Investigator Manual

This document “INVESTIGATOR MANUAL” is designed to guide you through policies, procedures, and resources related to the conduct of human research that are specific to the University of Maryland, Baltimore. All human research-related activities must be in full compliance with current UMB HRPP and IRB policies and procedures while maintaining compliance with federal regulations and assuring the protection of human research participants.

General information regarding human research protections and relevant federal regulations and guidance is incorporated into the required human protections training. For additional information, see below: "What training do my staff and I need in order to conduct Human Research?”

Throughout this document, “organization” refers to the University of Maryland, Baltimore. Please refer to HRP-001 - SOP - Definitions for additional definitions.

This organization’s Human Research Protection Program (HRPP) is a comprehensive system to ensure the protection of the rights and welfare of participants in human research. The HRPP is based on all the individuals in this organization along with key individuals and committees fulfilling their roles and responsibilities described in this plan. Please refer to HRPP Plan

The UMB HRPP maintains a current Federalwide Assurance (FWA Update 12.20.2024) (UMB-signed assurance document) that obligates the institution to uphold ethical principles and is applicable whenever research is conducted or supported by any U.S. federal department or agency that has adopted the U.S. Federal Policy for the Protection of Human Subjects (also known as the Common Rule), unless exempt.

The UMB’s Institutional Review Board (IRB) functions independently, although in coordination with other organizational entities in its role in protecting human research participants. No organizational official or entity at any level can approve research that has not been reviewed and approved by an IRB. Refer to HRPP Plan

The Human Research Protections Office (HRPO) is the coordinating office for the HRPP and IRB. It is located within the Office of Academic Affairs-Research Compliance and reports to the Institutional Official. Refer to HRPP Plan

CICERO stands for Comprehensive, Institutional Collaborative Evaluation of Research Online.

The UMB HRPP maintains a web-based electronic system for creating, submitting, routing, signing, reviewing, and tracking research protocols. You can access CICERO via cicero.umaryland.edu

The document HRPP Plan defines the activities that this organization considers to be “human research” as defined in DHHS regulations at 45 CFR §46.102(d) and 45 CFR §46.102(f) and as defined in FDA regulations at 21 CFR §56.102(c), 21 CFR §56.102(e), and 21 CFR §812.3(p). An algorithm for determining whether an activity is human research can be found in the HRP-309 WORKSHEET - Human Research Determination (Educational Reference Only). Use this document for guidance as to whether an activity meets the DHHS or FDA definition of human research, keeping in mind that the IRB makes the ultimate determination in questionable cases as to whether an activity constitutes a human research subject to IRB oversight.

You are responsible not to conduct human research without prior IRB review and approval (or an IRB determination that the human research is Exempt). If you have questions about whether an activity is human research, request a determination from the Human Research Protections Office (HRPO) via CICERO. See below “How do I submit new Human Research to the IRB?” Also, see below “What are the different regulatory classifications that research activities may fall under?”

The document HRPP Plan describes this organization's overall plan to protect participants in human research:

• The mission of the Human Research Protection Program.
• The ethical principles that the organization follows governing the conduct of human research.
• The applicable laws that govern human research.
• When the organization becomes "engaged in human research" and when someone is acting as an agent of the organization conducting human research.
• The types of human research that may not be conducted.
• The roles and responsibilities of individuals within the organization

You are considered “engaged” in human participants’ research when you
1) Intervene or interact with living individuals for research purposes, or
2) Obtain individually identifiable private information for research purposes.

Further, a site is considered to be “engaged” in human participants’ research when it receives a direct federal award to support the research.

See HRP-310 - WORKSHEET - Engagement Determination

To qualify as a principal investigator, you must be a full-time (>51 percent effort) faculty member holding one of the following titles at UMB:

• Professor
• Associate professor
• Assistant professor

If you do not hold one of the above positions and wish to become a principal investigator, you must submit a written request with justification and your curriculum vitae for consideration by the Institutional Official. Contact:

Julie Doherty, RN, MSN
Director, Human Protections Administrator
620 W. Lexington St., 2nd Floor
Baltimore, MD 21201
Email: jdoherty@umaryland.edu
Phone: 410-706-3867

This request also must include a written agreement from a faculty member who meets the requirements of a principal investigator to mentor you on the conduct of human subject research. Students and fellows are not permitted to be principal investigators.

The IRB recognizes one principal investigator for each project. The principal investigator bears the ultimate responsibility for assuring that the conduct of the study complies with all UMB HRPP policies and procedures for the protection of human participants.

When the principal investigator for clinical studies involving medical/clinical interventions or investigational agents does not have a medical degree (MD), there must be at least one sub-investigator on the project that is a qualified MD with the appropriate expertise for the study.

All individuals involved in the design, conduct, and/or reporting of research must be adequately qualified and licensed relevant to the scope and complexity of the research conducted and their role in the research.

