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

Pre-Award

Pre-Award

Steps to complete and consider before funding is secured.

Training

General Research Knowledge

Ohio State requires all faculty, staff and students who are eligible to conduct research to be trained in the Responsible Conduct of Research (RCR) through the online Collaborative Institutional Training Initiative (CITI) RCR course. If you are working with human subjects the following courses need to be completed with up-to-date certification: Good Clinical Practices, Human Subjects Protection and Responsible Research Practices. Documentation of completion will be filed in the study regulatory folder.


Biological Specimen Collection, Handling and Storing

Research studies working with specimens should provide a lab manual with details needed to be successful in doing your job. Knowing specific details to collect, process and store the specimens should be understood prior to beginning work. The Comprehensive Cancer Center (CCC), Clinical Research Center (CRC) and others have teams dedicated solely to biospecimen services.


When you need to process your own specimen the following items need to be outlined and understood:

Clinical Skills

Do you have the correct skills to complete research studies? Basic clinical skills training in EKGs, vital signs and phlebotomy is available in Buckeye Learn: search Phlebotomy, EKG and Vitals and select Ambulatory Skills Orientation and Review. Classes consist of an online lecture and practice and will take around four hours per skill depending on class size.

Quality Management

Industry sponsors provide monitoring to ensure safety of subjects, data integrity, quality and compliance and they typically have an internal Quality Management Plan and a Data Safety Monitoring Plan (DSMP). Not all sponsors provide study monitoring. Just because it is not provided by the sponsor does not mean it should not be completed. Good documentation drives good clinical research. A competent clinical research coordinator is trained to know, “If it is not documented, it does not exist.”  

The CTSI offers independent monitoring and audit services to ensure your study is meeting quality plans.  

If your study does not have a budget to pay for independent monitoring it can be completed by the study team. Self-monitoring should be implemented in studies not otherwise monitored by sponsors or contract research organizations. These are most commonly investigator-initiated studies but also include some foundation and federally funded projects. 

The goal of self-monitoring is to ensure that the following seven elements are evaluated within the research protocol:

  • Subject Safety: monitoring is conducted to avoid or minimize risks (i.e. physical, psychological or social)
  • Data Integrity: monitoring is conducted to ensure data is accurate and complete. Monitoring of data assures adherence to the approved clinical study
  • Subject Privacy: monitoring is conducted to ensure individual’s rights are protected
  • Data Confidentiality: monitoring is conducted to ensure data is secured
  • Product Accountability: monitoring is conducted to ensure drug(s) or device(s) are tracked and accounted for
  • Study Documentation: monitoring is conducted to ensure that required documentation and reports are on file, accurate and complete
  • Study Coordination: monitoring is conducted to ensure that investigator delegation and communication with the research team are planned and systematic

Self-monitoring can be done by a designated internal clinical research compliance auditor or by developing internal checks and balances (e.g. a buddy system among coordinators in the same department).  

Any deviations noted during the review process should be noted through a note to file, and addressed through departmental change processes, policies or the continuing education/retraining of staff on processes and policies. Some might need to be reported to the IRB or have a CAPA created.  

ALCOA-C

During the review the monitoring team should always be vigilant to ensure the study team is following ALCOA-C (Attributable, Legible, Contemporaneous, Original, Accurate, Complete) for their study documentation. These are the attributes or dimensions considered of universal importance for the data integrity of source data and the records that hold those data. 

  • A-Attributable (to both subject and to any actor on a record- monitors should be able to tell who recorded the data, who made a change and why);
  • L-Legible (available for human review, possible to read electronically if an encoded Record);
  • C-Contemporaneous (timing of data collection with respect to the time the observation is made: the more promptly an observation is recorded, the better the quality, signatures much come with a date);
  • O-Original (the first suitably accurate and reliable recording of data for the intended purpose);
  • A-Accurate (free from error, especially as the result of care; an accurate diagnosis conforming exactly to truth or to a standard).
  • C- Complete- maintain adequate, accurate and complete source documents at the time of collection do not wait a few days or a week to record

NOTE: ALCOA stems from a talk with Dr. Stan Woollen, the Food and Drug Administration (FDA), in the early 90’s on earmarks for the quality of records and has become a widespread acronym reflecting best practices for clarity and usability of data.

