Excluded

4.2.1. Research that cannot be submitted using the Flex submission type

Expedited Category Four (4)

1. Research with federal funding - Per 45 CFR 46.101(a), research that receives federal funding is regulated by the Common Rule.
2. Research supported, in full or in part by programs that are supported by federal funding: WV Clinical & Translational Science Institute (CTSI), WV IDeA Network of Biomedical Research Excellence (WV-INBRE), Center of Biomedical Research Excellence (CoBRE), or other programs supported by federal funding.
3. Research involving the Food and Drug Administration (FDA) regulated elements.
1. Research approvable under Expedited Category 1 (45 CFR 46.110)
   including:

• Research related to drugs for which an Investigational New Drug application is not required.
• Research on medical devices for which an Investigational Device Exemption is not required or the medical device is approved for marketing and used following its approved label.
• Research requiring an Investigational New Drug (IND) or Investigational Device (IDE) Exemption application(s).

Sensitive topics in research:

• Research related to alcohol and drug treatment
• Research related to suicide or suicide ideation
• Research related to sexual behavior or practices
• Research related to illegal activities or ethically questionable behaviors
• Research related to racism, ageism, classism, discrimination, and sexism
• Research involving experiences of grief and loss, trauma, or violence
• Research related to job performance of competency
• Research involving other stigmatizing or controversial topics, as determined by WVU OHRP/IRB 
  

Certificate of Confidentiality awarded by the NIH:

• Applying for or obtaining an NIH Certificate of Confidentiality implies a risk to participants should their identity be disclosed outside of the research. 

Prisoner Populations

• Research targeting prisoner populations. Persons in transitional custody whose liberty is restricted, such as halfway houses, electronic monitoring, probation, or house arrest, are not considered by WVU human research protections program to meet the federal definition of a prisoner. For those individuals, the criteria at 45 CFR 46.111 offers sufficient protection for their level of vulnerability.

Flex - Other Protected Populations

• Research targeting tribal members, military personnel, wards of the state, or cognitively impaired individuals are not permitted under the Flex Model. 

International research

Research involving genetic testing

Flex collaborative research

Research requiring an IRB Authorization Agreement (IAA)

Some research involving minors

Clinical trials

4.3. Included

4.3.1. Research that can be submitted using the Flex submission type

• Collection of biological specimens for research purposes by noninvasive means, such as hair and nail clippings, saliva, urine, or cheek swabs.
• Research involving tissues and samples collected under Standard of Care procedures:
• Collection of blood samples from healthy, non-pregnant adults who weigh at least 110 pounds may not exceed 550ml in 8 weeks, and collection may not occur more frequently than twice per week.
• Collection of blood samples from other adults and children may not exceed the lesser of 50ml or 3ml/kg
  in 8 weeks and collection may not occur more frequently than twice per week.
• Tissue or sample extraction or collection would be conducted regardless of the research (as the Standard of Care). Only identifiable samples collected for this Standard of Care procedure are permitted to be used. An example of this would be a Standard of Care tooth extraction. If an additional sample or volume is needed in addition to the Standard of Care, the research cannot be submitted using Flex.
• Review of data that have been collected, or will be collected, solely for non-research purposes. 
• Research permitted and approved under Expedited Categories 2 and 3 (45 CFR 46.110).
• Research permitted under Exempt Category 4 (45 CFR 46.101(b)(4) or Expedited Category 5 (45 CFR 46.110).
• The recording/collection of Personally Identifiable Information (PII) and Protected Health Information (PHI). 
• Application for Waiver of HIPAA requirements must be attached with the Flex application and, if appropriate, approved by the IRB Chair or designee.
• Retrospective or Prospective research
• Prospective research - the participant should be consented or meet the conditions to waive informed consent, as applicable.
• Deception
• Deception is research in which participants are intentionally deceived as to the purpose of the research must have an adequate de-briefing and opt- out plan.
• Research involving minimal risk intervention (Expedited Categories 6 & 7)
• Participants are asked to complete minimal risk behavioral interventions that are brief, harmless, painless, and not physically and/or emotionally invasive or offensive (i.e., asking subjects to play an online game or solve puzzles under varying noise conditions). The information obtained and recorded should not risk damaging the subject criminally, financially, their employability, educational advancement, or reputation.

5. Vulnerable Populations

5.1. Flex submissions related to research involving protected populations including, but not limited to the list below must include sensitivity considerations and provisions:

Protected Populations and Requirements

Pregnancy

Pregnant adult women may be included. However, the research should not expose the fetus or mother to more than minimal risk.

Consent must be sought and obtained from the participant, using an Informational Cover letter and (when applicable) permission question with standard approved language.

Children

Participants under the age of 18 years old may be included. The research should not involve more than minimal risk, and tasks should be limited to benign interventions.

Unless waived, parental consent and child assent must be sought and obtained, using the Informational Cover Letter (when applicable) permission question with standard approved language.

6. Informed Consent

6.1. A Waiver of Documentation of Informed Consent will automatically be applied to all qualified Flex Applications; however, reviewers retain the right to require signatures from participants and the PI conducting the consent process.

6.2. PIs should customize the Informational Cover letter and (when applicable) permission question with standard approved language for the research project. The form should be presented to the participant, either physically or via electronic communications (i.e., online survey) before the participant begins research-related activities. Participants should indicate their willingness to participate in the study after reading the cover letter.

6.3. Parental Permission is required for approved research that targets children under 18 years of age.

7. References

WVU Policies:
SOP 007: IRB Approval Criteria
SOP 008: IRB Determinations
SOP 031: Research Reporting Requirements
SOP 036: Research Data Use and Protection

Federal Regulations:
21 CFR 56.104 (c) and (d)
45 CFR 46.101, 301, 401

AAHRPP:
Standard II.2