All individuals involved in the design, conduct, and/or reporting of research must be familiar with and know how to apply the ethical principles of The Belmont Report, current federal and state laws and regulations, current institutional policies and procedures, and Good Clinical Practice standards (see Appendix A ) when conducting research involving humans at UMB.

All individuals involved in the design, conduct, and/or reporting of research must complete the Collaborative Institutional Training Initiative (CITI) human participants online training program as well as HIPAA training. IRB approval will not be granted for proposed research in which the principal investigator has not completed the required human research protections training and HIPAA training listed below. The principal investigator of each research project is responsible for ensuring that all individuals involved in the design, conduct, and/or reporting of the research also have completed the required training.

The CITI site can be accessed at www.citiprogram.org. This training is valid for a three-year period, after which time a refresher CITI course must be completed. A minimum score of 80 percent overall must be obtained for CITI training. IRB approval for submissions will be withheld until all required training is verified.

All UMB employees are also required to complete HIPAA 125 training. In addition, individuals involved in the design, conduct, and/or reporting of research are required to complete HIPAA 201 training. Both of these trainings can be accessed at http://issomspweb.som.umaryland.edu/hipaa/quiz/index.asp.

Individuals that are external to the UMB system and are involved in the design, conduct, and/or reporting of research conducted at UMB must have completed their employer’s required certifications or trainings. External investigators must supply their CV and proof of the required certifications or trainings to the UMB principal investigator under which they are working. The UMB principal investigator will be responsible for forwarding these to the HRPO office when requested.

• Make sure that you have the adequate resources to protect the rights, welfare, and safety of human participants involved in the research, including:
  • Sufficient time to conduct, oversee, and complete research.
  • Adequate number of qualified staff.
  • A process to ensure that all persons involved in the design, conduct, and/or reporting of research are adequately informed about the protocol and their research-related duties and functions.
  • Adequate facilities in which to perform study procedures.
  • Availability of medical or psychological resources that participants may need as a consequence of the research.
  • Access to a population that will allow recruitment of the necessary number of participants.
• Make sure that the research application is consistent with the proposal for funding for extramural or intramural support.
• Act as a liaison between the IRB and the research sponsor (e.g., notification of IRB review and approval).
• Make sure there are additional protections for research involving vulnerable populations as required.
• If your research involves entities within UMB that are not under your control, you must ensure appropriate communication, education, and training of those staff.
• Refer to the Center for Clinical Trials and Corporate Contracts (CCT) website for information regarding correct research billing procedures: Clinical Trials and Corporate Contracts
• If your research is sponsored by a commercial sponsor, please refer to the Corporate Contracts section of the CCT website: Clinical Trials and Corporate Contracts
• If your research is sponsored by a federal agency, foundation, or other nonprofit organization, please see Sponsored Program Administration section on the Research @ UMB website: Sponsored Programs Administration 
• If your research involves investigational drugs, biologics, or devices, you must follow HRP-092 SOP: Control of Investigational Test Articles.

Your research may be regulated by more than one federal agency, depending on the project funding and type of project. Regardless of funding source, all human participant research must meet the regulatory criteria for approval. See HRP-311 - WORKSHEET - Criteria for Approval and Additional Considerations.

• If your research is funded by a federal agency, you are required to follow Department of Health and Human Services (DHHS) regulations at 45 CFR 46. Also refer to Appendix A for more information.
• If your research involves drugs or devices, you are required to follow Food and Drug Administration (FDA) regulations at 21 CFR 50 and 21 CFR 56. Also refer to Appendix A for more information.
• If your research involves the use of a drug with an active Investigational New Drug (IND) application, you are required to follow FDA regulations at 21 CFR 312. Also refer to Appendix A for more information.
  • If you are the IND holder, you are required to follow both the investigator responsibilities and sponsor responsibilities at 21 CFR 11, 21 CFR 54, 21 CFR 210, 21 CFR 312, 21 CFR 314, 21 CFR 320, 21 CFR 330, and 21 CFR 601.
• If your research involves the use of a device with an active Investigational Device Exception (IDE), you are required to follow FDA regulations at 21 CFR 812. Also refer to Appendix A for more information.
  • If you are the IDE holder, you are required to follow both the investigator responsibilities and sponsor responsibilities at 21 CFR 11, 21 CFR 54, 21 CFR 812, 21 CFR 814, 21 CFR 820, and 21 CFR 860.
• If your research involves the use of veterans, Veterans Health Administration (VHA) funding or other VA resources, you are required to follow regulations in VHA Handbook 1200.05. Also refer to Appendix A for more information.
• If your research involves funding by a federal agency other than DHHS and NIH, you are required to follow regulations pertaining to those agencies:
  • Department of Defense: See Appendix A
  • Department of Energy: See Appendix A
  • Department of Education: See Appendix A

Yes, the IRB charges to review certain research proposals for Industry-Supported Applications.

Contact the Center for Clinical Trails and Corporate Contracts office for further information.