Other Tools and References

The FDA put out guidance for Industry sponsored studies titled A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers (PDF).

The National Institutes of Health (NIH) states “oversight and monitoring of all intervention studies to ensure the safety of participants and the validity and integrity of the data” is required. NIH policy states "monitoring should be commensurate with risks, size and complexity of the trials.” NIH also emphasizes “the elements of the monitoring plan may vary depending upon the potential risks, complexity, and nature of the trial.”

References: NOT-OD-00-038 (release date June 5, 2000) and NOT98-084 (release date June 10, 1998)

Many NIH divisions have created templates for different aspects of monitoring/review for studies. 

The Office for Human Research Protection (OHRP) Code of Federal Regulations (45 CFR 46.111) states: “When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of the subjects.”
Reference: 45CFR46

The U.S. Food and Drug Administration (FDA) states: "Sponsors of clinical investigations involving human drugs, biological products, medical devices and combinations thereof are required to provide oversight to ensure adequate protection of the rights, welfare and safety of human subjects and the quality of the clinical trial data submitted to FDA."
Reference: UCM269919

Department of Defense (DoD) Instruction (DoDI) 3216.02 previously required that IRBs approve an independent Research Monitor (RM) with specific roles and responsibilities for all Greater Than Minimal Risk (GTMR) research supported by theDoD. The April 15, 2020 revised DoDI 3216.02 no longer includes the RM requirement.

Data/Safety Monitoring Board

The Data Safety Monitoring Board or Committee consists of external experts to the trial in the field of research tasked with reviewing data integrity and safety. Often these committees also include biostatisticians, clinical research experts and research ethicists. This committee functions as an independent group tasked with the responsibility to continually review the safety of the research study. Through this review, they also assess the scientific integrity and validity of the research study. This group can make recommendations on the conduct of the study to the IRB, Investigator and Sponsor.

The CTSI has a robust DSMB. Schedule a regulatory consult with the DSMB Program Manager at the CTSI. Please email CTSI-Regulation.

Templates / Resources

The Ohio State University Comprehensive Cancer Center-James DSMP
DSMB Training Manual for Investigator-Initiated Studies (PDF)
NIH: Guidelines for Data and Safety Monitoring
FDA: Establishment and Operation of Clinical Trial Data Monitoring Committees (PDF)
HRPP Policy on Data and Safety Monitoring (PDF)

Recruitment Planning

Recruitment and retention, begins with the first contact that a potential participant has with your study. Each protocol is unique, but the first impression the public has of your study is the most important. The CTSI can help you make that best first impression by discussing best practices and assisting in the development of brochures, flyers, mailings, surveys, posters, newsletters and appointment reminder strategies for IRB approval. The CTSI can also help you strategically plan for recruitment of special populations. It is essential to consider your recruitment and retention plan in the development of your budget. Contact MyCTSI for more information.

Budgets

To properly negotiate budgets for research studies it is important to assess protocol feasibility and identify the costs to conduct the study. A study should not be pursued if it does not cover the costs unless additional financial resources are identified.

The first step to create a comprehensive budget is to use an Internal Budget Template (Excel Document) to develop a budget that identifies all costs to conduct a study and can be used as a tool to negotiate sponsor budget. It is critical to have a thorough understanding of the study documents to develop a comprehensive budget. This entails reviewing the protocol, contract, consent and case report forms to identify each procedure, visit, participant contact, supplies and patient care costs that are needed to conduct the study. It is recommended to identify the work that is required per participant. All the identified items should be listed in the internal budget. It is critical to meet with the study team who will be performing the work to understand the burden of each task.  

Once all items are identified to conduct the study, a determination needs to be made if the service is considered Standard of Care (SOC) or Research Only. Standard of Care services are those that are typically performed in the participant population for the disease being studied and will be billed to the patient/insurance. Research Services are those that are performed for research purposes only. Research services are NOT billed to the patient/insurance. Mark the SOC and Research determinations in the internal budget. The Research services will be the costs to conduct the study.

