Investigator Manual

Activities must meet the institutional definition of “Human Research” to fall under IRB oversight. Activities that do not meet this definition are not subject to IRB oversight or review. Submissions in WRAP are not required.

See What is Human Research? for additional information. Review HRP–310—Worksheet—Human Research Determination (DOCX) and HRP–503b—Template—NHSR Protocol (DOCX) for reference. Use HRP-207—Form—QA/QI and Program Evaluation Self-Certification Tool (Kuali Build) , if applicable.

For submission in WRAP

• Use HRP–503b—Template—NHSR Protocol (DOCX) or HRP–503c—Template—Secondary Research Protocol (DOCX).
• Submit Letter of Support for relevant unit, class, school, agency, etc.
• If available, provide documentation that a formal determination is required (by funding agency, publication, etc.).

• Exempt

  Certain categories of Human Research may be exempt from regulation but require IRB review. It is the institution—not the investigator— that determines exemption status.

  Review HRP-312—Worksheet—Exemption Determination (DOCX) for reference.

  • Use HRP-503e—Template—Exemption Determination Protocol (DOCX) or HRP-503c—Template—Secondary Research Protocol (DOCX), as applicable in WRAP.

• Review Using the Expedited Procedure

  Certain non-exempt categories may qualify for review using the expedited procedure, meaning approval may be granted by a single designated IRB reviewer rather than the convened board.

  Review HRP-313—Worksheet—Expedited Review (DOCX) for reference.

Non-exempt Human Research that does not qualify for expedited review must be reviewed by the convened IRB.

• Use HRP-503—Template Protocol (DOCX), HRP-503a—Template SBS Protocol (DOCX), or HRP-503d—Template Humanitarian Use Device Protocol (DOCX).

Please thoroughly review criteria below before submitting. Many single patient IND or compassionate use submissions are non-emergency.

See How do I submit a non-emergency expanded access request for an unapproved drug, biologic, or device to the IRB? for more information.

Criteria for emergency use

According to FDA regulations, the emergency use exemption may be used if all of the following conditions are met:

1. A test article is any drug, biologic, or medical device for human use; human food additive; color additive; electronic product; or any other article subject to FDA regulations.
2. The individual for whom the test article is intended is in a life-threatening situation.
1. To meet the life-threatening criterion, the condition does not have to be immediately life-threatening or immediately result in death.
2. Life-threatening also includes "severely debilitating."
3. "Severely debilitating" does not include pre-existing (e.g., chronic) diseases or conditions with major morbidity.
3. No standard acceptable treatment is available.
1. Also, the individual for whom the test article is intended does not meet the enrollment criteria for an existing IRB-approved study or an approved study does not exist 
4. There is not sufficient time to obtain IRB approval.
1. Typically, this means same day or over the weekend use. WVU IRB can typically provide IRB Chair concurrence for a non-emergency single patient IND in WRAP in a timely manner, often same day. 

If you have questions about whether the situation is emergency use or a non-emergency single patient IND, please email irb@mail.wvu.edu.

IRB Chair Concurrence for Emergency Use is obtained through a HRP-208—Form—WVU Emergency Use Concurrence Request.

If there is no time request IRB chair concurrence prior to using the test article, see HRP-322—Worksheet—Emergency Use (DOCX) for the regulatory criteria allowing such a use and make sure these are followed. Use HRP-506—Template—Consent Document-Emergency or Compassionate Devise Use (DOCX) to prepare your consent document.

Include in the report a description of how the use meets the criteria outlined in HRP-322—Worksheet—Emergency Use (DOCX), a summary of the patient’s diagnosis and treatment history, and date and time of the use. Attach to the report the consent document templates used (if applicable), approval of the use from the FDA (drugs and biologics), or concurrence letter from an independent physician that the use of the device is warranted and no other alternative treatments are/were available (devices).

Individuals getting an unapproved drug, biologic, or device without prior IRB review cannot be considered a “subject” as defined by DHHS and their results cannot be included in prospective “research” as that term is defined by DHHS.

FDA regulations require that any subsequent use of a test article at the institution have prospective IRB review and approval. If it is anticipated that this test article may be used again (for the same patient, a different patient, or for any indication), submit a protocol and consent document(s) to the IRB for review so that an approved protocol will be in place when the next need arises.

The emergency use of an investigational drug or biologic requires an IND. To obtain an emergency use IND, a physician/researcher should contact the product manufacturer or sponsor to determine if the investigational drug or biologic can be made available for the emergency use under the company’s IND. Alternatively, if the manufacturer/sponsor will not provide the investigational product under its IND, a physician/researcher may contact FDA directly to obtain authorization for the company to ship the drug or biologic for the specific emergency situation in advance of an IND submission. For more information, please see FDA Contacts for Obtaining an Emergency IND. Some manufacturers or sponsors will agree to the emergency use of an investigational drug or biologic, but require an “IRB approval letter” before shipping the product.

FDA approval prior to emergency use or shipment of an unapproved medical device is not required. The emergency use may involve a device that does not have an existing IDE, a device used in a way that is not approved under an existing IDE, or a physician who is not named as an investigator to the IDE. Whenever possible, authorization should be obtained from the sponsor (if an IDE exists for the device) before the emergency use. In addition to determining that the criteria for emergency use are met, physicians/researchers are required by FDA to assess the potential for benefit from the use of an unapproved device and to have “substantial reason” to believe that benefits will occur. Whenever possible, an independent assessment of the circumstances prior to emergency use should also be obtained from a physician who is not otherwise involved in the emergency use. If the device has an existing IDE and the physician/researcher could not obtain authorization from the sponsor prior to the emergency use, the physician/researcher is responsible for reporting to the sponsor within five working days. The emergency use of an unapproved device must be reported to FDA by the sponsor (if an IDE exists for the device) within five working days of the time the sponsor learns of the use. If no IDE exists, the physician/researcher is responsible for reporting the emergency use directly to FDA.

Non-emergency expanded access requests are submitted in WRAP as a new study. Please put “single patient IND,” “compassionate use,” or “expanded access” in the title, as applicable, when submitting.

Complete the New Study SmartForm in WRAP and attach all requested supplements, have the SmartForm submitted by the PI by clicking the “Submit” activity. Maintain electronic copies of all information submitted to the IRB in case revisions are required.

There are five different types of non-emergency use expanded access:

1. Individual patient expanded access use of an investigational drug
   Individual patient drug expanded access requests should be submitted to the IRB as a new study. If the study team checked “Request for Authorization to Use Alternative IRB Review Procedures” on FDA Form 3926 (field 10.b.) or has a separate waiver request included with FDA Form 1571 for the purpose of obtaining concurrence from an IRB Chair or designee, this information should be included in the application. Instead of uploading a protocol, the submission should include the following:
   • A thorough patient history and treatment plan, included in Form FDA 3926 or in a separate document, that includes:
     • The proposed daily dose, route, and frequency of administration; duration of planned treatment; criteria for discontinuation; and planned dose modifications for adverse events.
     • The planned monitoring for adverse events, response to treatment, and changes in clinical status, as well as proposed modifications to the treatment plan to mitigate risks if appropriate.
     • Key details of the patient’s history, including diagnosis and summary of prior therapy (including response); the reason for request and why the patient lacks other therapeutic options; and relevant clinical characteristics (e.g., comorbid conditions, concomitant medications) needed to assess potential increased risks of the drug.
     • A summary of known risks of the drug.

   Use HRP-506––Template Consent Document-Expanded Access (DOCX) to prepare your consent document. A Continuing Review application must be submitted to the IRB at least annually, and any modifications or new information should be reported accordingly.

2. Compassionate Use (Individual patient/small group access) of a device

   Requests for compassionate use of a device should be submitted to the IRB as a new study. See HRP-325––Worksheet––Device Compassionate Use (DOCX) for the regulatory criteria allowing such a use and make sure these are followed. The FDA does not consider the compassionate use of an unapproved device to be a clinical investigation, however it is expected that informed consent be obtained. Use  HRP-506––Template Consent Document-Expanded Access (DOCX) to prepare your consent document.

   Instead of uploading a protocol, the submission should include a summary of the conditions constituting the compassionate use, other relevant details of the case, approval from the device manufacturer, device/product manual, FDA authorization, and any other relevant information (i.e., patient-facing materials, etc.). Continuing review is not required for compassionate use, however if any problems occurred as a result of device use, these should be discussed in the follow-up report and reported to the IRB as soon as possible.

3. Intermediate-size patient population access of a drug
4. Expanded access for widespread use of a drug
5. Treatment use of a device

Requests for any of these three (3) types of expanded access use should be submitted to the IRB as a new study. Submissions should include the protocol, consent form, and other pertinent information (i.e., Investigator’s Brochure, device/product manual, patient-facing materials, etc..). Use HRP-502––Template Consent Document (DOCX) to prepare your consent document. A Continuing Review application must be submitted to the IRB at least annually, and any modifications or new information should be reported accordingly.

This Institution utilizes the IRB to review and approve the use of a HUD before it can be used at a facility for clinical care. You can refer to HRP-323––Worksheet––Criteria (DOCX) for Approval HUD for additional information regarding the criteria that the IRB uses to review and approve HUD uses. The clinical use of a HUD is not considered Human Research but must still be submitted for review and approval by the IRB prior to clinical use (with the exception of emergency use). An informed consent form is not required by the IRB for HUD use.

Complete the New Study SmartForm in the WRAP. Select “Yes” to “Does the study evaluate the safety or effectiveness of a device or use a humanitarian use device (HUD)?” under Study Scope and complete the Device SMARTForm with the information about the HUD, including the HDE number. Attach all requested supplements, including a completed HRP-503d––Template––Humanitarian Use Device Protocol (DOC) document, and have the SmartForm submitted by the PI by clicking the “Submit” activity. Maintain electronic copies of all information submitted to the IRB in case revisions are required.

Certain types of applications for grants, cooperative agreements, or contracts are submitted to Federal departments or agencies with the knowledge that subjects may be involved within the period of support, but definite plans would not normally be set forth in the application or proposal. These include activities such as institutional-type grants where selection of activities is the institution’s responsibility, training grants in which activities involving human subjects remain to be selected, and projects where human subject involvement will depend on the design and development of study materials and instruments. Often the funding agency requests an approved in principle letter to release the funds.

This determination is designed to help facilitate review of research lacking definite plans for the involvement of human subject research in accordance with the regulations set forth in 45 CFR 46.118. For example, projects in which human subjects' involvement is planned for a later phase of the research but it is not possible to know the details for that phase because they will depend upon completion of instruments, prior animal studies, or purification of compounds. This is different from situations where the researchers haven’t completed their IRB materials, haven't hired/trained staff or haven't received all necessary permissions to do their research.

To request an approved-in-principle letter, email irb@mail.wvu.edu. Approved-in-principle letters are not appropriate for NIH Just-In-Time awards.

No human subjects research activities may occur with an approved in principle determination. Once human subjects research plans are definitive, an IRB protocol in WRAP must be submitted and approved prior to initiating those activities.

Yes. WVU OHRP provides protocol templates for use. Industry developed or other protocols can be attached. If using an industry developed or other protocol template, WVU OHRP recommends including HRP-508—Template–Site Supplement to assist with review and categorization of IRB submissions.

WVU OHRP/IRB has these templates available for use:

• HRP-503—Template—Protocol
• HRP-503a—Template—SBS Protocol
• HRP-503b—Template—NHSR Protocol–Reference Only
• HRP-503c—Template—Secondary Research Protocol
• HRP-503d—Template—Humanitarian Use Device
• HRP-503e—Template—Exemption Determination Protocol

See How do I know which protocol template to use? Opens related accordion pane for additional guidance.

Use HRP-503—Template—Protocol (DOCX) as a starting point for drafting a new Investigator Protocol and reference the instructions in italic text for the information the IRB looks for when reviewing research. Here are some key points to remember when developing an Investigator Protocol:

• The italicized bullet points in HRP-503—Template—Protocol  serve as guidance to investigators when developing an Investigator Protocol for submission to the IRB. All italicized comments are meant to be deleted prior to submission.
• For any items described in the sponsor’s protocol or other documents submitted with the application, investigators may simply reference the page numbers of these documents within the Investigator Protocol rather than repeat information.
• When writing an Investigator Protocol, always keep an electronic copy. You will need to modify this copy when making changes to the Investigator Protocol.
• If your activity is not Human Research, you are not required to submit in WRAP.
• Note that, depending on the nature of your research, certain sections of the template may not be applicable to your Investigator Protocol. Indicate this as appropriate.
• You may not involve any individuals who are members of the following populations as subjects in your research unless you indicate this in your inclusion criteria as the inclusion of subjects in these populations has regulatory implications.
  • Adults unable to provide legally effective consent
  • Individuals who are not yet adults (infants, children, teenagers)
  • Pregnant women
  • Prisoners
• If you are conducting community-based participatory research, you may contact WVU OHRP for information about:
  • Research studies using a community-based participatory research design
  • Use of community advisory boards
  • Use of participant advocates
  • Partnerships with community-based institutions or organizations

Review the table to select the correct protocol template documents.