Complete a CICERO application, attach all required documents, and submit to the HRPO. If you are unsure if the project is human participants research, refer to HRP-309 WORKSHEET - Human Research Determination (Educational Reference Only) 

** All research proposals require a CICERO application.

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

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 10b) or has a separate waiver request included with FDA 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:

1. • A thorough patient history and treatment plan, included in the Form 3926 or in a separate document that includes: proposed daily dose, route, and frequency of administration planned treatment; criteria for discontinuation of treatment; 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 to the patient if appropriate.
   • The key details of the patient’s history, including diagnosis and summary of prior therapy (including response to such therapy); the reason for the request , including an explanation of why the patient lacks other therapeutic options ; and information regarding a patient’s relevant clinical characteristics (such as comorbid conditions and concomitant medications) that is necessary to assess the potential risks of the drug; and
   • A summary of known risks of the drug

Use UMB Consent Template to prepare your consent document. A continuing review application must be submitted to the IRB at least annually, and any modifications or new new information should be reported accordingly.

2. Compassionate Use (Individual patient/small group access) of a device Request for compassionate use of a device should be submitted to the IRB as a new study. See HRP 325 Worksheet – Device Compassionate Use for the regulatory criteria allowing such a use  and make sure they are followed. The FDA does not consider the compassionate of an unapproved device to be a clinical investigation, however it is expected that informed consent be obtained. Use UMB Consent template to create 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 srug
5. Treatment use of a device

Request for any of these three 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 Brochure, device/product manual, patient-facing materials, etc…)/ Use UMB Consent template. A continuing review application must be submitted at least annually, and any other  modifications or new information should be submitted accordingly.

Although the clinical use of a HUD is not considered research, the FDA requires that it is submitted for review and approval by the IRB prior to use (with the exception of emergency use).  The UMB utilizes the UMB IRB to review and approve the use of a HUD before it can be used at a facility for clinical care.

Please refer to HRP-314 - WORKSHEET - Criteria for Approval & Additional Considerations HUD for additional information regarding the criteria that the IRB uses to review and approve HUD uses.  

The use of the UMB IRB informed consent template is not required by the IRB for HUD use. However, the IRB may request the use of the informed consent document if it is determined to be in the best interest of the patient.

• Abbreviated Title: Enter the abbreviated title. This is the title that will appear in the CICERO application.
• Full Title: Enter the full protocol name. This title will be entered into the determination letter.
• Select Type of Submission: Select the appropriate type of submission.
• Application: Select whether or not you have an existing research protocol. This can be a sponsor’s protocol or other type of protocol that has all of the required information. See below “How do I write an Investigator Protocol?”

Complete the remaining sections in the application as appropriate. Remember that if you have an existing protocol, you can reference sections or page numbers of that protocol in the CICERO application. Read all of the instructions for each section. Provide all the information requested, as appropriate for the research protocol.

Research Team

• Principal Investigator: Name the person with overall responsibility for the conduct of the human research. There can only be one investigator with this overall responsibility. If you are not listed on the principal investigator drop-down list, see above section “Can I be a principal investigator for a study?” to determine if you meet the criteria for principal investigator privileges. If you meet the criteria, please contact HRPO at 410-706-5037 or email hrpo@umaryland.edu for assistance.
• Point of Contact: Who is the alternative point of contact for the principal investigator. This person can be a study coordinator or any other study team member. In case the IRB cannot contact the principal investigator, this person is a secondary person to contact. A person listed as Point of Contact (POC) cannot also be listed under “Other Team Members.”
• Other Team Members: List all human research personnel involved in the design, conduct, or reporting of the human research and their roles. This includes all co-investigators, subinvestigators, coordinators, assistants, students, and collaborators who have a role in the design, conduct, or reporting of the human research.

When adding each person, you must select whether or not to give “edit rights.” Selecting “yes” will allow the person to edit the online forms and to execute activities (protocol modifications, reportable events, etc.) in CICERO. Note: Granting a person edit rights will automatically add them to the email CC list and this person will receive all emails from CICERO to the team regarding the submission. In addition, for each person added, you must select whether or not they will receive emails sent to the principal investigator by CICERO and the HRPO.

Each person who is added to the protocol must complete a Conflict of Interest statement. CICERO will send each person an email. Individuals must update their Conflict of Interest statement within 10 days of the becoming aware of any change in a financial interest that affects this statement. The principal investigator is responsible for ensuring that all investigators and research staff comply with this requirement. When there are questions about the qualifications of research team members, the Organizational Official can be consulted and make determinations about further actions.

Approvals Required Prior to Initiating Research

Check all additional approvals that are required:

• Radiation being used for reasons other than clinical care
• The use of any biohazards
• Research involving human gene transfer or immune response
• Research involving cancer
• Research using VA patients, facilities, or personnel

Department Scientific and Feasibility Review

All new research submissions must undergo Department Scientific and Feasibility Review. If your research involves a department other than your department, a specialty review also must be completed. For example, if your research involves children (review required from the Department of Pediatrics) or cancer (review required from the Greenebaum Cancer Center), CICERO will send reviews to these departments automatically when you submit the application. When the department chair is the principal investigator, the Department Scientific and Feasibility Review must be completed by an individual outside of the PI's department.

