Clinical and Translational Science Institute
Advancing today’s discoveries to improve health for all.

Independent Safety Monitor

Independent Safety Monitor

The CTSI can provide assistance with clinical research monitoring on investigator-initiated trials.

Independent Safety Medical Monitor Support we provide:

  • Physician Advisor to the protocol team/sponsor investigator on Safety Oversight for low risk Investigator Initiated Trials
  • Independent real-time safety monitoring through reviewing adverse events (including Serious Adverse Events) and safety reports
  • Independent Adverse Event assessment/attributions
  • Evaluation of individual and cumulative study data to make recommendations regarding the safe continuation of the study.
  • Detailed review of study related documents

An independent safety monitor’s primary responsibility is to provide independent safety monitoring in a timely fashion, by reviewing adverse event and serious adverse event details in real time, from discovery to event resolution. They will make recommendations and act as in an advisory role to the sponsor-investigator for investigator-initiated trials.

Request support for Independent Safety Monitoring

FAQs

Study Monitoring

Study Monitoring

The CTSI can provide assistance with clinical research monitoring on investigator-initiated trials. 

This is a service under the CTSI Trial-CORE. These services are available to staff at both Ohio State and Nationwide Children's Hospital. At Nationwide Children's Hospital the CRC provides study monitoring services.

  • Templates and Guidance- If you have a research team we can provide Study Monitoring templates, monitoring plans and guidance on how to ensure you have a strong data quality assessment.
  • Staffing of Study Monitoring- An independent experienced staff member can be budgeted to provide regulatory oversight and source data verification paying special attention to the following items:
    • Adverse Events
    • Protocol Deviations
    • Protocol specified Outcome Measures
    • Regulatory Document Review
    • Training Documentation
    • Consent Process Documentations
    • Inclusion/Exclusion Criteria Review

 

To learn more or request a consultation, email CTSI-info@osumc.edu.

Data Safety Monitoring Board (DSMB)

Data Safety Monitoring Board (DSMB)

Everything you need to know to create a DSMB.

DSMB Support we provide: 

  • Letter of Support (LOS) for grant applications, upon request
  • Detailed review of study related documents 
  • Intake meeting with Principal Investigator (PI), DSMB Chair and DSMB program manager
  • Initial DSMB meeting with study team, DSMB members and NIH representatives, if applicable
  • Data and safety review meetings with study team, DSMB members and NIH representatives, if applicable
  • Executive meetings with PI and DSMB Chair
  • Ad hoc/prompt reviews for safety events
  • Study Terminations 

Request support for DSMB by contacting the CTSI Regulatory Knowledge and Support.

The CTSI DSMB is a group composed of a DSMB Program Chair, a DSMB program manager, a biostatistician and two to three experts in the field of research being studied. Optional DSMB members may include a clinical trial methodology expert, patient advocate and a/or bioethicist. Voting DSMB members must be free of any significant financial, scientific and academic conflict of interest with the study and study PI.  

FAQs

Essential Documents

Essential Documents

Find essential documents that are used to evaluate the conduct and quality of clinical trials.

Essential Document Support we provide: 

  • Essential Document Templates
  • Essential Document Consultations

Request support for Essential Documents by contacting the CTSI-Regulatory Team. 

What are Essential Documents?

Required study related documents that are used to evaluate the conduct of a clinical trial and the quality of the data produced. These documents serve to:

  • Demonstrate the compliance of an investigator, sponsor and monitor with the standards of Good Clinical Practice (GCP) and applicable regulatory requirements
  • Assist with the successful management of the trial by the investigator, sponsor and monitor
  • Used for auditing/inspecting by the sponsor’s auditor or regulatory inspector(s)

The term essential document is defined by the International Council for Harmonization Good Clinical Practice E6 A2 (ICH-GCP E6A2) (PDF) and a detailed list of required essential documents can be found in section eight of that guideline.  

Essential documents are commonly referred to as regulatory documents. Regulatory documents may also include predicate documents, which are documents required to be maintained by Title 21 Code of Federal Regulations (21 CFR) and that the FDA requires a company to submit to them as part of compliance for FDA regulated research.

What Kind of Media should be Used for Essential Documents?

Essential documents may be electronic or paper.  Some essential documents, such as source documents, may be stored as audio tapes, recordings or images.  