Use one of the HRP-502 templates to create a consent document. WVU OHRP has theses consent templates for use:

Note that all long form consent documents and all summaries for short form consent documents must contain all of the required and all additional appropriate elements of informed consent disclosure. Review the “Long Form of Consent Documentation” section in HRP-314a—Worksheet—Criteria for Consent, to ensure that these elements are addressed. When using the short form of consent documentation, the appropriate signature block from HRP-502—Template—Adult Medical Consent should be used on the short form.

We recommend that you date the revisions of your consent documents to ensure that you use the most recent version approved by the IRB.

An electronic consent (eConsent) process must satisfy all the usual requirements for informed consent for research. 

OHRP

Participant must receive a signed copy of the consent document.

FDA

Participant must receive a signed copy of the consent document. The investigator is responsible for obtaining legally effective informed consent. Must be 21 CFR Part 11 compliant.  

HIPAA

Participant must receive a copy of the signed authorization. Must use a HIPAA-compliant system.  

GCP

Participant should receive a signed copy of the consent document with both his/her signature (or LARs) with the date and the signature with the date of the person who conducted the informed consent process.

Using eConsent

Study teams utilizing eConsent must thoroughly test the eConsent process, even when using the available templates. The study team should understand their role in the consent process as well as understand the experience of the participant. This will allow the study team to assist participants during the consent process and address any questions/concerns the participants may have.

The WVU OHRP/IRB expects principal investigators and study teams to understand the eConsent process and be able to execute their consent process independently.

As with any human subjects research project, the eConsent process is more than the document. Study teams must give careful consideration to how the consent will be presented, how participants’ understanding will be evaluated, how participants’ questions and concerns will be addressed, etc. For additional requirements, please review the shared FDA and OHRP guidance.  

Templates are available in REDCap for eConsent.

Qualtrics is not recommended for use unless using HRP-502e—Cover Letter Template (DOCX).  

If you are using HRP-502e—Cover Letter Template, you can copy and paste the language into the electronic platform (e.g., Qualtrics or REDCap).  

When submitting in WRAP, include a PDF or Word document of the cover letter/consent document as well as a PDF of the Qualtrics or REDCap project. 

Studies that pose greater than minimal risk to subjects must include a DSMP. A Data Safety Monitoring Board (DSMB) may also be required if the study involves blinding, multiple sites, vulnerable subjects, or employs high-risk interventions. The NIH requires the establishment of DSMBs for all Phase III multi-site clinical trials involving interventions that entail potential risk to the subjects.

WVU is a HIPAA Hybrid Entity. Per WVU Policy 1.11.3.6: The University is a single legal entity, comprised of multiple and distinguishable schools, departments, clinics, programs, and functions, some of which may conduct both covered functions and non-covered functions under HIPAA.

The University has determined that there are a number of its components that either do or do not use or disclose PHI; accordingly, to effectively and efficiently safeguard the use and disclosure of PHI and to focus its HIPAA compliance efforts on University Health Care Components, the University hereby elects to designate itself as a Hybrid Entity.

Exhibit A in the linked policy above outlines the departments, schools, clinics, programs, etc. in the covered entity.

A HIPAA Waiver of Authorization is needed when researchers at the covered entity are conducting prospective studies.

The following three criteria must be satisfied for a privacy board to approve a waiver of authorization under the Privacy Rule. At WVU, the WVU IRB serves as the HIPAA privacy board and will issue the HIPAA waiver as part of the IRB review process: 

1. The use or disclosure of protected health information (PHI) involves no more than minimal risk to privacy, based on all of the following:
   1. An adequate plan to protect identifiers from improper use and disclosure.
   2. An adequate plan to destroy identifiers at the earliest opportunity consistent with the research, unless justified to retain them or required by law.
   3. Adequate written assurances that PHI will not be reused or disclosed to others, except as required by law, for authorized oversight, or for other permitted research under this subpart.
2. The research could not practicably be conducted without the waiver.
3. The research could not practicably be conducted without access to and use of PHI.

1. identifying eligible potential participants for study through medical record review (Part of the project; recruitment; accessing the medical record prior to signed authorization) 
2. Secondary data analysis/research on a large set of medical records (entire project).

A waiver for part of a project, or an entire project, can also be appropriate in other situations.

Research activities that involve PHI should be conducted whenever practicable with patient authorization (i.e., use of combined consent and authorization). If researchers have the opportunity to interact with the participant, researchers are expected to obtain a signed consent and HIPAA authorization. As noted above, study teams must demonstrate that the research could not practicably be conducted without the waiver. This criterion is not met in situations where the study team will interact with the participant. Likewise, it may be feasible to obtain a signed authorization from each individual in a small data set.

Data custodians (e.g., WVCTSI) may be able to provide a study team with a de-identified or a coded dataset that fulfills the research needs. De-identified datasets do not require a HIPAA Waiver but coded datasets may, depending on whether the researcher has access to the linking code.

Investigators must provide detailed information regarding how subjects will be identified and recruited in the protocol. Recruitment methods and advertisements that will be used in human subjects research require prospective review and approval by the IRB.

The IRB does not allow “cold calls/approaches” to potential research subjects. "Cold calling" is the practice of investigators or research staff initiating contact with the potential subject for research based on prior knowledge of private information. Alternatives to cold calling include but are not limited to:

• Individuals that have previously agreed to be contacted for research purposes.
• A letter or email of introduction from a direct care provider or organization leader (i.e. someone who has an established relationship with the potential subject) is an acceptable method of disseminating information regarding research opportunities. This information should contain pertinent information regarding the proposed research and contact information of the study team. Typically, this letter is sent under the name of the individual with whom the potential subject has a direct relationship (i.e. the individual’s primary or specialty care provider or trusted individual).
• Listserv announcements to groups of potential subjects pertinent information regarding the proposed research and contact information of the study team. Ensure that you have authority to access the email list and that the individuals are blinded from other potential subjects email addresses.
• MyChart messages that use the MyChart template.

However, the IRB may not deem these methods of recruitment appropriate for certain research topics, or may approve other methods of recruitment involving calling, emailing, or sending letters depending on the study population.

Required Elements of Research Advertisements:

• Clearly state that the advertisement is for participation in a research project.
• State the purpose of the research.
• Summarize the eligibility criteria.
• Provide the benefits to the participant, if applicable.
• Indicate the time and participation commitment.
• Indicate the location of the research.
• Provide the name, address/email, and department of the Principal Investigator (PI).
• Provide a contact person and phone number.
• Indicate that WVU IRB approval is on file.
• Do not imply a certainty of a favorable outcome or other benefits beyond the information contained in the consent document and the protocol.
• Do not include exculpatory language.
• Do not emphasize compensation by using a larger, bold, or different color font.

Advertisements for Research Involving Drugs, Devices, or other Test Articles:

• Do not make claims either explicitly or implicitly that the drug, biologic, or device was safe or effective for the purposes under investigation.
• Do not make claims either explicitly or implicitly that the drug, biologic, or device was known to be equivalent or superior to any other drug, biologic, or device.
• Use terms such as "investigational new treatment," "investigational new medication," or "investigational new drug."
• Do not promise "free medical treatment" when the intent is to indicate that participants will not be charged for their participation in the research.
• If a placebo is used, clearly state that some participants may receive a placebo.

Please use the COE MyChart Template with examples under "WVCTSI Resources" on the WV Center of Excellence (COE) website in order to streamline the advertisement approval process.

In addition to applicable consent documents and a protocol, the following items should be included in your IRB submission:

• Any participant facing materials:
  • Advertisements (includes web and paper postings)
  • Recruitment materials (emails, web postings, etc.)
  • Any data collection tools
  • Questionnaires
  • Surveys
  • Interview questions
  • Variable lists
• Other study documents
• Investigator’s Drug Brochure
• Device specifications/information
• Any additional regulatory documents

Complete the New Study SmartForm in WRAP and attach all requested supplements, have the SmartForm submitted by the PI (or PI proxy) by clicking the “Submit” activity. Maintain electronic copies of all information submitted to the IRB in case revisions are required.

Yes, in addition to IRB review and approval, your study may require review by other units/entities at the university. Many of these reviews can be started before you submit your IRB application. See HRP 309–Worksheet—Ancillary Review Matrix (DOCX) for more information about institutional requirements.

HRP 309–Worksheet—Ancillary Review Matrix is NOT a comprehensive list of institutional requirements. PIs are responsible for ensuring their research is conducted in compliance with all applicable university and health system policies. IRB approval does not represent institutional permission to conduct the research but instead one of many required approvals to conduct human subjects research at the institution.

You will see the option to “Withdraw” after you have submitted to WVU OHRP/IRB and before the protocol is approved. You can “Withdraw” your submission to move it back to the Pre-Submission state.

You will also see the option to “Discard” your submission. This will permanently delete the submission.

After the PI or the PI proxy submits to the IRB in WRAP, the submission is assigned to an IRB coordinator. The IRB coordinator reviews the submission for completeness. If there are any missing materials or outstanding questions, the IRB coordinator uses the Request Clarifications function.

The study team addresses any requested revisions, uploads any missing materials, and returns the submission to WVU OHRP.

Once the requested clarifications have been addressed and the submission is returned to the WVU OHRP, the IRB coordinator assigns the submission to a designated reviewer, if the study is undergoing non-committee review. If the study requires review by the convened board, the study will be assigned to the next available committee meeting.

The IRB may approve research, require modifications to the research to secure approval, table research, defer research or disapprove research:

Approval

Made when all criteria for approval are met. See How does the IRB decide whether to approve Human Research? .

Modifications Required to Secure Approval

Made when IRB members require specific modifications to the research before approval can be finalized.

Tabled

Made when the IRB cannot approve the research at a meeting for reasons unrelated to the research, such as loss of quorum. When taking this action, the IRB automatically schedules the research for review at the next meeting.

Deferred

Made when the IRB determines that the board is unable to approve research and the IRB suggests modifications that might make the research approvable. When making this motion, the IRB describes its reasons for this decision, describes modifications that might make the research approvable, and gives the investigator an opportunity to respond to the IRB in person or in writing.

Disapproval

Made when the IRB determines that it is unable to approve research and the IRB cannot describe modifications that might make the research approvable. When making this motion, the IRB describes its reasons for this decision and gives the investigator an opportunity to respond to the IRB in person or in writing.

The criteria for IRB approval can be found in HRP-312-Worksheet—Exemption Determination (DOCX) for exempt Human Research and HRP-314—Worksheet––Criteria for Approval for non-exempt Human Research (DOCX) . The latter worksheet references other checklists that might be relevant. All checklists and worksheets can be found in the HRPP Toolkit.

These checklists are used for initial review, continuing review, and review of modifications to previously approved Human Research.

You are encouraged to use the checklists to write your Investigator Protocol in a way that addresses the criteria for approval. You may also consider uploading completed checklists for reference under Other Attachments in your IRB submission.

The IRB will provide you with a written decision indicating that the IRB has approved the Human Research, requires modifications to secure approval, or has disapproved the Human Research.

If the IRB has approved the Human Research

The Human Research may commence once all other institutional approvals have been met. IRB approval is usually good for a limited period of time which is noted in the approval letter. Some projects do not have an expiration date. All research studies should be closed in WRAP when the completed.

If the IRB requires modifications to secure approval and you accept the modifications

Make the requested modifications and submit them to the IRB. If all requested modifications are made, the IRB will issue a final approval. Research cannot commence until this final approval is received. If you do not accept the modifications, write up your response and submit it to the IRB.

If any documents are updated in response, study teams use the “Update” option next to the document name to replace the document. Study teams can upload tracked changes versions of documents. This ensures appropriate document control and version history. Do not use the delete option.

If the IRB defers the Human Research

The IRB will provide a statement of the reasons for deferral and suggestions to make the study approvable and give you an opportunity to respond in writing. In most cases if the IRB’s reasons for the deferral are addressed in a modification, the Human Research can be approved

If any documents are updated in response, study teams use the “Update” option next to the document name to replace the document. Study teams can upload tracked changes versions of documents. This ensures appropriate document control and version history. Do not use the delete option.

If the IRB disapproves the Human Research

The IRB will provide a statement of the reasons for disapproval and give you an opportunity to respond in writing.

Most IRB protocols have undergone scientific review prior to submission.

The IRB review process also always includes a scientific review. The IRB reviewer may use HRP–320—Worksheet—Scienfic or Scholarly Review (DOCX) when reviewing an assigned protocol. For any study, the WVU IRB may require a scientific review be conducted by an appropriate individual or individuals. This may include an outside consultant, department chair, or other appropriate individual, as determined by the IRB. In this circumstance, an ancillary review is assigned or HRP–051—SOP—Consultation (DOCX) is followed.