All research submissions must have a completed application form in CICERO or a separate research protocol attached and referenced in CICERO. Follow the application instructions in CICERO. If you have a sponsor’s protocol, you may reference pages in the sponsor’s protocol in the corresponding sections of the CICERO application. Here are some key points to remember when completing the CICERO application or creating your own separate research protocol document:

• For an Investigator Protocol document:
  • The italicized bullet points in the templates serve as a guide to investigators when developing an Investigator Protocol for submission to the IRB. All italicized comments are meant to be deleted prior to submission.
  • Note that, depending on the nature of your research, certain sections of the template may not be applicable to your Investigator Protocol. Skip these sections as appropriate.
• You may not involve any individuals who are members of the following populations as participants in your research unless you indicate this in your inclusion criteria as the inclusion of participants in these populations requires additional protections. Students and employees may be enrolled like any other vulnerable population. CICERO will provide additional information and requirements for these vulnerable populations:
  • Adults unable to consent
  • Individuals who are not yet adults (infants, children, teenagers)
  • Pregnant women
  • Prisoners
  • Employees
  • Students

Use the Consent Form Templates to create a consent document. Note that all consent documents must contain all of the required and all additional appropriate elements of informed consent disclosure. Review Section 7 of the HRP-311 - WORKSHEET - Criteria for Approval and Additional Considerations to ensure that these elements are addressed. For research involving the VA, you must use a VA consent form, VA 10-1086.

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 the IRB’s HRP-311 - WORKSHEET - Criteria for Approval and Additional Considerations to ensure that these elements are addressed. When using the short form of consent documentation, the appropriate signature block from “TEMPLATE CONSENT DOCUMENT” should be used on the short form.

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

Participants who do not speak English should be presented with informed consent documents in a language understandable to them that includes all the required and additional elements for disclosure. Either the long form of the consent document needs to be translated in writing into the subject’s language or the short form of consent document may be used. With the short form of consent documentation, the long form of consent may be translated orally and only a small portion of the information translated into the subject’s language.

Please see below “How do I document consent?” and the requirement for the short-form consent on HRP-318 - WORKSHEET - Short Form of Consent Documentation

Ensuring Appropriate Telephone Contact with Subjects. This pertains to contacting the subject by telephone. Research team members are prohibited from requesting Social Security numbers by telephone.

• Initial contact: During the recruitment process, ensure that the research team makes initial contact with the potential subject in person or by letter prior to initiating any telephone contact, unless there is written documentation that the subject is willing to be contacted by telephone about the study in question or a specific kind of research (e.g., if the potential subject has diabetes, the subject may indicate a desire to be notified of any diabetes-related research studies) or the IRB has determined otherwise, with appropriate justification.NOTE: One source of information about clinical trials that can be shared with potential subjects is the NIH clinical trials website (http://www.clinicaltrials.gov) where clinical trials are listed.
• Later contact: Ensure that the research team begins telephone calls to the subject by referring to previous contacts and, when applicable, the information provided in the informed consent form, and ensure that the scope of telephone contacts with the subject is limited to topics outlined in IRB-approved protocols and informed consent forms.

The IRB may approve a consent procedure that does not include, or that alters, some or all of the required elements of informed consent. Refer to HRP-415 - CICERO CHECKLIST - Waiver or Alteration of the Consent Process. Also, the IRB may approve a consent procedure that waives the requirements to obtain written informed consent entirely. Refer to HRP-416 - CICERO CHECKLIST - Waiver of Written Documentation of the Consent Proc.

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 of the subject’s legally authorized perspective, 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 (LAR), 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. See below for further guidance regarding the requirement to obtain HIPAA authorization or waiver of HIPAA authorization for recruitment purposes.

The Health Insurance Portability and Accountability Act (HIPAA) regulates how protected health information can be used and disclosed. An investigator must obtain an authorization via a HIPAA authorization form from all participants in research before the use or disclosure of protected health information (PHI) for any research-related purpose. PHI is any information in the medical record or designated record set that can be used to identify an individual. In addition, refer to HRP-331 - WORKSHEET - HIPAA Authorizations for Research for elements required in a HIPAA authorization form.

The IRB can waive or alter the requirement for HIPAA authorization for study recruitment purposes or for the entire study. Refer to HRP-441 - CICERO CHECKLIST - HIPAA Waiver of Authorization

Certain research projects are required to register at the website ClinicalTrials.gov. These projects also are responsible to update records and report results per policy. Refer to HRP-095 - SOP Clinical Trials and ClinicalTrials.gov Instructions for the Research Community.