If conducting FDA regulated human subject’s electronic essential documents should comply with 21 CFR Part 11: Electronic Records; Electronic Signatures and  Part 11, Electronic Records; Electronic Signatures – Scope and Application.   

Established electronic systems used for some or all essential documents by Ohio State Researchers include:

  • REDCap
  • Advarra eReg – currently available for CCC and COM
  • Advarra EDC – currently available for CCC and COM
  • DocuSign
  • Qualtrix
  • IHIS

Where should Essential Documents be Stored?

Essential documents should be stored in an electronic or paper-based site master file. The site master file should be established at the beginning of the research study and maintained throughout the study. Unless otherwise noted, essential documents should also be filed with the study sponsor or Contract Research Organization (CRO) in their trial master file.

Records regarding the location of the essential documents should be maintained by the sponsor and the investigator/institution. Additionally, identification of the storage system(s) used during the trial and archival process should include information related to document identification, version history and the search and retrieval process.

If conducting an Investigator Initiated Multi-Center Trial, the Sponsor Investigator should maintain a trial master file that includes the essential documents from each participating site and should ensure these documents are maintained throughout the duration of the study.

Ethical Considerations

Ethical Considerations from a Regulatory Perspective

Important ethical considerations with regulatory support.

Ethical Support we provide:

  • Research Subject Advocate
  • Ethical guidance for protocol, research planning and consent development
  • Training and Educational Opportunities

Request support for ethical considerations from a regulatory perspective by contacting the CTSI-Regulatory Team.

What is a research subject advocate (RSA)?

A research subject advocate is independent of the research team who acts on behalf of a research participant. 

An RSA can:

  • Address concerns regarding a subject’s experience in a research protocol, and can direct any questions, complaints or ideas for improvement of research practices.
  • Be present during the process of consent for high-risk studies, as advised by the Senate Advisory Committee for Human Research Protection.
  • Provide a research participant perspective while planning study protocols.

What Ethical Considerations should be Addressed During Research Planning and Protocol Development

Researchers should approach ethical considerations from a multi-pronged approach and should base their ethical considerations off the Belmont Report, respect for persons, beneficence and justice.

Researchers should consider ethical standards when developing their recruitment plan, identifying their target population, determining inclusion/exclusion criteria, obtaining informed consent, protecting subject confidentiality, identifying risk of harm and evaluating the risk/benefit ratio, and communication of the study results. Research should be based on scientific validity and social and clinical value. 

Human subject research is required to undergo an independent review by an independent ethics committee, such as the Institutional Review Board (IRB).

ClinicalTrials.gov

ClinicalTrials.gov

Support to get your study registered on ClinicalTrials.gov.

Support we provide: 

  • Determining if your study should be registered.
  • Identifying required consent language address the CT.gov registration
  • Guidance for protocol registration and result reporting
  • Troubleshooting for registration and result reporting errors
  • Providing quarterly communication reports to Department Chairs and Associate Deans of Research regarding problem records. 

Request support with ClinicalTrials.gov registration, results reporting, or addressing problem records. 

Additional Tools, Templates and Resources

FAQs

IRB Submission

IRB Submission

Find numerous resources to help navigate the IRB.

IRB Submission Support we provide: 

  • Addressing general IRB questions
  • Regulatory and ethical guidance for how to address or IRB modifications, for initial submissions, amendments, continuing reviews and event reports
  • Regulatory Training and Guidance for Regulatory Compliance Officers outside of the CCRM and CTO

Request support for Essential Documents by contacting the CTSI-Regulatory Team. 

How do I utilize the Multicenter IRB Review?

The Ohio State University is committed to accelerating the IRB approval process for clinical research. This is illustrated through the establishment of:

  • IRB Authorization Agreements
  • IRB Reciprocity Agreements
  • Individual Investigator Agreements (IIAs)
  • Institutional Authorization Agreements (IAAs)

Ohio State has established IRB Authorization agreements to cede IRB review to the following external IRBs:

  • Advarra IRB - for review of some industry sponsored clinical trials
  • National Marrow Donor Program (NMDP IRB) - for review of studies sponsored by the Bone Marrow Transplant Clinical Trials Network (BMT CNT)
  • NCI CIRB – for review of select NCI-sponsored clinical trials
  • WIRB Copernicus Group IRB (WCG IRB) - for review of most industry initiated and sponsored clinical trials

Ohio State has an established IRB Reciprocity Agreement with Nationwide Children’s Hospital that permits Ohio State and Nationwide Children's Hospital to collaborate in the review and oversight of human subjects research that would otherwise require review by both organizations. This agreement applies when an:

  • Ohio State Investigator performs or is engaged in a study at Nationwide Children's Hospital
  • Nationwide Children's Hospital investigator performs or is engaged in a study at Ohio State

The CTSI has an established agreement between Ohio State’s Office of Responsible Research Practices and the eight institutions that compose the three CTSA sites in Ohio, to allow for one IRB to serve as the IRB of record for multi-center clinical research studies involving these CTSA-affiliated institutions which include:

  • The Ohio State University
  • Nationwide Children’s Hospital
  • University of Cincinnati
  • Cincinnati Children’s Hospital Medical Center
  • Case Western Reserve University
  • University Hospitals – Cleveland
  • MetroHealth
  • Cleveland Clinic Foundation


Read Ohio State’s IRB Guide to Establish Ohio State as Your Central IRB


Ohio State has also joined SMART IRB in support of the NIH Single IRB Review policy. SMART IRB is a platform designed to streamline and harmonize the IRB review process for multisite research. This effort was led by our CTSA consortium partner Harvard Catalyst, in collaboration with Dartmouth Synergy and University of Wisconsin-Madison. SMART IRB is intended to serve as a roadmap for institutions to implement the NIH policy on the Use of Single Institutional Review Board for Multisite Research.

SMART IRB

SMART IRB is a platform designed to ease common challenges and burdens associated with initiating multisite research and provide a roadmap for institutions to implement the NIH Single IRB Review policy. Through a flexible master IRB reliance agreement, standard operating procedures and complementary tools and resources, SMART IRB supports and encourages collaboration and harmonization across the nation.

The CTSI aims to apply this “Reliant IRB” model to other collaborative research networks, with a goal to improve efficiencies in the IRB review and study implementation processes without compromising the regulatory and ethical environments that exist within any institution.

Protocol/Consent Development

Protocol/Consent Development

Plan and develop your protocols and your consent documents.

Comparative Effectiveness Research

Comparative Effectiveness Research (CER) is a field of study that utilizes data generation (new studies) and synthesis (comparisons of existing studies) to provide evidence identifying best practices and policies related to improving health care. CER studies are generally conducted after randomized controlled trials (RCTs). RCTs determine efficacy or how well a treatment works under ideal conditions. CER studies examine effectiveness by comparing one or more treatments, procedures or medications to determine what works best for which patients under real world conditions.

Protocol Development

Protocol Support we provide: 

  • Consultation for Required Protocol Elements
  • Development of Data Monitoring Plan, Event Reporting and Protocol Stopping Criteria
  • Detailed Review and Feedback of Study Protocol Formatting from a regulatory and ethical lens
  • Detailed Review and Feedback for consistency between Study Protocol and Consent Form
  • Assistance with addressing FDA, IRB and/or DSMB protocol modifications

Request support for Protocol Development by contacting the CTSI-Regulatory Team.

Protocol development is a collaborative effort between the Study Sponsor, Site Investigator, Biostatistician, the IRB, the FDA and others. The Regulatory Knowledge and Support team can help serve protocol development from a regulatory and ethical perspective. In addition, this team can help ensure consistency with the protocol and consent form and identify logistical barriers to clinical care standard processes. Protocols should be written in a manner that ensures scientific validity and feasibility.  

Consent Development

Informed Consent Form Support we provide: 

  • Consent Form Development
  • Consent Form Review and Feedback
  • Consent Process Guidance
  • Consent Process Witness

Request support for DSMB by contacting the CTSI-Regulatory Team.

In addition to these services, the RKS has consent form boilerplate language for standard medical procedure risks available in the CTSI Research Resources Toolkit.

What is Informed Consent?

Informed consent is an entire process designed to give potential study participants all the information needed so they can make an autonomous decision about participating in a research study.  

It starts with the initial introduction of the study and doesn’t end until the participant completes their study participation or declines their study participation. Informed consent is an ongoing process.

Informed consent typically includes obtaining a signed informed consent form, although in some rare cases, consent may be provided through other means. The process in which informed consent is obtained must be IRB approved prior to implementation of that informed consent process. 

What is Required to be included in the Informed Consent Discussion and Consent Form?

Federal Laws (45 CFR 46 – Common Rule and 21 CFR 50 – Protection of Human Subjects) indicate the required basic elements of informed consent and when appropriate, the additional elements of informed consent. The basic elements must be included in the consent form and discussed during the consent process and the additional elements should be included when appropriate.  