1. Do not start Human Research activities until you have the final IRB approval letter.
2. Do not start Human Research activities until you have obtained all other required institutional approvals, including approvals of departments or divisions that require approval prior to commencing research that involves their resources.
3. Ensure that there are adequate resources to carry out the research safely. This includes, but is not limited to, sufficient investigator time, appropriately qualified research team members, equipment, and space.
4. Ensure that Research Staff are qualified (e.g., including but not limited to appropriate training, education, expertise, credentials, protocol requirements and, when relevant, privileges) to perform procedures and duties assigned to them during the study.
5. Update the IRB office with any changes to the list of study personnel.
6. Personally conduct or supervise the Human Research. Recognize that the investigator is accountable for the failures of any study team member.
   1. Conduct the Human Research in accordance with the relevant current protocol as approved by the IRB, and in accordance with applicable federal regulations and local laws.
   2. When required by the IRB ensure that consent or permission is obtained in accordance with the relevant current protocol as approved by the IRB.
   3. Do not modify the Human Research without prior IRB review and approval unless necessary to eliminate apparent immediate hazards to subjects.
   4. Protect the rights, safety, and welfare of subjects involved in the research.
7. Submit to the IRB:
   1. Proposed modifications as described in this manual. (See How do I submit a modification? )
      1. Single subject protocol exceptions should be submitted via the modification process.
   2. A continuing review application as requested in the approval letter. (See How do I submit continuing review? )
   3. A continuing review application when the Human Research is closed. (See How Do I Close Out a Study? )
8. Complete the Report New Information SmartForm within 5 business days of becoming aware of any items outlines in “What am I required to report to the IRB?
9. Submit an updated disclosure of financial interests within thirty days of discovering or acquiring (e.g., through purchase, marriage, or inheritance) a new financial interest.
10. Do not accept or provide payments to professionals in exchange for referrals of potential subjects (“finder’s fees.”)
11. Do not accept payments designed to accelerate recruitment that were tied to the rate or timing of enrollment (“bonus payments.”)
12. See additional requirements of various federal agencies in Appendix A. These represent additional requirements and do no override the baseline requirements of this section.
13. If the study is a clinical trial and supported by a Common Rule agency, one IRB-approved version of a consent form that has been used to enroll participants must be posted on a public federal website designated for posting such consent forms. The form must be posted after recruitment closes, and no later than 60 days after the last study visit. Please contact the study sponsor with any questions.
1. If certain information should not be made publicly available on a Federal website (e.g. confidential commercial information), the supporting Federal department or agency may permit or require redactions to the information posted. Contact the Federal department or agency supporting the clinical trial for a formal determination.
2. Contact the supporting Federal department or agency sponsor with any other questions regarding consent form posting obligations.

Studies approved as expedited or full board must submit modifications for IRB review and approval before initiating any change. See your approval letter to determine your study review type.

WVU OHRP requires the following modifications be submitted for exempt studies:

1. Change in PI
2. Changes that may affect the exemption determination
3. Changes in study staff to allow COI to complete their required reviews and to meet HIPAA compliance/covered entity policies and procedures
4. Addition of or changes to WVU MyChart message in compliance with WVCTSI SOPs

WVU OHRP requires the following modifications to be submitted for studies with an external IRB of record:

1. Changes in personnel or principal investigator.
2. Changes to a conflict of interest management plan.
3. Changes to HIPAA authorization waivers or alterations

Complete the Modification SmartForm in WRAP and attach all requested supplements, have the SmartForm submitted by the PI by clicking the “Submit” activity. Maintain electronic copies of all information submitted to the IRB in case revisions are required. When replacing documents in WRAP, you must select the “Update” option for the document. DO NOT select delete and then re-upload the updated document. For document control to work appropriately in WRAP, you must use the “Update” option.

Please note that research must continue to be conducted without inclusion of the modification until IRB approval is received.

Note that there are two types of modifications (scope) that can be submitted: “Updates to study team member information” and “Other parts of the study.” There can only be one of each type of modification in process at any given time (i.e., you can only have one study team member modification reviewed at a time), but you may have modifications of both types being processed at any given time (i.e., you can have a study member update and other parts of the study modification in process at the same time).

Changes of PI often prompt changes to other parts of the study. Review all consent/assent forms, recruitment materials and other documents to make certain they have been updated to reflect the change. The current PI may transfer responsibility to a new PI by submitting a modification (See How do I submit a modification? ).Once an investigator leaves the institution, they are no longer covered by the WVU IRB unless a reliance agreement is in place.

If the current PI is leaving WVU but will continue working on the study at a new institution, review the requirements for:

Human Subjects Research Going to Another Institution from WVU (PI leaves WVU and the study IS NOT under the Single IRB Mandate)

• The departing PI, after consulting with WVU OHRP staff and their new institution’s IRB, submits a Modification Request in WRAP to change the PI on the study from that of the departing PI to an authorized WVU employee who can serve as the new WVU PI. This ensures the continuity of the research until the departing PI obtains IRB approval, if applicable, at their new institution.
• The departing PI is completely removed from the protocol in WVU’s electronic IRB submission system.
• If the research is not continuing at WVU, the new PI of the WVU protocol closes the protocol within six (6) months of the departing PI’s separation from WVU. Protocols not closed by the new PI within six (6) months may be closed administratively by WVU OHRP and/or the IRB.
• If the research is continuing at WVU, no additional action is required, and the research continues under the new PI and operates under WVU OHRP SOPs. If the departing PI and new institution are involved in the research, the new institution is responsible for the oversight of the research activities at their site.

Research Going to Another Institution (PI separates from WVU and the study IS under the Single IRB Mandate)

See section Single IRB Reliance . The departing PI and new WVU PI will follow this process for moving their research new institution and continuing the research at WVU.

Research Involving Special Circumstances

Under special circumstances, alternative arrangements to this policy may be approved on a limited case-by-case basis or by prior agreement.

PIs who leave WVU and do not follow institutional policy and guidance regarding properly notifying WVU OHRP and moving their research may have their protocols at WVU assigned to an authorized PI who is willing to assume this responsibility or closed administratively without further notice.

If a PI goes on an unanticipated leave or there is an abrupt departure from the institution, a modification should be submitted by a current member of the study team as soon as possible to update the PI. If a modification is not going to be submitted, Create and submit the Report New Information SmartForm. Select the category “Failure to follow the protocol due to the action or inaction of the investigator or research staff.” The submission should include an explanation as to why a modification will not be submitted, whether the unanticipated leave is temporary (and for how long) or permanent, and who will be responsible for the conduct of the study during this time.

Other Considerations

Additional institutional requirements exist. The departing PI is responsible for adhering to any applicable institutional policies. For example, if the current PI is leaving the institution and plans to take research data or specimens with them, there are contractual agreements that may be needed in order to share individual level human subjects research data/specimens. These agreements are managed outside of WVU OHRP.

For studies that require continuing review, you will receive automated reminders prompting you to submit. You must submit a Continuing Review SmartForm at least 60 days prior to the expiration date to allow adequate time for review. The IRB cannot ensure continuity of approval if the Continuing Review SmartForm is submitted less than 60 days to expiration. There may be times where 60 days is still insufficient for review if you are making significant changes at continuing review.

If your study is a full board study, please review meeting deadlines. WVU OHRP recommends submitting your continuing review as early as possible with consideration of ancillary reviews (see HRP-309-Worksheet—Ancillary Review (DOCX)) and WVU OHRP staff pre-review.

Complete the Continuing Review SmartForm in WRAP and attach all requested supplements, and have the SmartForm submitted by the PI by clicking the “Submit” activity. Maintain electronic copies of all information submitted to the IRB in case revisions are required.

If the continuing review involves modifications to previously approved research, submit those modifications either as a combined Modification and Continuing Review or as a separate request for modification using the Modification SmartForm.

If the approval of Human Research expires all Human Research procedures related to the protocol under review must cease, including recruitment, advertisement, screening, enrollment, consent, interventions, interactions, and collection or analysis of private identifiable information. Continuing Human Research procedures is a violation of institutional policy.

If current subjects will be harmed by stopping Human Research procedures that are available outside the Human Research context, provide these on a clinical basis as needed to protect current subjects. If current subjects will be harmed by stopping Human Research procedures that are not available outside the Human Research context, submit an RNI associated with the protocol and select “Other.” Provide a written list of the currently enrolled subjects (without PHI), what research procedures are requested to continue for participant safety, and why they will be harmed by stopping Human Research procedures.

Complete the Continuing Review SmartForm in WRAP and attach all requested supplements, and have the SmartForm submitted by the PI by clicking the “Submit” activity. The Continuing Review SmartForm will determine if your IRB submission is eligible for closure based on your responses. Maintain electronic copies of all information submitted to the IRB in case revisions are required. The submission of the Continuing Review SmartForm to close a study is required, even then the study does not require continuing review. Studies should be prompted closed as principal investigators retain their responsibilities while studies are open.

To qualify for closure the following must be true:

1. Study is permanently closed to enrollment OR was never open for enrollment
2. All subjects have completed all study-related interventions OR not applicable (e.g. study did not include interventions, no subjects were enrolled)
3. Collection of private identifiable information is complete OR not applicable (e.g., study did not include collection of private identifiable information, no subjects were enrolled).
4. Analysis of private identifiable information is complete OR not applicable (e.g., study did not include private identifiable information, no subjects were enrolled)

For studies with an external IRB of record, see How do I update my sIRB protocol after it’s approved? for closure instructions.

The following research related events require reporting via an Reportable New Information (RNI) SmartForm submission within 5 business days of becoming aware of any items outlined below.

A research related event may fit into more than more category.

All applicable categories should be selected when submitting RNI SmartForm.

1. Information that indicates a new or increased risk, or a new safety issue. For example:
   1. New information (e.g., an interim analysis, safety monitoring report, publication in the literature, sponsor report, or investigator finding) indicates an increase in the frequency or magnitude of a previously known risk, or uncovers a new risk.
   2. An investigator brochure, package insert, or device labeling is revised to indicate an increase in the frequency or magnitude of a previously known risk, or describe a new risk.
   3. Withdrawal, restriction, or modification of a marketed approval of a drug, device, or biologic used in a research protocol.
   4. Protocol violation that harmed subjects or others or that indicates subjects or others might be at increased risk of harm.
   5. Complaint of a subject that indicates subjects or others might be at increased risk of harm or at risk of a new harm.
   6. Any changes significantly affecting the conduct of the research.
2. Harm experienced by a subject or other individual, which in the opinion of the investigator are unexpected and probably related to the research procedures.
   1. A harm is “unexpected” when its specificity or severity are inconsistent with risk information previously reviewed and approved by the IRB in terms of nature, severity, frequency, and characteristics of the study population.
   2. A harm is “probably related” to the research procedures if in the opinion of the investigator, the research procedures more likely than not caused the harm.
3. Non-compliance with the federal regulations governing human research or with the requirements or determinations of the IRB, or an allegation of such non-compliance.
4. Audit, inspection, or inquiry by a federal agency, sponsor, or other monitoring agency, or WVU compliance group.
5. Written reports of study monitors that identify non-compliance, other issues; local quality improvement review reports.
6. Failure to follow the protocol due to the action or inaction of the investigator or research staff.
7. Breach of confidentiality.
8. Change to the protocol taken without prior IRB review to eliminate an apparent immediate hazard to a subject.
9. Incarceration of a subject in a study not approved by the IRB to involve prisoners.
10. Complaint of a subject that cannot be resolved by the research team.
11. Premature suspension or termination of the protocol by the sponsor, investigator, or institution.
12. Unanticipated adverse device effect (any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects).
13. Information or events which do not fit in any of the above categories.

Complete the RNI SmartForm in WRAP and attach all requested supplements, and have the SmartForm submitted by clicking the “Submit” activity. A linked Modification SmartForm can be submitted concurrently with the RNI submission to address necessary changes or those actions identified in a corrective action plan. Maintain electronic copies of all information submitted to the IRB in case revisions are required.

An RNI should include the following, when applicable:

1. A linked Modification SmartForm if changes are proposed in response to the RNI
2. Sponsor assessment of the event; documentation sponsor was notified
3. Corrective action plan

WVU investigators at times may conduct research at sites that are not owned or operated by this institution. Investigators must provide the IRB with information regarding the facility and population to be recruited. A letter of support from the site where the research will be conducted is required by the IRB. A letter of support is also required of an organizations providing the investigator with private information (e.g. contact information) about their employees, students, etc. for recruitment purposes.

The research location should be added to the applicable SmartForm in WRAP as a Research Location.

The federal Office of Human Research Protections (OHRP) provides guidelines that govern human subjects research in foreign countries, as well as standards from a number of international and regional organizations. The WVU IRB requires researchers comply with these guidelines when conducting international research. For more information regarding these guidelines, visit Health and Human Services: International Compilation of Human Research Standards.

When applicable, the investigator should obtain local IRB or ethics committee approval. If an ethics committee does not exist, a letter of support from a community leader, local partnering organization, or local government should be obtained instead.

Study teams may also need to execute an ancillary review to Export Control. See  HRP-309-Worksheet—Ancillary Review (DOCX) for additional information.

Study teams must seek approval from the appropriate authority to conduct research in a school or to review student records. This documentation, typically a letter of permission on letterhead, must be uploaded under Other Attachments in the IRB submission.

The IRB may approve a research proposal in which an investigator will obtain information or biospecimens for the purpose of screening, recruiting, or determining the eligibility of prospective subjects without the informed consent of the prospective subject or the subject’s legally authorized representative, if either of the following conditions are met:

1. The investigator will obtain information through oral or written communication with the prospective subject or legally authorized representative, OR
2. The investigator will obtain identifiable private information or identifiable biospecimens by accessing records or stored identifiable biospecimens.