Submitted activities may fall under one of the following four regulatory classifications:

• Not Human Research: Activities must meet the DHHS or FDA definition of “research” involving “human participants” for the activity to fall under IRB oversight. Activities that meet neither definition of “Research” involving “Human Participants” are not subject to IRB oversight or review. Refer to HRP-309 WORKSHEET - Human Research Determination (Educational Reference Only). Contact the Human Research Protections Office (HRPO) in cases in which it is unclear whether an activity meets the regulatory definition of Human Research. When a project is determined to be nonhuman subject research, that determination is made by the particular information provided in the CICERO application. If you make any changes to the project, you must submit a protocol modification to determine if the project remains nonhuman participant research.
• Exempt: Certain categories of human research may be exempt from regulation but require IRB review. It is the responsibility of the IRB, not the investigator, to determine whether human research is exempt from IRB review. Refer to HRP-401 - CICERO CHECKLIST - Pre-Review and Administrative Review for reference on the categories of research that may be exempt. When a research study is determined to be exempt, that determination is made on the particular information provided in the CICERO application.
  Exemption #7: Storage/Maintenance of Identifiable Biospecimens with Broad Consent and Exemption #8 Use of Identifiable Data/Biospecimens Obtained with Broad Consent are currently not being implemented at UMB.
  * If you make any changes to an exempt study, you must submit a protocol modification to determine if the research study continues to meet the exemption status.
• Review Using the Expedited Procedure: Certain categories of nonexempt Human Research may qualify for review using the expedited procedure. Refer to HRP-401 - CICERO CHECKLIST - Pre-Review and Administrative Review for reference on the categories of research that may be reviewed using the expedited procedure.
• Review by the Convened IRB: Non-Exempt Human Research that does not qualify for review using the expedited procedure must be reviewed by the convened IRB.

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 section below “How does the IRB decide whether to approve Human Research?”
• Modifications Required to Secure Approval: Made when the IRB requires specific modifications to the research before approval can be finalized. See section below “What will happen after IRB review?”
• Deferred: Made when the IRB determines that it is unable to approve research and the IRB has recommendations that might make the protocol approvable. When this motion is made, the IRB describes its reasons and recommendations. See section below “What will happen after IRB review?”
• 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 this motion is made, the IRB describes its reasons. See section below “What will happen after IRB review?”
• Tabled: Made when the IRB cannot approve the research at a meeting for reasons unrelated to the research, such as loss of quorum. These are often administrative reasons. When taking this action, the IRB automatically schedules the research for review at a future meeting.

The criteria for IRB approval can be found in HRP-311 - WORKSHEET - Criteria for Approval and Additional Considerations for non-exempt human research. The latter worksheet references other checklists that might be relevant. All checklists and worksheets can be found on the HRPO website.

These checklists and worksheets are used for initial review, continuing review, and review of modifications to previously approved human research.

YOU ARE ENCOURAGED TO USE THE CHECKLISTS AND WORKSHEETS TO WRITE YOUR INVESTIGATOR PROTOCOL IN A WAY THAT ADDRESSES THE CRITERIA FOR APPROVAL.

The IRB will provide you with a written determination indicating that the IRB has approved the human research, requires modifications to secure approval, or has deferred, tabled, or disapproved the human research.

The IRB can approve a research project for no more than 365 days. Federal regulations make no provision for any grace period extending the conduct of research beyond the expiration date of IRB approval; therefore, continuing review and reapproval of research must occur before the date when IRB approval expires. If this does not happen, all research activities must cease. See section below “What do I do if my study expires?”

• If the IRB has approved the human research: The human research may commence once all other organizational approvals have been met. IRB approval is good for a limited period of time, which is noted in the approval letter.
• If the IRB requires modifications to secure approval and you accept the modifications: Make the requested modifications and submit them to the IRB as soon as possible via CICERO. 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 respond to the IRB within 30 days, the offer of approval with the requested modifications will be withdrawn. If you do not accept the modifications, write up your response and submit it to the IRB within 30 days. If you do not provided additional information or correspondence within 30 days, and the IRB will require a completely new submission.
• If the IRB defers the human research: The IRB will provide a statement of the reasons for deferral and any recommendations that might make the protocol approvable. Make the recommended changes and respond to each of the IRB’s questions/concerns and submit them to the IRB as soon as possible via CICERO. Once a complete response has been received, the submission will be scheduled for review at an IRB meeting.
• If the IRB disapproves the human research: The IRB will provide a statement of the reasons for disapproval. If the investigator wishes to pursue the research project, a new CICERO application must be submitted.

In all cases, you have the right to address your concerns to the IRB directly at an IRB meeting. To request this, contact the Director, Regulatory Compliance. You may address the IRB panel via teleconference.

Depending on the type of research you do, where it is done, what procedures are involved, and other factors, your research proposal may need to be reviewed by a committee in addition to the IRB. Some of these required approvals will be captured by your CICERO application.

For VA research, the investigators must submit the appropriate documentation to the VA R&D Committee for initial review and approval. Investigators also must submit modification documentation to the VA R&D committee for review and approval for any modifications related to biosafety or radiation safety.