Researchers should refer to the Ohio State Office of Responsible Research Practices Informed Consent Process and the Elements of Informed Consent policy for additional information regarding the informed consent discussion and consent form requirements.

Which Informed Consent Template should be used?

Researchers should use the IRB of Records Informed Consent form template, while ensuring all elements of informed consent and any institutional required language are included.  

If Ohio State IRB is the IRB of Record, researchers should use the Ohio State IRB ICF Templates and Guidance.

IND/IDE Support

IND/IDE Support

Helping research teams navigate the investigational new drug approval process.

Regulatory Guidance for Academic Research of Drugs and Devices

Clinical Trials for drugs being developed for initial use in humans as well as for FDA approved drugs but being investigated for additional use(s) require an Investigational New Drug Approval (IND) from the FDA prior to commencing.

For clinical trials involving marketed drug(s) for alternative use an IND Exemption (PDF) may be an acceptable alternative. The CTSI, in collaboration with the Ohio State Drug Development Institute and Nationwide Children’s Hospital’s Drug and Device Development Services, can help research teams navigate these potentially complex processes.

IND/IDE Support we provide:

  • Meetings with the FDA (INTERACT, Pre-IND, Q-sub: Pre-Sub)
  • IND Submission Packet Templates
  • IDE Submission Packet Templates
  • Expanded Access “Compassionate Use” submissions
  • Clinical Hold Responses
  • Guidance and training for preparing IND/IDE initial submissions, amendments/supplements, annual reports, and withdrawals/terminations
  • Full preparation of IND/IDE submission packets
  • Guidance with determining device risk level and classification (Note: The study sponsor maintains overall responsibility for making the final determination in collaboration with the FDA and IRB)

Request support for IND/IDE submissions and FDA meetings by contacting the CTSI-Regulatory Team

When conducting human research with an investigational drug or device (drugs or devices that have not been approved or cleared by the FDA for marketing) researchers need to obtain an exemption from the pre-marketing approval requirements in the Food Drug and Cosmetic Act, prior to starting the research. This is obtained through the Food and Drug Administration (FDA) by submitting an Investigational New Drug (IND) Application or an Investigational Device Exemption (IDE). 

Once an IND is submitted to the FDA the sponsor must wait 30 days to begin the research, or until they receive a study may proceed letter.  Within that 30 days the FDA may issue a clinical hold until specific items are addressed.

Once an IDE is submitted to the FDA the sponsor must wait 30 days to begin the research, or until they receive an approved or approved with conditions notification from the FDA.  Within that 30 days the FDA may issue a disapproval of the research or require specific conditions be met in order to conduct the research. 

IND/IDEs need to be maintained throughout the protocol lifecycle through the submission of amendments/supplements, annual reports/progress reports, safety reports and IND/IDE termination or withdrawal.

FAQs

NIH Requirements

NIH Requirements

Support in navigating NIH requirements.

NIH Requirement support we provide:

  • Regulatory Consultations for CTSI Funded proposals (Pilot, Element E, KL2, T32)
  • Submission of CTSI Funded proposals to NCATS for Prior Approval
  • Guidance and Consultation regarding other NIH requirements

Request support for NIH requirements by contacting the CTSI-Regulatory Team

What is included in a Regulatory Consultation for CTSI Funded Proposals?

During your regulatory consultation a regulatory professional will obtain a brief description of the study from you and ask you questions about your proposed project. They will help identify the regulatory needs of your project and help link you to other resources, such as community engagement and recruitment and retention.

Additionally, the regulatory professional will help provide guidance for any required submissions, approvals, or authorizations needed for your project, including the IRB, NCATS, FDA, Research Stakeholders, IBC and IACUC.

Do all CTSI Funded Projects Require NCATS Prior Approval?

All human subject research and vertebrate animal research projects require submission to NCATS.  Any human subject research that fits under Category 1 will require prior approval from NCATS before the project can begin. Your regulatory professional will help you identify what is required for your CTSI funded project.

What other NIH Requirements Support can CTSI Provide?

Regulatory professionals can help provide guidance for researchers to meet the NIH Policies, for their NIH funded project. NIH has general policies and announcements, but important to note that each NIH Institute may have their own individual policies and requirements, such is the case for Data Safety Monitoring. 

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