The research protocol should include information about how potential subjects will be identified and recruited in order for the IRB to be able to determine whether informed consent for these activities is required.

Contact WVU OHRP with additional questions or for further guidance regarding the requirement to obtain HIPAA authorization or a waiver to obtain HIPAA authorization for recruitment purposes.

WVU students are offered the opportunity to participate in research (as participants) in various ways. Examples include participation for credit as part of a course requirement, for extra credit in a course, or in exchange for payment. A student must not be required to participate in research for course credit unless a comparable non-research alternative is also offered.

To minimize the potential for coercion, alternatives to participating in research for course credit must be comparable in terms of time, effort, and fulfillment of course requirements. Examples include reading and/or writing research papers, attending research presentations offered by faculty, or observing the performance of research projects.

All research participants, including students, must be free to withdraw from participation at any point in a project without penalty. Students who withdraw from a research project for course credit must receive full course credit for participation. When payment is offered, credit for payment should accrue as the project progresses (as appropriate to the research) and should not be contingent upon the student completing the entire project.

Policy and procedures for offering extra credit as an incentive to WVU students for voluntary participation in research

The department wishing to offer extra credit as an incentive to student research participation develops and submits an Extra Credit Policy Plan to WVU OHRP. The WVU IRB Chair Committee reviews and approves the Extra Credit Policy Plan. Upon approval, the department will receive an Extra Credit Policy Approval Letter. After receiving the approval letter, researchers can submit research protocols providing extra credit opportunities to potential student participants. 

When a protocol is submitted for review, the reviewer(s) and/or WVU OHRP staff should verify that an Extra Credit Policy Plan is on file for that department before approval of the protocol. If an Extra Credit Policy Plan is not on file, the reviewer(s) and WVU OHRP staff should inform the PI so that an Extra Credit Policy Plan can be submitted for review, or the extra credit language should be removed from the protocol. To submit an Extra Credit Policy or to request additional information, email irb@mail.wvu.edu.

Departments/Colleges with Approved Extra Credit Policies

• Psychology
• Communications
• Physics-Astronomy
• Political Science
• World Languages Programs
• Social Work
• Chemistry
• Business and Economics

Any cooperative nonexempt human subjects research subject to the Common Rule requires use of single IRB. This requirement applies to that portion of the research that is conducted in the United States. See Appendix A-10 .

For criteria used to determine whether this institution will serve as the sIRB, refer to HRP–833—Worksheet—Considerations for Serving as the sIRB (DOCX).

For criteria used to determine whether this institution will rely on an external IRB, refer to HRP–832—Worksheet—Considerations for Relying on an External IRB (DOCX). An Authorization Agreement(s) must be in place before this IRB can serve as the sIRB or rely on an external IRB.

The WVU IRB determines on a case-by-case basis whether it will serve as the IRB of record. Typically, WVU IRB will only serve as the IRB of record for funded projects subject to the single IRB mandate where WVU is the prime awardee.

The WVU IRB permits reliance on an external IRB for:

• funded projects subjects to a single IRB mandate
• industry funded multi-site projects that are not phase 1

Submit HRP–817—WVU IRB Reliance Request Form to initiate the reliance process.

Once confirmed WVU will cede to the external IRB, submit a New Study SmartForm in the electronic in the electronic IRB system, indicate that an External IRB will serve as the IRB of Record and attach all requested supplements. Have the SmartForm submitted by the PI by clicking the “Submit” activity. Maintain electronic copies of all information submitted to the IRB in case revisions are required.

Protocols overseen by an external IRB where it is discovered the WVU PI did not submit a reliance request and/or did not register and receive acknowledgement from WVU OHRP prior to initiating research activities will be subject to a 90-day PI site-specific hold. This site-specific hold will be communicated to the external IRB of Record and will be in effect until the PI submits the reliance application to WVU and receives acknowledgement to begin human subject research at WVU. Additional requirements may be imposed on a case-by-case basis, at the discretion of the WVU OHRP staff. This will also be reviewed as a reportable event.

If you will request this IRB to serve as the reviewing IRB (sIRB) for cooperative research, contact the WVU OHRP prior to submitting grant or other funding applications to determine whether this IRB will agree to serve as the sIRB for the study.

Submit HRP–817—WVU IRB Reliance Request Form to initiate the reliance process. Once confirmed WVU will serve as the IRB of records, submit New Study SmartForm in the electronic IRB system, indicate if the study is a multi-site or collaborative research study, then select “Yes” to the question “Will your IRB act as the single IRB of record for other participating sites?” Complete the rest of the New Study SmartForm and attach all available supplements. Participating sites are added by executing the “Add Participating Site” activity. Do not initiate this activity until you have received confirmation WVU IRB will serve as the IRB of record. Once confirmed, have the SmartForm submitted by the PI by clicking the “Submit” activity.

WVU OHRP requires submission of these modification types to be submitted for studies with an external IRB of record:

1. Changes in personnel or principal investigator.
2. Changes to a conflict of interest management plan.
3. Changes to HIPAA authorization waivers or alterations

To submit these modifications, submit a Site Modification. Review the step-by-step directions for submitting a Site Modification in the IRB Multi-Site Study Guide, located in the Help Center in WRAP.

For changes that affect the entire study, including non-WVU sites (not required) with an external IRB of record:

Use Update Study Details. This may include updates to the sponsor protocol, investigator brochure, sponsor consent forms, and other items that affect the study across the board. A comment must be added to notify the IRB coordinator of the update.

To close a study with an external IRB of record (required): Use Update Study Details. Indicate the study (or the WVU site) was closed by the external IRB. Include the closure notice. A comment must be added to notify the IRB coordinator of the update.

Review the step-by-step directions for submitting a Study Update in the IRB Multi-Site Study Guide, located in the Help Center in Wrap.

For studies where WVU is the IRB of record, see When is a modification required?

1. Coordinate with HRPP personnel to determine whether this institution’s IRB can act as the single IRB for all or some institutions participating in the study or if an external IRB will assume oversight. To initiate this process, submit HRP–817—WVU IRB Reliance Request Form.
2. Identify whether any IRB fees will be charged for this study and address any budget considerations.
3. Identify all sites that will be engaged in the human research and requiring oversight by the IRB.
4. Ensure that all sites receive a request to rely on the reviewing IRB and that all institutional requirements are satisfied before a study is activated at a relying site.
5. Collaborate with the reviewing IRB to document roles and responsibilities for communicating and coordinating key information from study teams and the IRB or HRPP at relying sites.
6. Respond to questions or information requests from study teams or the IRB or HRPP staff at relying sites.
7. Provide relying site investigators with the policies of the reviewing IRB.
8. Provide relying site investigators with the IRB-approved versions of all study documents, including an approved consent template.
9. Help prepare and submit IRB applications on behalf of all sites. This includes initial review, modifications, personnel updates, reportable new information and continuing review information for all sites.
10. Establish a process for obtaining and collating information from all sites and submitting this information to the reviewing IRB. This includes site-specific variations in study conduct, such as the local consent process and language, subject identification and recruitment processes and local variations in study conduct.
11. Provide pSites with HRP–103p—pSite Manual (DOCX).
12. Fulfill any communication responsibilities as outlined in HRP–830—Worksheet–Communication and Responsibilities (DOCX).
13. Use HRP–811—Form—Basic Site Information, HRP–812—Form—Site Continuing Review, HRP–813—Form—Site Modification, and HRP–814—Form—Site Reportable New Information to collect information from participating sites.
14. Ensure that consent forms used by pSites follow the consent template approved by the reviewing IRB and include required language as specified by the pSites.
15. Provide site investigators with all determinations and communications from the reviewing IRB.
16. Submit reportable new information from pSites to the reviewing IRB in accordance with the terms outlined in the authorization agreement or communication plan.
17. Report the absence of continuing review information from pSites if they do not provide the required information prior to submission of the continuing review materials to the reviewing IRB. Notifying the pSite of their lapse in approval and applicable corrective actions.
18. Provide study records to the relying institution, reviewing IRB or regulatory agencies upon request.

1. Submit the HRP-817—WVU IRB Reliance Request Form to confirm WVU IRB will cede to an external IRB.
2. Submit New Study SmartForm.
3. Obtain appropriate approvals from this institution prior to seeking review by another IRB.
4. Comply with determinations and requirements of the reviewing IRB.
5. Prepare consent and other study documents that are consistent with those approved by the sIRB (e.g., use the approved consent template to create site-specific documents).
6. Provide the reviewing IRB with requested information about local requirements or local research context issues relevant to the IRB’s determination prior to IRB review.
7. Notify the reviewing IRB when local policies that impact IRB review are updated.
8. Cooperate in the reviewing IRB’s responsibility for initial and continuing review, record keeping and reporting and providing all information requested by the reviewing IRB in a timely manner.
9. Disclose conflicts of interest as required by the reviewing IRB and complying with management plans that may result.
10. Promptly report to the reviewing IRB any proposed changes to the research and not implementing those changes to the research without prior IRB review and approval, except where necessary to eliminate apparent immediate hazards to the participants.
11. When enrolling participants, obtain, document and maintain records of consent for each participant or each participant's legally authorized representative.
12. Promptly report to the reviewing IRB any unanticipated problems involving risks to participants or others according to the requirements specified in the reliance agreement.
13. Provide the reviewing IRB with data safety monitoring reports in accordance with the reviewing IRB’s reporting policy.
14. Report non-compliance, participant complaints, protocol deviations or other events according to the requirements specified in the reliance agreement.
15. Specify the contact person and providing contact information for researchers and research staff to obtain answers to questions, express concerns, and convey suggestions regarding the use of the reviewing IRB.
16. Fulfill any communication responsibilities as outlined in HRP–830—WORKSHEET–Communication and Responsibilities (DOCX).
17. Determine which institutional requirements apply to your study and ensure all are met. Refer to HRP–309—Worksheet–Ancillary Review (DOCX).
18. Report updates to WVU IRB using the appropriate method for the type of change (study–wide or local site). See How do I update my sIRB study after it’s approved? for additional information.
19. Close study in WRAP when the study has been closed with the IRB of record.

1. When a subject decides to withdraw from a clinical trial, the investigator conducting the clinical trial should ask the subject to clarify whether the subject wishes to withdraw from all components of the trial or only from the primary interventional component of the trial. If the latter, research activities involving other components of the clinical trial, such as follow-up data collection activities, for which the subject previously gave consent may continue. The investigator should explain to the subject who wishes to withdraw the importance of obtaining follow-up safety data about the subject.
2. Investigators are allowed to retain and analyze already collected data relating to any subject who chooses to withdraw from a research study or whose participation is terminated by an investigator without regard to the subject’s consent, provided such analysis falls within the scope of the analysis described in the IRB-approved protocol. This is the case even if that data includes identifiable private information about the subject.
3. For research not subject to regulation and review by FDA, investigators, in consultation with the funding agency, can choose to honor a research subject’s request that the investigator destroy the subject’s data or that the investigator exclude the subject’s data from any analysis.
4. When seeking the informed consent of subjects, investigators should explain whether already collected data about the subjects will be retained and analyzed even if the subjects choose to withdraw from the research.
5. When research is covered by a certificate of confidentiality, researchers:
   1. May not disclose or provide, in any Federal, State, or local civil, criminal, administrative, legislative, or other proceeding, the name of such individual or any such information, document, or biospecimen that contains identifiable, sensitive information about the individual and that was created or compiled for purposes of the research, unless such disclosure or use is made with the consent of the individual to whom the information, document, or biospecimen pertains; or
   2. May not disclose or provide to any other person not connected with the research the name of such an individual or any information, document, or biospecimen that contains identifiable, sensitive information about such an individual and that was created or compiled for purposes of the research.
   3. May not utilize third parties or entities to collect or store information (e.g., contractors, online platform vendors) that cannot or will not protect against the compelled disclosure of the personally identifiable information.
   4. May disclose information only when:
      1. Required by Federal, State, or local laws (e.g., as required by the Federal Food, Drug, and Cosmetic Act, or state laws requiring the reporting of communicable diseases to State and local health departments), excluding instances of disclosure in any Federal, State, or local civil, criminal, administrative, legislative, or other proceeding.
      2. Necessary for the medical treatment of the individual to whom the information, document, or biospecimen pertains and made with the consent of such individual;
      3. Made with the consent of the individual to whom the information, document, or biospecimen pertains; or
      4. Made for the purposes of other scientific research that is in compliance with applicable Federal regulations governing the protection of human participants in research.
   5. Researchers must inform participants of the protections and limitations of certificates of confidentiality (see language in HRP–502—Template—Consent Document (DOCX)).
   6. For studies that were previously issued a Certificate and notified participants of the protections provided by that Certificate, NIH does not expect participants to be notified that the protections afforded by the Certificate have changed, although IRBs may determine whether it is appropriate to inform participants.
   7. If part of the study cohort was recruited prior to issuance of the Certificate, but are no longer actively participating in the study, NIH does not expect participants consented prior to the change in authority, or prior to the issuance of a Certificate, to be notified that the protections afforded by the Certificate have changed, or that participants who were previously consented be re-contacted to be informed of the Certificate, although the IRB may determine whether it is appropriate to inform participants.
   8. Researchers conducting research covered by a certificate of confidentiality, even if the research is not federally funded, must ensure that if identifiable, sensitive information is provided to other researchers or organizations, the other researcher or organization must comply with applicable requirements when research is covered by a certificate of confidentiality.