• Do not start human research activities until you have the final IRB approval letter (including washout and screening).
• Do not start human research activities until you have the approval of departments or divisions that require approval prior to commencing research that involves their resources. CICERO will automatically send notification to the required departments from the questions you answer within your CICERO application. You will be able to see the department’s responses in CICERO’s history log for your study.
• Do not start human research activities until organizational approvals are met. See "Approvals Required Prior to Initiating Research."
• Personally conduct or supervise the human research.
  • Protect the rights, safety, and welfare of participants involved in the research.
  • 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.
  • Assure that each participant is adequately informed and freely consents to participate in the research, unless a waiver of consent has been obtained from the UMB IRB. The principal investigator must personally assure that every reasonable precaution is taken to reduce risks to participants.
  • Delegate responsibility to the research staff in accordance with the staff’s training and qualifications.
  • Assure that all procedures associated with the research are performed, with the appropriate level of supervision, only by individuals who are licensed or otherwise qualified to perform them under the laws of Maryland and polices of the University of Maryland, Baltimore.
  • Monitor the research study and perform quality management activities to ensure the protection of participants and the quality of the research data. Deficiencies identified during quality improvement processes must be addressed in a timely manner. Refer to “CHECKLIST: Investigator Quality Improvement Assessment” for more information.
  • Do not modify the human research without prior IRB review and approval unless necessary to eliminate apparent immediate hazards to participants.
  • Changes in approved research that are initiated without IRB approval to eliminate apparent immediate hazards to the participant are promptly (within five days) reported to the IRB and are reviewed by the IRB to determine whether each change was consistent with ensuring the participants’ continued welfare.

Changes in approved research that are initiated without IRB approval to eliminate apparent immediate hazards to the participant are promptly (within five days) reported to the IRB and are reviewed by the IRB to determine whether each change was consistent with ensuring the participants’ continued welfare.

• Submit to the IRB:
  • Proposed modifications as described in this manual. See below “How do I submit a modification?”
  • A continuing review application no later than SIX WEEKS PRIOR to the expiration date found in the IRB approval letter for your study. See below “How do I submit a continuing review?”
  • A closure report when the human research is closed. See below “How Do I Close Out a Study?”
• Do not accept or provide payments to professionals in exchange for referrals of potential participants (“finder’s fees.”)
• Do not accept payments designed to accelerate recruitment that were tied to the rate or timing of enrollment (“bonus payments.”)
• Be open to participants’ complaints or requests for information. Investigators and research staff should follow a process to respond appropriately to such complaints.
  • Notify the IRB of any participant's or other individual’s complaints regarding the research. The complaint may be reported at continuing review if it involves no risk to the participants or others or does not change the risk/benefit analysis (e.g., a participant complains that they do not like the investigator’s clinic hours and subsequently withdraws from the research).
  • Report complaints that involve potential risks to participants or others or result in a possible change in the risk/benefit analysis as an unanticipated problem as soon as possible, but no later than FIVE WORKING DAYS after the investigator first learns of the complaint (e.g., a member of the research team where the research is conducted complains that the research assistant has not maintained her research notes in a confidential manner, which may have potentially breached confidentiality).
• See additional requirements of various federal agencies in Appendix A.

In order to help facilitate human research and to avoid duplicative IRB review while at the same time protecting the rights and welfare of human subjects, the University of Maryland Baltimore is willing to rely on external IRBs The UMB has negotiated master reliance agreements with the following external IRBs that may be applicable when UMB researchers are involved in certain clinical trials. Central Institutional Review Board (CIRB) of the National Cancer Institute (NCI) for the review of adult and pediatric national multi-centered cooperative oncology group cancer treatment trials.

The UMB has entered into IRB authorization agreements, reviewed on a case-by-case basis, with many IRBs for both NIH and federally-funded, multi-center, collaborative protocols. The Vice President & Chief Accountability Officer in their role as Institutional Official is vested with the authority to make the decision whether or not to rely on another IRB.

UMB is also a member of Smart IRB, a platform designed to ease common challenges associated with initiating multisite research and to provide a roadmap for institutions to implement the NIH Single IRB Review policy (effective date: January 25, 2018). Freely available for institutions and investigators, SMART IRB is an integrated, comprehensive platform that allows flexibility in the size and scope of collaboration to enable IRB reliance for multisite studies across the nation, regardless of funding status.

• Complete the IRB application in CICERO and indicate that an External IRB will serve as the IRB of Record.
• Provide all requested information and documents, including the completed required reliance document, as applicable.
• Submit the application, which then goes through Departmental Review.
• When all processes and approvals related to the reliance are fully executed, the state in CICERO will change to 'External IRB.'
• Questions related to reliance on external IRBs and reliance agreements can be addressed to Scott Evans, UMB IRB Analyst sevans@umaryland.edu or Dr. Julie Doherty at jdoherty@umaryland.edu.

• Obtain appropriate approvals from this institution prior to seeking review by another IRB.
• Comply with determinations and requirements of the reviewing IRB.
• 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.
• Notifying the reviewing IRB when local policies that impact IRB review are updated.
• Cooperating 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.
• Disclosing conflicts of interest as required by the reviewing IRB and complying with management plans that may result.
• Promptly reporting 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.
• When enrolling participants, obtain, document and maintain records of consent for each participant or each participant's legally authorized representative.
• Promptly reporting to the reviewing IRB any unanticipated problems involving risks to participants or others according to the requirements specified in the reliance agreement.
• Providing the reviewing IRB with data safety monitoring reports in accordance with the reviewing IRB’s reporting policy.
• Reporting non-compliance, participant complaints, protocol deviations or other events according to the requirements specified in the reliance agreement.
• Specifying 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.
• Reporting external IRB determinations of serious non-compliance, continuing non-compliance, serious and continuing non-compliance and unanticipated problems involving risk to research subjects or others through CICERO for institutional review and consideration.

• Coordinating 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.
• Identifying all sites that will be engaged in the human research and requiring oversight by the IRB.
• 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.
• 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.
• Respond to questions or information requests from study teams or the IRB or HRPP staff at relying sites.
• Provide relying site investigators with the policies of the reviewing IRB.
• Provide relying site investigators with the IRB-approved versions of all study documents.
• Preparation and submission of IRB applications on behalf of all sites. This includes initial review, modifications, personnel updates, reportable new information and continuing review information for all sites.
• Establishing 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.
• Ensuing that consent forms used by relying sites follow the consent template approved by the reviewing IRB and include required language as specified by the relying sites.
• Providing site investigators with all determinations and communications from the reviewing IRB.
• Submitting reportable new information from relying sites to the reviewing IRB in accordance with the terms outlined in the authorization agreement or communication plan.
• Reporting the absence of continuing review information from relying sites if they do not provide the required information prior to submission of the continuing review materials to the reviewing IRB. Notifying the relying site of their lapse in approval and applicable corrective actions.
• Providing study records to the relying institution, reviewing IRB or regulatory agencies upon request.

Consent to participation in research is documented by the use of an informed consent document that has been signed by the participant or the participant’s legally authorized representative. Use the signature block approved by the IRB. Complete all items in the signature block. Refer to HRP-090 SOP: Informed Consent Process for Research and HRP-091 SOP: Written Documentation of Consent

The following are the requirements for long-form consent documents:

• The subject or representative signs and dates the consent document.
• The individual obtaining consent signs and dates the consent document.
• Whenever required by the IRB the subject’s or representative’s signature is to be witnessed by an individual who signs and dates the consent document.
• For participants who cannot read and whenever required by the IRB or the sponsor, a witness to the oral presentation signs and dates the consent document.
• A copy of the signed and dated consent document is to be provided to the subject.
• For Veterans Affairs (VA) research, consent must be documented on a Veterans Affairs (VA) Form 10-1086.

The following are the requirements for short-form consent documents:

• The subject or representative signs and dates the consent document.
• The individual obtaining consent signs and dates the summary.
• The witness to the oral presentation signs and dates the consent document and the summary. The person obtaining consent may not be the witness to the consent.
• A copy of the signed and dated consent document and a copy of the signed and dated summary are to be provided to the person signing the document.
• For Veterans Affairs (VA) research, consent must be documented on a Veterans Affairs (VA) Form 10-1086.

Certain information must be reported to the IRB in a prompt manner, within FIVE business days of the investigator becoming aware of the information. See Study Conduct section “REPORTABLE NEW INFORMATION BULLETIN” for a list of information that is requires prompt reporting.

All other events can be reported to the IRB in an aggregate fashion at the time of continuing review.

Complete the “Create Modification” application in CICERO. Attach relevant documents and submit. Please note that research must continue to be conducted without inclusion of the modification until IRB approval is received.

The IRB must determine if any criteria for approval are affected by the modification and, if so, that the particular criterion continues to be met. See HRP-311 - WORKSHEET - Criteria for Approval and Additional Considerations For additional information, refer to HRP-021 - SOP - Pre-review and HRP-401 - CICERO CHECKLIST - Pre-Review and Administrative Review.

Complete the “Create Continuing Review” application in CICERO. Attach relevant documents including any data safety monitoring committee review, and submit. A Continuing Review application must be submitted at least SIX WEEKS PRIOR TO THE EXPIRATION DATE of the IRB approval indicated in the approval letter.

During continuing review the IRB must determine if the criteria for approval continues to be met. See HRP-311 - WORKSHEET - Criteria for Approval and Additional Considerations For additional information, refer to HRP-021 - SOP - Pre-review and HRP-401 - CICERO CHECKLIST - Pre-Review and Administrative Review

If the IRB approval for your study expires, all human research procedures related to the protocol under review must cease, including recruitment, advertisement, screening, enrollment, consenting, interventions, interactions, and collection of research data. In addition, any data analyses of previously collected research data must cease. Continuing human research procedures without IRB approval is a violation of federal regulations.

If current participants 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 participants. If current participants will be harmed by stopping human research procedures that are not available outside the human research context, immediately contact the IRB chair for guidance. Remember that research data cannot be collected during study expiration.