1. When a subject withdraws from a study: ^[iii]
   1. The data collected on the subject to the point of withdrawal remains part of the study database and may not be removed.
   2. An investigator may ask a subject who is withdrawing whether the subject wishes to provide continued follow-up and further data collection subsequent to their withdrawal from the interventional portion of the study. Under this circumstance, the discussion with the subject would distinguish between study-related interventions and continued follow-up of associated clinical outcome information, such as medical course or laboratory results obtained through non-invasive chart review, and address the maintenance of privacy and confidentiality of the subject’s information.
   3. If a subject withdraws from the interventional portion of the study, but agrees to continued follow-up of associated clinical outcome information as described in the previous bullet, the investigator must obtain the subject’s informed consent for this limited participation in the study (assuming such a situation was not described in the original informed consent form). IRB approval of informed consent documents is required.
   4. If a subject withdraws from the interventional portion of a study and does not consent to continued follow-up of associated clinical outcome information, the investigator must not access for purposes related to the study the subject’s medical record or other confidential records requiring the subject’s consent.
   5. An investigator may review study data related to the subject collected prior to the subject’s withdrawal from the study, and may consult public records, such as those establishing survival status.
2. For FDA-regulated research involving investigational drugs
   1. Investigators must abide by FDA restrictions on promotion of investigational drugs: ^iv
      1. An investigator, or any person acting on behalf of an investigator, must not represent in a promotional context that an investigational new drug is safe or effective for the purposes for which it is under investigation or otherwise promote the drug.
      2. This provision is not intended to restrict the full exchange of scientific information concerning the drug, including dissemination of scientific findings in scientific or lay media. Rather, its intent is to restrict promotional claims of safety or effectiveness of the drug for a use for which it is under investigation and to preclude commercialization of the drug before it is approved for commercial distribution.
      3. An investigator must not commercially distribute or test market an investigational new drug.
   2. Follow FDA requirements for general responsibilities of investigators ^v
      1. An investigator is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations; for protecting the rights, safety, and welfare of subjects under the investigator's care; and for the control of drugs under investigation.
      2. An investigator must, in accordance with the provisions of 21 CFR §50, obtain the informed consent of each human subject to whom the drug is administered, except as provided in 21 CFR §50.23 or §50.24 of this chapter.
      3. Additional specific responsibilities of clinical investigators are set forth in this part and in 21 CFR §50 and 21 CFR §56.
   3. Follow FDA requirements for control of the investigational drug ^vi
      1. An investigator must administer the drug only to subjects under the investigator's personal supervision or under the supervision of a sub-investigator responsible to the investigator.
      2. The investigator must not supply the investigational drug to any person not authorized under this part to receive it.
   4. Follow FDA requirements for investigator recordkeeping and record retention ^vii
      1. Disposition of drug:
         1. An investigator is required to maintain adequate records of the disposition of the drug, including dates, quantity, and use by subjects.
         2. If the investigation is terminated, suspended, discontinued, or completed, the investigator must return the unused supplies of the drug to the sponsor, or otherwise provide for disposition of the unused supplies of the drug under 21 CFR §312.59.
      2. Case histories.
         1. An investigator is required to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation.
         2. Case histories include the case report forms and supporting data including, for example, signed and dated consent forms and medical records including, for example, progress notes of the physician, the individual's hospital charts, and the nurses' notes. The case history for each individual must document that informed consent was obtained prior to participation in the study.
      3. Record retention:
         An investigator must retain required records for a period of 2 years following the date a marketing application is approved for the drug for the indication for which it is being investigated; or, if no application is to be filed or if the application is not approved for such indication, until 2 years after the investigation is discontinued and FDA is notified.
   5. Follow FDA requirements for investigator reports ^viii
      1. Progress reports: The investigator must furnish all reports to the sponsor of the drug who is responsible for collecting and evaluating the results obtained.
      2. Safety reports: An investigator must promptly report to the sponsor any adverse effect that may reasonably be regarded as caused by, or probably caused by, the drug. If the adverse effect is alarming, the investigator must report the adverse effect immediately.
      3. Final report: An investigator must provide the sponsor with an adequate report shortly after completion of the investigator's participation in the investigation.
      4. Financial disclosure reports:
         1. The clinical investigator must provide the sponsor with sufficient accurate financial information to allow an applicant to submit complete and accurate certification or disclosure statements as required under 21 CFR §54.
         2. The clinical investigator must promptly update this information if any relevant changes occur during the course of the investigation and for 1 year following the completion of the study.
   6. Follow FDA requirements for assurance of IRB review ^ix
      1. An investigator must assure that an IRB that complies with the requirements set forth in 21 CFR §56 will be responsible for the initial and continuing review and approval of the proposed clinical study.
      2. The investigator must also assure that he or she will promptly report to the IRB all changes in the research activity and all unanticipated problems involving risk to human subjects or others, and that he or she will not make any changes in the research without IRB approval, except where necessary to eliminate apparent immediate hazards to human subjects.
   7. Follow FDA requirements for inspection of investigator's records and reports ^x
      1. An investigator must upon request from any properly authorized officer or employee of FDA, at reasonable times, permit such officer or employee to have access to, and copy and verify any records or reports made by the investigator pursuant to 312.62.
      2. The investigator is not required to divulge subject names unless the records of particular individuals require a more detailed study of the cases, or unless there is reason to believe that the records do not represent actual case studies, or do not represent actual results obtained.
   8. Follow FDA requirements for handling of controlled substances ^xi
      1. If the investigational drug is subject to the Controlled Substances Act, the investigator must take adequate precautions, including storage of the investigational drug in a securely locked, substantially constructed cabinet, or other securely locked, substantially constructed enclosure, access to which is limited, to prevent theft or diversion of the substance into illegal channels of distribution.
3. For FDA-regulated research involving investigational devices:
   1. General responsibilities of investigators ^xii
      1. An investigator is responsible for ensuring that an investigation is conducted according to the signed agreement, the investigational plan and applicable FDA regulations, for protecting the rights, safety, and welfare of subjects under the investigator's care, and for the control of devices under investigation. An investigator also is responsible for ensuring that informed consent is obtained in accordance with 21 CFR §50.
   2. Specific responsibilities of investigators ^xiii
      1. Awaiting approval:
         An investigator may determine whether potential subjects would be interested in participating in an investigation, but must not request the written informed consent of any subject to participate, and must not allow any subject to participate before obtaining IRB and FDA approval.
      2. Compliance:
         An investigator must conduct an investigation in accordance with the signed agreement with the sponsor, the investigational plan, and other applicable FDA regulations, and any conditions of approval imposed by an IRB or FDA.
      3. Supervising device use:
         An investigator must permit an investigational device to be used only with subjects under the investigator's supervision. An investigator must not supply an investigational device to any person not authorized to receive it.
      4. Financial disclosure:
         1. A clinical investigator must disclose to the sponsor sufficient accurate financial information to allow the applicant to submit complete and accurate certification or disclosure statements required under 21 CFR §54.
         2. The investigator must promptly update this information if any relevant changes occur during the course of the investigation and for 1 year following completion of the study.
      5. Disposing of device:
         Upon completion or termination of a clinical investigation or the investigator's part of an investigation, or at the sponsor's request, an investigator must return to the sponsor any remaining supply of the device or otherwise dispose of the device as the sponsor directs.
   3. Maintain the following accurate, complete, and current records relating to the investigator's participation in an investigation: ^xiv
      1. All correspondence with another investigator, an IRB, the sponsor, a monitor, or FDA, including required reports.
      2. Records of receipt, use or disposition of a device that relate to:
         1. The type and quantity of the device, the dates of its receipt, and the batch number or code mark.
         2. The names of all persons who received, used, or disposed of each device.
         3. Why and how many units of the device have been returned to the sponsor, repaired, or otherwise disposed of.
      3. Records of each subject's case history and exposure to the device. Case histories include the case report forms and supporting data including, for example, signed and dated consent forms and medical records including, for example, progress notes of the physician, the individual's hospital charts, and the nurses' notes. Such records must include:
         1. Documents evidencing informed consent and, for any use of a device by the investigator without informed consent, any written concurrence of a licensed physician and a brief description of the circumstances justifying the failure to obtain informed consent.
         2. Documentation that informed consent was obtained prior to participation in the study.
         3. All relevant observations, including records concerning adverse device effects (whether anticipated or unanticipated), information and data on the condition of each subject upon entering, and during the course of, the investigation, including information about relevant previous medical history and the results of all diagnostic tests.
         4. A record of the exposure of each subject to the investigational device, including the date and time of each use, and any other therapy.
      4. The protocol, with documents showing the dates of and reasons for each deviation from the protocol.
      5. Any other records that FDA requires to be maintained by regulation or by specific requirement for a category of investigations or a particular investigation.
   4. Inspections ^xv
      1. Entry and inspection: A sponsor or an investigator who has authority to grant access must permit authorized FDA employees, at reasonable times and in a reasonable manner, to enter and inspect any establishment where devices are held (including any establishment where devices are manufactured, processed, packed, installed, used, or implanted or where records of results from use of devices are kept).
      2. Records inspection: A sponsor, IRB, or investigator, or any other person acting on behalf of such a person with respect to an investigation, must permit authorized FDA employees, at reasonable times and in a reasonable manner, to inspect and copy all records relating to an investigation.
      3. Records identifying subjects: An investigator must permit authorized FDA employees to inspect and copy records that identify subjects, upon notice that FDA has reason to suspect that adequate informed consent was not obtained, or that reports required to be submitted by the investigator to the sponsor or IRB have not been submitted or are incomplete, inaccurate, false, or misleading.
   5. Prepare and submit the following complete, accurate, and timely reports ^xvi
      1. Unanticipated adverse device effects. An investigator must submit to the sponsor and to the reviewing IRB a report of any unanticipated adverse device effect occurring during an investigation as soon as possible, but in no event later than 10 working days after the investigator first learns of the effect.
      2. Withdrawal of IRB approval. An investigator must report to the sponsor, within 5 working days, a withdrawal of approval by the reviewing IRB of the investigator's part of an investigation.
      3. Progress. An investigator must submit progress reports on the investigation to the sponsor, the monitor, and the reviewing IRB at regular intervals, but in no event less often than yearly.
      4. Deviations from the investigational plan:
         1. An investigator must notify the sponsor and the reviewing IRB of any deviation from the investigational plan to protect the life or physical well-being of a subject in an emergency.
         2. Such notice must be given as soon as possible, but in no event later than 5 working days after the emergency occurred.
         3. Except in such an emergency, prior approval by the sponsor is required for changes in or deviations from a plan, and if these changes or deviations may affect the scientific soundness of the plan or the rights, safety, or welfare of human subjects, FDA and IRB also is required.
      5. Informed consent. If an investigator uses a device without obtaining informed consent, the investigator must report such use to the sponsor and the reviewing IRB within 5 working days after the use occurs.
      6. Final report. An investigator must, within 3 months after termination or completion of the investigation or the investigator's part of the investigation, submit a final report to the sponsor and the reviewing IRB.
      7. Other. An investigator must, upon request by a reviewing IRB or FDA, provide accurate, complete, and current information about any aspect of the investigation.