To be eligible for closure, the IRB study must meet all of the following criteria:

• Data collection is complete.
• There is no more participant contact, including phone calls, long-term follow-up, data collection visits, and surveys.
• The only research activity being conducted is data analysis of de-identified data.

Complete the “Closure Report” in CICERO. Attach relevant documents and submit the report. A Closure Report must be submitted within 45 days of study closure. If you fail to submit a Closure Report to close out human research, you will be restricted from submitting new human research until the completed application has been received.

If the Closure Report for closing out a human research study is not received by the date requested in the approval letter, you will be restricted from submitting new human research until the completed application is received.

If your IRB approval lapses for any reason, your new research applications will not be reviewed by the IRB. Also, if you fail to submit a protocol continuing review by the date requested on the approval letter or you fail to submit a protocol closure report within 45 days of the end of the study, your new research applications will not be reviewed by the IRB. You will know you are on the restricted list if your name appears in red on any of your research protocols in CICERO.

Once you have submitted the outstanding continuing review or protocol closure report, your name will be taken off the restricted list.

Maintain your human research records, including signed and dated consent documents, for at least THREE YEARS after completion of the research. Maintain signed and dated HIPAA authorizations and consent documents that include HIPAA authorizations for at least SIX YEARS after completion of the research.

If your human research is sponsored, contact the sponsor before disposing of human research records.

If your research is regulated by the FDA, refer to Appendix A for specific research record retention guidelines.

If your research involves the VA, refer to Appendix A for specific research record retention guidelines.

If you are planning to move to another location and leave UMB, the IRB must be notified. You can have another UMB investigator assume principal investigator responsibilities, you can close each of your research studies with the IRB, or you can transfer the research studies to the new location.

You also must notify the IRB in writing of the plan for destroying the data or transferring the data to another principal investigator. The original research study documents are the property of UMB and must remain at UMB.

Contact the Human Research Protections Office (HRPO) or IRB chair immediately to discuss the situation. If there is no time to make this contact, see the HRP-317 - WORKSHEET - Emergency Use of a Test Article for the regulatory criteria allowing such a use and make sure these criteria are followed. You will need to submit a report of the use to the IRB WITHIN FIVE DAYS of the use and an IRB application for initial review WITHIN 30 DAYS.

If you fail to submit the report within five days or the IRB application for initial review within 30 days, you will be restricted from submitting new human research until the report and IRB application for initial review have been received. For additional information, see HRP-023 SOP: Emergency Use of a Test Article Review

Emergency use of an unapproved drug or biologic in a life-threatening situation without prior IRB review is “research” as defined by FDA, the individual getting the test article is a “subject” as defined by FDA, and therefore is governed by FDA regulations for IRB review and informed consent. Emergency use of an unapproved device in a life-threatening situation without prior IRB review is not “research” as defined by FDA and the individual getting the test article is not a “subject” as defined by FDA. However, FDA guidance recommends following similar rules as for emergency use of an unapproved drug or biologic.

Individuals getting an unapproved drug or device in a life-threatening situation 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.

Please see HRP-415 - CICERO CHECKLIST - Waiver or Alteration of the Consent Process for the criteria that IRB needs to determine are met to approve the conduct of such research.

This document and the policies and procedures for the Human Research Protection Program are available on the HRP website.

If you have any questions or concerns about the Human Research Protection Program, contact the Human Research Protections Office (HRPO) at:

Human Research Protections Office
620 W. Lexington St., 2nd Floor
Baltimore, MD 21201
hrpo@umaryland.edu
(410) 706-5037

If you have questions, concerns, complaints, allegations of undue influence, allegations or findings of non-compliance, or input regarding the Human Research Protection Program that cannot be addressed by contacting the Human Research Protections Office (HRPO), follow the directions in the “HUMAN RESEARCH PROTECTION PROGRAM PLAN” under “Reporting and Management of Concerns.”

Appendix A-1 — Additional Requirements for DHHS-Regulated Research

Appendix A-2 — Additional Requirements for FDA-Regulated Research

Appendix A-3 — Additional Requirements for Clinical Trials (ICHGCP)

Appendix A-4 — Additional Requirements for Department of Defense (DOD) Research

Appendix A-4 — Additional Requirements for Department of Navy (DON) Research

Appendix A-5 — Additional Requirements for Department of Energy (DOE) Research

Appendix A-6 — Additional Requirements for Department of Education (ED) Research

Appendix A-7 — Additional Requirements for Veterans Administration (VA) Research

Appendix A-8 — Additional Requirements for the Department of Justice (DOJ) Research

Additional Requirements for DOJ Research Conducted Federal Bureau of Prisons

Additional Requirements for DOJ Research Funded by the National Institute of Justice

Appendix A-9 — Additional Requirements for Environmental Protection Agency (EPA)

Appendix A-10 — sIRB Studies—Federally Funded

Appendix A-11 — sIRB Studies—NIH funded

Appendix A-12 — Additional Requirements for Research Subject to General Data Protection Regulations (GDPR)