1. The clinical trial should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with good clinical practice (GCP) and the applicable regulatory requirements. The rights, safety and well-being of the participants are the most important considerations and should prevail over interests of science and society.
2. Clinical trials should be scientifically sound for their intended purpose and based on adequate and current scientific knowledge and approaches.
   1. The available nonclinical and clinical information on an investigational product(s) should be adequate to support the proposed clinical trial.
   2. Clinical trials should be scientifically sound and reflect the state of knowledge and experience with the investigational product(s), including, if applicable, the condition being treated, diagnosed or prevented; the current understanding of the underlying biological mechanism (of both the condition and the investigational product); and the population for which the investigational product is intended.
   3. There should be periodic review of current scientific knowledge and approaches to determine whether modifications to the trial are needed, since new or unanticipated information may arise once the trial has begun.
3. Investigator's Qualifications and Training
   1. The investigator should be qualified by education, training, and experience to assume responsibility for the proper conduct of the trial, should meet all the qualifications specified by the applicable regulatory requirements, and should provide evidence of such qualifications.
   2. The investigator should be thoroughly familiar with the appropriate use of the investigational product(s), as described in the protocol, in the current Investigator's Brochure, in the product information and/or in other information sources provided by the sponsor.
4. Resources
   1. The investigator should be able to demonstrate (e.g., based on retrospective data) a potential for recruiting the required number of eligible participants within the recruitment period as agreed with the sponsor.
   2. The investigator should have sufficient time, an adequate number of available and qualified staff, and adequate facilities for the foreseen duration of the trial to conduct the trial properly and safely.
5. Responsibilities
   1. The investigator may delegate trial-specific activities to other persons or parties. The investigator may be supported by the sponsor in the identification of a suitable service provider(s); however, the investigator retains the final decision on whether the service provider intended to support the investigator is appropriate based on information provided to the sponsor. The investigator retains the ultimate responsibility and should maintain appropriate oversight of the persons or parties undertaking the activities delegated to ensure the rights, safety and well-being of the trial participants and reliability of the data. The level of investigator oversight of the delegated activities should depend on the nature of the delegated activities and be proportionate to the importance of the data being protected and the risks to trial participant safety and data reliability.
   2. The investigator should ensure that all persons or parties to whom the investigator has delegated trial-related activities are appropriately qualified and are adequately informed about the relevant aspects of the protocol, the investigational product(s), and their assigned trial activities (including activities conducted by staff provided by other parties in accordance with local regulatory requirements). Trial-related training to persons assisting in the trial should correspond to what is necessary to enable them to fulfill their delegated trial activities that go beyond their usual training and experience.
   3. The investigator should ensure a record is maintained of the persons and parties to whom the investigator has delegated trial-related activities. Documentation of delegation should be proportionate to the significance of the trial-related activities. In situations where the activities are performed as part of clinical practice, delegation documentation may not be required.
   4. Agreements made by the investigator/institution with service providers for trial-related activities should be documented.
   5. The investigator/institution should permit monitoring and auditing by the sponsor, inspection by the appropriate regulatory authority(ies) and, in accordance with applicable regulatory requirements, review by IRB(s).
6. Communication with IRB
   1. Submission to the IRB may be made by the investigator/institution or sponsor in accordance with applicable regulatory requirements.
   2. Before initiating a trial, the investigator/institution should have a documented and dated approval from the IRB for the trial protocol, informed consent materials, participant recruitment procedures (e.g., advertisements), and any other trial-related information to be provided to participants.
   3. As part of the investigator's/institution’s or sponsor’s (in accordance with applicable regulatory requirements) submission to the IRB, a current copy of the Investigator's Brochure or basic product information brochure should be provided. If the Investigator's Brochure or basic product information brochure is updated during the trial, the IRB should receive the current version in accordance with applicable regulatory requirements.
   4. As the trial progresses, the investigator/institution or sponsor should provide any updates to the participant information to the IRB in accordance with applicable regulatory requirements.
   5. The investigator or sponsor should submit documented summaries of the trial status to the IRB in accordance with local regulatory requirements or upon request.
   6. The investigator or the sponsor should promptly communicate to the IRB and where applicable, to the institution any changes significantly affecting the conduct of the trial and/or increasing risk to participants.
7. Compliance with Protocol
   1. The investigator/institution should sign the protocol, or an alternative contract, to confirm agreement with the sponsor.
   2. The investigator/institution should comply with the protocol, GCP and applicable regulatory requirements.
   3. The investigator should document all protocol deviations. In addition to those identified by the investigator themselves, protocol deviations related to their trial participants and their conduct of the trial may be communicated to them by the sponsor. In either case, the investigator should review the deviations, and for those deviations deemed important, the investigator should explain the deviation and implement appropriate measures to prevent a recurrence, when applicable.
   4. The investigator should follow the protocol and deviate only where necessary to eliminate an immediate hazard(s) to trial participants. In case of deviations undertaken to eliminate immediate hazard to trial participants, the investigator should inform the sponsor promptly.
   5. The investigator should report information on the immediate hazard, the implemented change and the subsequent proposed protocol amendment, if any, to the IRB and, where applicable, regulatory authorities.
8. Premature Termination or Suspension of a Trial
   1. If the trial is prematurely terminated or suspended for any reason, the investigator/institution should promptly inform the trial participants and should assure appropriate therapy and follow-up for the participants.
   2. Where the investigator terminates or suspends their involvement in a trial without prior agreement by the sponsors, the investigator should promptly inform the institution, where applicable, the sponsor, the IRB, and the regulatory authorities in accordance with applicable regulatory requirements and should provide a detailed explanation of the reasons.
   3. If the sponsor terminates or suspends a trial, the investigator/institution, or the sponsor, in accordance with applicable regulatory requirement(s), should promptly inform the IRB and the regulatory authorities and should provide an appropriate explanation.
   4. If the IRB terminates or suspends its approval of a trial, the investigator should inform the institution, where applicable, and the investigator/institution should promptly notify the sponsor.
9. Participant Medical Care and Safety Reporting
   1. Medical Care of Trial Participants
      1. A qualified physician or, where appropriate, a qualified dentist (or other qualified healthcare professionals in accordance with local regulatory requirements) who is an investigator or a sub-investigator for the trial, should have the responsibility for trial-related medical care and decisions.
      2. Other appropriately qualified healthcare professionals may be involved in the medical care of trial participants, in line with their normal activities and in accordance with local regulatory requirements.
      3. During and following participation in a trial, the investigator/institution should ensure that adequate medical care is provided to a participant for any adverse events, including clinically significant laboratory values, related to the trial. The investigator/institution should inform a participant when medical care is needed for intercurrent illness(es) of which the investigator becomes aware.
      4. The investigator should inform the participant’s primary physician about the participant’s involvement in the trial if the participant has a primary physician and agrees to the primary physician being informed.
   2. Safety Reporting
      1. Adverse events and/or abnormal test results required for safety evaluations (as outlined in the protocol) should be reported to the sponsor according to the reporting requirements and within the time periods specified in the protocol. Unfavorable medical events occurring in participants before investigational product administration (e.g., during screening) should be considered and reported to the sponsor if required by the protocol.
      2. All serious adverse events (SAEs) should be reported immediately (after the investigator reasonably becomes aware of the event) to the sponsor. The investigator should also include an assessment of causality. In accordance with applicable regulatory requirements, the protocol may identify SAEs not requiring immediate reporting, for example, deaths or other events that are endpoints. Subsequent information should be submitted as a follow-up report, as necessary.
      3. For reported deaths, the investigator should supply the sponsor, the IRB and, where applicable, the regulatory authority with any additional requested information (e.g., autopsy reports and terminal medical reports) when they become available.
      4. The investigator may delegate activities for safety reporting to qualified investigator site staff but retains the overall responsibility for safety of participants under their responsibility and compliance with the reporting requirements.
10. Informed Consent of Trial Participants
    1. In obtaining and documenting informed consent (paper or electronic format), the investigator should comply with the applicable regulatory requirements and should adhere to GCP and to the ethical principles that have their origin in the Declaration of Helsinki. The informed consent process should include the following:
       1. Prior to consenting and enrolling participants, the investigator should have the IRB's documented approval of the informed consent materials and process.
       2. The information should be as clear and concise as possible, use simple language and avoid unnecessary volume and complexity. This is to ensure that the trial participants or their legally acceptable representatives have an adequate understanding of the objectives of the trial, alternative treatments, potential benefits and risks, burdens, their rights, and what is expected of the participants to be able to make an informed decision as to their participation in the trial.
       3. Varied approaches (e.g., text, images, videos and other interactive methods), may be used in the informed consent process including for providing information to the participant. The characteristics of the potential trial population (e.g., participants may lack familiarity with computerized systems) and the suitability of the method of obtaining consent should be taken into consideration when developing the informed consent materials and process. When computerized systems are used to obtain informed consent, trial participants may be given the option to use a paper-based approach as an alternative.
       4. Obtaining consent remotely may be considered where appropriate.
       5. Whether the informed consent process takes place in person or remotely, the investigator should assure themselves of the identity of the participant (or legally acceptable representative) in accordance with applicable regulatory requirements.
    2. The participant or the participant’s legally acceptable representative should be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue trial participation. The communication of this information and confirmation of the willingness to continue trial participation should be documented. New information that could impact a participant’s willingness to continue participation should be assessed to determine if re-consent is needed. If re-consent is needed, new information should be clearly identified in the revised informed consent materials. Revised informed consent materials should receive the IRB’s approval in advance of use.
    3. Neither the investigator, nor the investigator site staff, should coerce or unduly influence a participant to participate or to continue their participation in a trial.
    4. None of the information provided to the participant or the participant’s legally acceptable representative during the informed consent process should contain any language that causes the participant to waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution, the sponsor, or their service providers from liability for negligence.
    5. The informed consent process should be conducted by the investigator or other investigator site staff delegated by the investigator, in accordance with applicable regulatory requirements. If the participant is unable to provide consent themselves (e.g., minors, patients with severely impaired decision-making capacity), the participant’s legally acceptable representative should provide their consent on behalf of the participant.
    6. The information provided during the informed consent process and translations should be relevant, clear, simple, concise and understandable to the participant or the participant’s legally acceptable representative and the impartial witness, where applicable.
    7. Before informed consent may be obtained, the investigator, or investigator site staff delegated by the investigator, should provide the participant or the participant’s legally acceptable representative ample time and opportunity to inquire about trial details and to decide whether or not to participate in the trial.
    8. Prior to trial participation, the informed consent form should be signed and dated by the participant or by the participant’s legally acceptable representative, where appropriate, by an impartial witness and by the investigator or delegated investigator site staff who conducted the informed consent discussion.
    9. In emergency situations, when prior consent of the participant is not possible, the consent of the participant’s legally acceptable representative, if present, should be requested. When prior consent of the participant is not possible and the participant’s legally acceptable representative is not available, enrollment of the participant should require measures described in the protocol and/or elsewhere, with documented approval by the IRB, to protect the participant’s rights, safety and well-being and to ensure compliance with applicable regulatory requirements.
    10. If a participant or the legally acceptable representative is unable to read, an impartial witness should be present during the entire informed consent discussion. After the informed consent form and any other information is read and explained to the participant or the participant’s legally acceptable representative, and they have orally consented, the witness should sign and date the consent form.
    11. The informed consent discussion and the informed consent materials to be provided to participant should explain the following as applicable:
        1. The purpose of the trial;
        2. That the trial involves research and summary of the experimental aspects of the trial;
        3. The trial’s investigational product(s) and the probability for random assignment to the investigational product, if applicable;
        4. The trial procedures to be followed, including all invasive procedures;
        5. What is expected of the participants;
        6. The reasonably foreseeable risks or inconveniences to the participant and, when applicable, the participant’s partner, to an embryo, fetus, or nursing infant;
        7. The reasonably expected benefits. When there is no intended clinical benefit to the participant, the participant should be made aware of this;
        8. The alternative procedure(s) or course(s) of treatment that may be available to the participant, and their important potential benefits and risks;
        9. The compensation and/or treatment available to the participant in the event of trial related injury;
        10. Any anticipated prorated compensation to the participant for trial participation;
        11. Any anticipated expenses to the participant for trial participation;
        12. That the participant’s trial participation is voluntary, and the participant may decide to stop taking the investigational product or withdraw from the trial, at any time, without penalty or loss of benefits to which the participant is otherwise entitled;
        13. The follow-up procedure for participants who stopped taking the investigational product, withdrew from the trial or were discontinued from the trial;
        14. That by agreeing to participant in the trial, the participant or their legally acceptable representative allows direct access to source records, based on the understanding that the confidentiality of the participant’s medical record will be safeguarded. This access is limited for the purpose of reviewing trial activities and/or reviewing or verifying data and records by the regulatory authority(ies) and the sponsor’s representatives, for example, monitor(s) or auditor(s), and in accordance with applicable regulatory requirements, IRB;
        15. That records identifying the participant will be kept confidential and, to the extent permitted by the applicable regulatory requirements, will not be made publicly available. If the results of the trial are published, the participant’s identity will remain confidential. The trial may be registered on publicly accessible and recognized databases, per applicable regulatory requirements;
        16. That the participant or the participant’s legally acceptable representative will be informed in a timely manner if information becomes available that may be relevant to the participant’s willingness to continue trial participation;
        17. The person(s) to contact for further trial information and the trial participant’s rights, and whom to contact in the event of suspected trial-related injury;
        18. The foreseeable circumstances and/or reasons under which the participant’s trial participation may be terminated;
        19. The expected duration of the participant’s trial participation;
        20. The approximate number of participants involved in the trial;
        21. That trial results and information on the participant’s actual treatment, if appropriate, will be made available to them should they desire it when this information is available from the sponsor.
    12. Prior to participation, the participant or the participant’s legally acceptable representative should receive a copy (paper or electronic) of the signed informed consent form and any other informed consent materials provided, in accordance with applicable regulatory requirements. During trial participation, the participant or the participant’s legally acceptable representative should receive a copy of the consent form updates and any other updated informed consent materials provided.
    13. When a minor is to be included as a participant, age-appropriate assent information should be provided and discussed with the minor as part of the consent process, and assent from the minor to enroll in the trial should be obtained as appropriate. As process for re-consent should be considered if, during the course of the trial, the minor reaches the age of legal consent, in accordance with applicable regulatory requirements.
    14. When a clinical trial includes participant who may only be enrolled in the trial with the consent of the participant’s legally acceptable representative, the participants should be informed about the trial in a manner that facilitates their understanding and, if capable, the participant should sign and date the informed consent form or assent form as appropriate.
11. End of Participation in a Clinical Trial
    1. When a participant decides to stop treatment with the investigational product, stop trial visits or completely withdraw from a trial; is discontinued from the trial; or reaches the routine end of the trial, the investigator should follow the protocol and other sponsor instructions to determine appropriate follow-up measures. This may include instructions to avoid unnecessary loss of already collected critical data in accordance with applicable regulatory requirements.
    2. Although a participant is not obliged to provide a reason(s) for withdrawing prematurely from a trial, the investigator should make a reasonable effort to ascertain the reason(s), while fully respecting the participant’s rights. The investigator should consider if a discussion with the participant or the participant’s legally acceptable representative is appropriate. This discussion should focus on the reasons for withdrawal to determine if there are ways to address the concerns such that the participant could reconsider withdrawal without unduly influencing the participant’s decision. The investigator or delegated investigator site staff should consider explaining to the participant the value of continuing their participation to minimize trial participants withdrawal. In this process, the investigator should ensure that it does not interfere with the participant’s decision to refuse or withdraw participation at any time.
    3. Where relevant, the investigator should inform the participant about the trial results and treatment received when this information is available from the sponsor after unblinding, with due respect to the participant’s preference to be informed.
12. Investigational Product Management
    1. Responsibility for investigational product(s), including accountability, handling, dispensing, administration and return, rests with the investigator/institution. The sponsor may facilitate aspects of investigational product management (e.g., by providing forms and technical solutions, such as computerized systems, and arranging distribution of investigational product to trial participants).
    2. When the investigator/institution delegates some or all of their activities for investigational product(s) management to a pharmacist or another individual in accordance with local regulatory requirements, the delegated individual should be under the oversight of the investigator/institution.
    3. Where the investigator has delegated activities related to investigational product management or aspects of these activities have been facilitated by the sponsor, the level of investigator oversight will depend on a number of factors, including the characteristics of the investigational product, route and complexity of administration, level of existing knowledge about the investigational product’s safety and marketing status.
    4. The investigator/institution and/or pharmacist or other appropriate individual, should maintain records of the product’s delivery, the inventory, the use by each participant (including documenting that the participants were provided the doses specified by the protocol), and the return to the sponsor and destruction or alternative disposition of unused product(s). These records should include dates, quantities, batch/serial numbers, expiration dates (if applicable), and the unique code numbers assigned to the investigational product(s) and trial participants. For authorized medicinal products, alternative approaches to the aforementioned may be considered, in accordance with local regulatory requirements.
    5. The investigator should ensure that the investigational product(s) are used only in accordance with the approved protocol.
    6. When applicable, the investigator or a person designated by the investigator/institution should explain the correct use of the investigational product(s) to each participant and should check, at intervals appropriate for the trial, that each participant is following the instructions properly.
    7. The investigational product may be shipped to the participant’s location or supplied to/dispensed at a location closer to the participant (e.g., at a local pharmacy or local healthcare center). The investigational product may be administered at the participant’s location by investigator site staff, the participant themselves, or a caregiver or a healthcare professional.
    8. Investigational product management should be arranged and conducted in accordance with applicable regulatory requirements, and safeguards should be in place to ensure product integrity, product use per protocol and participant safety.
13. Randomization Procedures and Unblinding
    1. The investigator should follow the trial’s randomization procedures, if any, and in the case of an investigator-blinded trial, should ensure that the treatment randomization code is broken only in accordance with the protocol. In the case of an emergency, to protect participant safety, the investigator should be prepared and capable from the start of the trial to perform unblinding without undue delay and hinderance. The investigator should promptly document and explain to the sponsor any premature unblinding (e.g., accidental unblinding, emergency unblinding to protect trial participant, unblinding due to an SAE) of the investigational product(s).
14. Records
    1. In generating, recording and reporting trial data, the investigator should ensure the integrity of data under their responsibility, irrespective of the media used.
    2. The investigator/institution should maintain adequate source records that include pertinent observations on each of the trial participants under their responsibility. Source records should be attributable, legible, contemporaneous, original, accurate and complete. Changes to source records should be traceable, should not obscure the original entry and should be explained if necessary (via an audit trail). The investigator should define what is considered to be a source record(s), the methods of data capture and their location prior to starting the trial and should update this definition when needed. Unnecessary transcription steps in between the source record and the data acquisition tool should be avoided.
    3. The investigator should be provided with timely access to data by the sponsor and be responsible for the timely review of data, including relevant data from external sources that can have an impact on, for example, participant eligibility, treatment or safety (e.g., central laboratory data, centrally read imaging data, other institution’s records and, if appropriate, electronic patient-reported outcome (ePRO) data. The protocol may provide exceptions for access, for instance, to protect blinding.
    4. The investigator should ensure that data acquisition tools and other systems deployed by the sponsor are used as specified in the protocol or trial-related instructions.
    5. The investigator should ensure the accuracy, completeness, legibility and timeliness of the data reported to the sponsor in the data acquisition tools completed by the investigator site (e.g., case report form (CRF)) and in any other required reports (e.g., SAE reports). The investigator should review and endorse the reported data at important milestones agreed upon with the sponsor (e.g., interim analysis).
    6. Data reported to the sponsor should be consistent with the source records or the discrepancies explained. Changes or corrections in the reported data should be traceable, should be explained (if necessary) and should not obscure the original entry.
    7. The investigator/institution should implement appropriate measures to protect the privacy and confidentiality of personal information or trial participants in accordance with applicable regulatory requirements on personal data protection.
    8. Data reported to the sponsor should be identified by an unambiguous participant code that can be tracked back to the identity of the participant by the investigator/institution.
    9. For systems deployed by the investigator/institution that maintain and retain trial data/information, the investigator/institution should ensure that such data are protected from unauthorized access, disclosure, dissemination or alteration and from inappropriate destruction or accidental loss.
       
    10. When using computerized systems in a clinical trial, the investigator/institution should do the following:
        1. For systems deployed by the investigator/institution, ensure that appropriate individuals have secure and attributable access;
        2. For systems deployed by the sponsor, notify the sponsor when access permissions need to be changed or revoked from an individual;
        3. For system deployed by the investigator/institution specifically for the purposes of clinical trials, ensure the requirements for computerized systems in section 4 of ICH GCP Annex 1 ^[xvii] are addressed proportionate to the risks to participants and to the importance of the data;
        4. Where equipment for data acquisition is provided to trial participants by the investigator, ensure that traceability is maintained and participants are provided with appropriate training;
        5. Ensure that incidents in the use and operation of computerized systems, which in the investigator/institution’s judgment may have a significant and/or persistent impact on the trial data or system security, are reported to the sponsor and, where applicable, to the IRB.
    11. The investigator/institution should maintain the trial records as specified in Appendix C of ICH GCP Annex 1 and as required by the applicable regulatory requirement(s). The investigator/institution should have control of all essential records generated by the investigator/institution before and during the conduct of the trial.
    12. The investigator/institution should retain the essential records for the required retention period in accordance with applicable regulatory requirements or until the sponsor informs the investigator/institution that these records are no longer needed, whichever is the longest. The investigator/institution should take measures to ensure availability, accessibility and readability and to prevent unauthorized access and accidental or premature destruction of these records.
    13. The investigator/institution should keep the sponsor informed of the name of the person responsible for maintaining the essential records during the retention period; for example, when the investigator site closes or an investigator leaves the site.
    14. Upon request of the monitor, auditor, IRB, or regulatory authority, the investigator/institution should make available for direct access all requested trial-related records.
15. Reports
    1. Upon completion of the trial, the investigator, where applicable, should inform the institution. The investigator/institution should provide the IRB with a summary of the trial’s outcome, and, if applicable, the regulatory authorities with any required reports.

(See DOE Order 443.1C, Chg 1)

1. Research that involves one or more of the following must be submitted to the appropriate IRB for human subjects research (HSR)/not HSR review and determination:
   1. Study of humans in a systematically modified environment. These studies include but are not limited to intentional modification of the human environment:
      1. Study of human environments that use tracer chemicals, particles or other materials to characterize airflow.
      2. Study in occupied homes or offices that:
         1. Manipulate the environment to achieve research aims.
         2. Test new materials.
         3. Involve collecting information on occupants’ views of appliances, materials, or devices installed in their homes or their energy-saving behaviors through surveys and focus groups.
   2. Use of social media data and/or other publicly available data about individuals or publicly available biospecimens, even if the data or biospecimens appear(s) to be de-identified. Note: DOE follows the Health Insurance Portability and Accountability Act (HIPAA) and guidance issued by the National Institutes of Standards and Technology, as a minimum, in determining identifiability.
   3. Human Terrain Mapping (HTM), which is managed as HSR. HTM must be strictly limited to only those projects involving the analysis and modeling of de-identified data.
2. Ensure that final HSR/not HSR determinations for studies that may constitute HSR, including exempt HSR determinations, are made through the appropriate IRB and/or IRB office. For sites that use one or both Central DOE IRB(s) as their IRB(s) of record, the Central DOE office is the responsible office and coordinates with the site HSR leads, as appropriate, to discuss project specific information and convey study determinations.
3. If you submit studies to DOE central or DOE site IRBs, complete additional DOE-specific training that includes a module on recognizing and addressing bias in the design, review and conduct of Human Research.
4. Personally identifiable information (PII) collected and/or used during HSR projects must be protected in accordance with the requirements of DOE Order 206.1, Department of Energy Privacy Program, current version. The Central DOE IRBs require submission of DOE’s HRP–490—Checklist—Reviewing Protocols that use Personally Identifiable Information (PII) if your research includes PII. Contact the CDOE at CDOEIRB@orau.org to obtain a copy.
5. The following must be reported in writing to the DOE human subjects research Program Manager (and, when a National Nuclear Security Administration (NNSA) element is involved, the NNSA HSP Program Manager), even for HSR that meets the regulatory definition of exempt HRS as outlined in 10 Code of Federal Regulations (CFR) Part 745.104.
   1. Prior to initiation of the HSR portion of a new project, involving:
      1. An institution without an established Institutional Review Board (IRB);
      2. A foreign country;
      3. The potential for significant controversy (e.g., negative press or reaction from stakeholder or oversight groups);
      4. Research subjects in a protected class (including the populations identified in Subparts B, C, and D of 45 CFR Part 46), as well as other such as individuals with impaired decision-making capability, or DOE/NNSA Federal or DOE/NNSA contractor employees as human subjects, who may be more vulnerable to coercion and undue influence to participate) that is outside of the reviewing IRB’s typical range/scope; or
      5. The generation or use of classified information.
   2. Immediately upon a finding of a suspected or confirmed data breach involving PII in printed or electronic form, report to the IRB, the DOE/NNSA HSP Program Manager(s), and the Integrated Joint Cybersecurity Coordination Center (iJC3), in accordance with the requirements of DOE O 206.1. The appropriate HSP Program Manager must also be notified of any corrective actions taken and consulted regarding the plan for any remaining corrective actions.
   3. Immediately upon learning of a serious adverse event, report to the IRB and the DOE/NNSA HSP Program Manager(s). The appropriate HSP Program Manager must also be notified of any corrective actions taken and consulted regarding the plan for any remaining corrective actions.
   4. The IRB must be notified immediately and the DOE HSP Program Manager (and, when an NNSA element is involved, the NNSA HSP Program Manager) must be notified within two (2) business days of learning of the following and consulted regarding planned corrective actions if any of the following occur:
      1. Unanticipated problems, significant adverse events, and complaints about the research.
      2. Any suspension or termination of IRB approval of research.
      3. Any known or potential incidents of non-compliance with requirements of DOE Order 443.1C, Chg.1, 10 CFR Part 745, or 45 CFR Part 46.
6. Requirements for human participant protections for classified research apply to all classified research conducted or supported by the DOE and its national laboratories, including contracts, and including Human Terrain Mapping research.
7. Researchers conducting human subjects research in any other country or on citizens or other individuals residing in that country must be cognizant of country-specific human subjects research requirements and consult the IRB regarding applicability of such requirements.
8. No human subjects research conducted with DOE funding, at DOE institutions (regardless of funding source), or by DOE or DOE contractor personnel (regardless of funding source or location conducted), whether done domestically or in an international environment, including classified and proprietary research, may be initiated without both a Federalwide Assurance (FWA) or comparable assurance (e.g., Department of Defense assurance) of compliance and approval by the cognizant Institutional Review Board (IRB) in accordance with 10 CFR §745.103.
9. Human subjects research involving multiple DOE sites (e.g., members of the research team from more than one DOE site and/or data or human subjects from more than one DOE site) must be reviewed and approved by one of the Central DOE IRBs prior to initiation, or if authorized by the DOE and/or NNSA HSP Program Manager, other appropriate IRB of record. In all cases, an IRB Authorization Agreement (IAA) or Memorandum of Understanding (MOU) must be in place between the organization(s) conducting the HSR and the organization responsible for IRB review.
10. Human subjects research that involves targeted inclusion of DOE Federal and/or contractor employees or their data must first be reviewed and approved by the appropriate DOE IRB (the DOE site IRB or one of the Central DOE IRBs), or if deemed more fitting by the Federally assured DOE site or Headquarters, other appropriate IRB of record, in accordance with an IAA or MOU negotiated between the DOE site or Headquarters and the organization responsible for IRB review.
11. Classified and unclassified intelligence and intelligence–related HSR regardless of the funding source (including, but not limited to, Strategic Intelligence Partnership Program (SIPP) funded studies, DOE Office of Intelligence and Counterintelligence (DOE-IN) funded studies, and/or studies funded by other DOE program offices that use intelligence datasets), must be reviewed and approved by the Central DOE IRB–Classified.
12. If applicable, federally funded HSR must comply with the requirements of the Paperwork Reduction Act.
13. If applicable, HSR involving visiting student researchers, researchers, and scholars from other countries as members of research teams must comply with Department of State requirements, e.g., those outlined in 22 CFR Part 62, Exchange Visitor Program, and U.S. Department of State Guidance Directive 2024–01, current version.
14. Equitable payment of human subjects participating in HSR is allowable.
15. Other specific requirements of the DOE research can be found in the “Additional Requirements for Department of Energy (DOE) Research” section in the IRB’s HRP–318—Worksheet—Additional Federal Agency Criteria (DOCX).

Additional Requirements for DOJ Research conducted in the Federal Bureau of Prisons

1. Implementation of Bureau programmatic or operational initiatives made through pilot projects is not considered to be research.
2. The project must not involve medical experimentation, cosmetic research, or pharmaceutical testing.
3. The research design must be compatible with both the operation of prison facilities and protection of human subjects.
4. Investigators must observe the rules of the institution or office in which the research is conducted.
5. Any investigator who is a non-employee of the Bureau of Prisoners must sign a statement in which the investigator agrees to adhere to the requirements of 28 CFR §512.
6. The research must be reviewed and approved by the Bureau Research Review Board.
7. Incentives cannot be offered to help persuade inmate subjects to participate. However, soft drinks and snacks to be consumed at the test setting may be offered. Reasonable accommodations such as nominal monetary recompense for time and effort may be offered to non-confined research subjects who are both:
   1. No longer in Bureau of Prisons custody.
   2. Participating in authorized research being conducted by Bureau employees or contractors.
8. A non-employee of the Bureau may receive records in a form not individually identifiable when advance adequate written assurance that the record will be used solely as a statistical research or reporting record is provided to the agency.
9. Except as noted in the consent statement to the subject, you must not provide research information that identifies a subject to any person without that subject’s prior written consent to release the information. For example, research information identifiable to a particular individual cannot be admitted as evidence or used for any purpose in any action, suit, or other judicial, administrative, or legislative proceeding without the written consent of the individual to whom the data pertain.
10. Except for computerized data records maintained at an official Department of Justice site, records that contain non–disclosable information directly traceable to a specific person may not be stored in, or introduced into, an electronic retrieval system.
11. If you are conducting a study of special interest to the Office of Research and Evaluation but the study is not a joint project involving Office of Research and Evaluation, you may be asked to provide Office of Research and Evaluation with the computerized research data, not identifiable to individual subjects, accompanied by detailed documentation. These arrangements must be negotiated prior to the beginning of the data collection phase of the project.
12. Required elements of disclosure additionally include:
    1. Identification of the investigators.
    2. Anticipated uses of the results of the research.
    3. A statement that participation is completely voluntary and that the subject may withdraw consent and end participation in the project at any time without penalty or prejudice (the inmate will be returned to regular assignment or activity by staff as soon as practicable).
    4. A statement regarding the confidentiality of the research information and exceptions to any guarantees of confidentiality required by federal or state law. For example, an investigator may not guarantee confidentiality when the subject indicates intent to commit future criminal conduct or harm himself or herself or someone else, or, if the subject is an inmate, indicates intent to leave the facility without authorization.
    5. A statement that participation in the research project will have no effect on the inmate subject's release date or parole eligibility.
13. You must have academic preparation or experience in the area of study of the proposed research.
14. The IRB application must include a summary statement, which includes:
    1. Names and current affiliations of the investigators.
    2. Title of the study.
    3. Purpose of the study.
    4. Location of the study.
    5. Methods to be employed.
    6. Anticipated results.
    7. Duration of the study.
    8. Number of subjects (staff or inmates) required and amount of time required from each.
    9. Indication of risk or discomfort involved as a result of participation.
15. The IRB application must include a comprehensive statement, which includes:
    1. Review of related literature.
    2. Detailed description of the research method.
    3. Significance of anticipated results and their contribution to the advancement of knowledge.
    4. Specific resources required from the Bureau of Prisons.
    5. Description of all possible risks, discomforts, and benefits to individual subjects or a class of subjects, and a discussion of the likelihood that the risks and discomforts will actually occur.
    6. Description of steps taken to minimize any risks.
    7. Description of physical or administrative procedures to be followed to: Ensure the security of any individually identifiable data that are being collected for the study.
    8. Destroy research records or remove individual identifiers from those records when the research has been completed.
    9. Description of any anticipated effects of the research study on institutional programs and operations.
    10. Relevant research materials such as vitae, endorsements, sample consent statements, questionnaires, and interview schedules.
16. The IRB application must include a statement regarding assurances and certification required by federal regulations, if applicable.
17. You must assume responsibility for actions of any person engaged to participate in the research project as an associate, assistant, or subcontractor.
18. At least once a year, you must provide the Chief, Office of Research and Evaluation, with a report on the progress of the research.
19. At least 12 working days before any report of findings is to be released, you must distribute one copy of the report to each of the following: the chairperson of the Bureau Research Review Board, the regional director, and the warden of each institution that provided data or assistance.
20. You must include an abstract in the report of findings.
21. In any publication of results, you must acknowledge the Bureau's participation in the research project.
22. You must expressly disclaim approval or endorsement of the published material as an expression of the policies or views of the Bureau.
23. Prior to submitting for publication the results of a research project conducted under this subpart, you must provide two copies of the material, for informational purposes only, to the Chief, Office of Research and Evaluation, Central Office, Bureau of Prisons.
24. Other specific requirements of the Department of Justice (DOJ) Research Conducted within the Federal Bureau of Prisons (BOP) can be found in the “Additional Requirements for Department of Justice (DOJ) Research Conducted within the Federal Bureau of Prisons (BOP)” section in the IRB’s HRP–318—Worksheet—Additional Federal Agency Criteria (DOCX).

1. Each school at which the research is conducted must provide an assurance that they comply with the Family Educational Rights and Privacy Act (FERPA) and the Protection of Pupil Rights Amendment (PPRA).
2. Provide a copy of all surveys and instructional material used in the research. Upon request parents of children ^xix involved in the research ^xx must be able to inspect these materials.
3. The school in which the research is being conducted must have policies regarding the administration of physical examinations or screenings that the school may administer to students.
4. Other specific requirements of the Department of Education (ED) Research can be found in the “Additional Requirements for Department of Education (ED) Research” section in the IRB’s HRP–318—Worksheet—Additional Federal Agency Criteria (DOCX).

1. Research conducted, supported, or intended to be submitted to EPA is subject to Environmental Protection Agency Regulations.
2. Intentional exposure of pregnant women or children to any substance is prohibited.
3. Observational research involving pregnant women and fetuses are subject to additional DHHS requirements for research involving pregnant women (45 CFR §46 Subpart B) and additional DHHS requirements for research involving children (45 CFR §46 Subpart D.)
4. Research involving children must meet category #1 or #2.
5. Other specific requirements of the Environmental Protection Agency (EPA) Research can be found in the “Additional Requirements for Environmental Protection Agency (EPA) Research and Research Intended to be Submitted to the Environmental Protection Agency” section in the IRB’s HRP–318—Worksheet—Additional Federal Agency Criteria (DOCX).

1. That National Institutes of Health expects that all sites participating in multi-site studies involving non-exempt human subjects research funded by the NIH will use a single Institutional Review Board (sIRB) to conduct the ethical review required by the Department of Health and Human Services regulations for the Protection of Human Subjects at 45 CFR Part 46.
   1. This policy applies to the domestic sites of NIH-funded multi-site studies where each site will conduct the same protocol involving non-exempt human subjects research, whether supported through grants, cooperative agreements, contracts, or the NIH Intramural Research Program. It does not apply to career development, research training or fellowship awards.
   2. This policy applies to domestic awardees and participating domestic sites. Foreign sites participating in NIH-funded, multi-site studies will not be expected to follow this policy.
   3. Exceptions to the NIH policy will be made where review by the proposed sIRB would be prohibited by a federal, tribal, or state law, regulation, or policy. Requests for exceptions that are not based on a legal, regulatory, or policy requirement will be considered if there is a compelling justification for the exception. The NIH will determine whether to grant an exception following an assessment of the need.
2. The Office for Human Research Protections expects that all sites located in the United States participating in cooperative research must rely upon approval by a single IRB for that portion of the research that is conducted in the United States. The reviewing IRB will be identified by the Federal department or agency supporting or conducting the research or proposed by the lead institution subject to the acceptance of the Federal department or agency supporting the research.
   
   

   The following research is not subject to this provision:

   1. Cooperative research for which more than single IRB review is required by law (including tribal law passed by the official governing body of an American Indian or Alaska Native tribe); or
   2. Research for which any Federal department or agency supporting or conducting the research determines and documents that the use of a single IRB is not appropriate for the particular context.
   3. For research not subject to paragraph (b) of this section, an institution participating in a cooperative project may enter into a joint review arrangement, rely on the review of another IRB, or make similar arrangements for avoiding duplication of effort.

1. Human Research involving personal data about individuals located in (but not necessarily citizens of) European Union member states, Norway, Iceland, Liechtenstein, and Switzerland is subject to EU General Data Protection Regulations.
2. For all prospective Human Research subject to EU GDPR, contact institutional legal counsel or your institution’s Data Protection Officer to ensure that the following elements of the research are consistent with institutional policies and interpretations of EU GDPR:
   1. Any applicable study design elements related to data security measures.
   2. Any applicable procedures related to the rights to access, rectification, and erasure of data.
   3. Procedures related to broad/unspecified future use consent for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens.
3. Where FDA or DHHS regulations apply in addition to EU GDPR regulations, ensure that procedures related to withdrawal from the research, as well as procedures for managing data and biospecimens associated with the research remain consistent with Appendices A-1 and A-2 above.

Investigators conducting human research should be aware of the following additional considerations associated with managing Human Research during an emergency/disaster scenario (e.g., extreme weather events, natural disasters, man-made disasters, infectious disease pandemics, etc.) related to investigators’ ongoing interactions with research subjects and the institutional review board (IRB) in such cases.

During Emergency/Disaster Scenarios: Deciding Whether a Study-Specific Risk Mitigation Plan for Ongoing Research Is Needed

In general, investigators should develop a study-specific emergency/disaster risk mitigation plan for their research unless one of the following is true:

• Research does not involve in-person interaction with research subjects.
• Research can be conducted as written while adhering to additional institution-level and HRPP-level guidance and requirements regarding the emergency/disaster event.
• The research is externally sponsored, and the sponsor has developed a protocol-specific risk mitigation plan for the research.
• The research has been voluntarily placed on hold for recruitment and all research procedures (except for necessary follow-up procedures to be done consistently with additional institution-level and HRPP-level guidance and requirements regarding the emergency/disaster event).

Tools and Resources for Developing Study-Specific Emergency/Disaster Risk Mitigation Plans for Ongoing Research

Review HRP–108—Flowchart—Study-Specific Emergency–Disaster Risk Mitigation Planning (DOCX)  and HRP–351—Worksheet—Protocol-Specific Emergency-Disaster Risk Mitigation Planning (DOCX) for general guidance on developing study-specific risk mitigation plans.

Voluntary Holds on Human Research Activities

Investigators may voluntarily elect to place all recruitment, enrollment and research procedures on temporary hold during emergency/disaster scenarios if doing so will better ensure the safety of research subjects and would not create any additional risks to the safety and welfare of research subjects. Such voluntary holds on research activity do not require IRB notification or review.

Submitting Study-Specific Emergency/Disaster Risk Mitigation Plans for IRB Review

If immediate modification of the research is necessary to eliminate an apparent immediate hazard to a subject, take action and notify the IRB within five business days following the standard pathway to submit reportable new information.

For all other study modifications made to ensure the ongoing safety of research subjects during emergency/disaster scenarios, submit a study amendment and all relevant new or modified study materials to the IRB.

Other Reportable New Information Considerations During Emergency/Disaster Scenarios

The IRB’s list of reportable events includes two items for which additional clarification and guidance may be helpful during emergency/disaster scenarios:

• “Failure to follow the protocol due to the action or inaction of the investigator or research staff.” Emphasis on action or inaction of the investigator or research staff has been added because this requirement does not include action or inaction of the research subject. For example, study teams may notice an increase in the number of subjects who do not arrive for scheduled research visits under emergency/disaster circumstances. Failure of a research participant to appear for a scheduled research visit is not noncompliance due to action or inaction by the investigator or research staff, and therefore does not require reporting to the IRB.
• “Change to the protocol taken without prior IRB review to eliminate an apparent immediate hazard to a subject.” During emergency/disaster scenarios, there will be cases where there is sufficient time to receive IRB approval of any proposed modifications to previously approved research, and in such cases, investigators should follow standard IRB procedures for submitting modifications. However, there will be other cases where investigators must make more immediate changes to the protocol or investigational plan to minimize or eliminate immediate hazards or to protect the life and well-being of research participants. Such changes may be implemented without IRB approval, but are required to be reported to the IRB within five business days afterward in accordance with IRB policies and procedures for submitting reportable new information.

• eConsenting Using REDCap—Modification Guide (DOCX)
• eConsenting Using REDCap—Start Guide (DOCX)