Other Items Essential to Consider:

  • Start-up Costs
  • Staffing: investigator, coordinator, nurse etc. consider percentage of time to do all parts of the study that are not listed on the schedule of events
  • Administrative Support: project management, data management
  • Supplies and Equipment: example venipuncture supplies, EKG electrodes, shipping materials (equipment such as -70 freezers or special imaging scanners may be needed for certain studies)
  • Travel: staff to investigator meetings or trainings
  • Recruitment Costs: subjects travel and stipend, recruitment plan
  • Subcontracts, Consultant Agreements
  • Cost Sharing 
  • Overhead Cost

It is important to note that one size does not fit all when it comes to budgeting. There are many different types of studies and sponsors who all have different budgeting needs. ERIK discusses the common budgetary core components to developing a study budget. The CTSI can help review your budget to ensure you have captured all of the areas in your research proposal.  


Patient Care Cost Estimates and Medicare Analysis

The Research Operations Web Application (ROWA) is an electronic application that is used to do one of two things:

  1. Determine research rates (costs) for research related study procedures. These costs will only account for research rates that are billable by: - Ohio State Health System
    - The Ohio State Faculty Group Practice Plan (FGP)
    - Ohio State Physicians (OSUP)
    - Obtain IHIS Access for Research
  2. Obtain IHIS Access for Research
  3. Complete your Medicare Analysis Form

Other research related costs will need to be accounted for when preparing the clinical trial budget.


Research Rates through ROWA

The Research Billing Office (RBO) is responsible for quoting research rates for services that are billable by the Ohio State Health System, the Ohio State Faculty Group Practice Plan (FGP) and Ohio State Physicians (OSUP).  

Research rates for the Wright Center of Innovation can be obtained by contacting Melanie Hughes at 614-293-9998. Also please note that the Information Warehouse (I.W.) has separate billing/fees for copies of radiology exams, digital images, etc.

NOTE: The Center for Clinical Research Management (CCRM) or Clinical Trials Office (CTO) will manage the generation of research rates and budget development for most clinical trials, if your research group is part of the CCRM or CTO. If you are part of one of these groups, please reach out to your study implementation or finance team. 


IHIS Study Activation through ROWA

Researchers not under the umbrella of the CCRM or CTO can activate their study in IHIS using ROWA. This activation is needed to ensure the appropriate research billing is taking place and that the study patient is not charged for research related procedures. Compliant billing is required for all research.

To activate the study in Integrated Health Information Systems (IHIS): 

  • The user will first need to enter the new study information in ROWA
  • Then the user will need to click the “Register” button to provide additional study details that are required to build the research record in IHIS
ROWA Log-in
Email the Research Billing Office

Contracts

Confidential Disclosure Agreement

In order to ensure the protection of confidential information shared for research studies between Ohio State and a sponsor, a Confidential Disclosure Agreement (CDA) or Non-Disclosure Agreements (NDAs) may be executed. These contract agreements are only allowed to be completed by the Office of Innovation and Economic Development (formerly known as Technology Commercialization Office). The CDAs cannot to be signed by individual researchers or investigators. 


Materials Transfer Agreement

Research materials, such as human specimens or other biological materials, are often exchanged between The Ohio State University and other academic institutions and commercial entities. To exchange these materials between Ohio State and another entity, a Material Transfer Agreement (MTA) must be completed. This agreement defines the legal rights of each entity in the transfer of research materials.

The Ohio State University Office of Innovation and Economic Development is responsible for the negotiation and review of MTAs. They assist with preparation and execution of these documents. Every MTA is required to be signed by an authorized signatory for the university and can only be done through the Office of Innovation and Economic Development.

IND/IDE

The drug development process is time consuming and expensive. It is estimated that of the 5,000 new molecular entities (NME) developed only five make it to clinical testing and only one of the five actually receive FDA approval.

The Investigational New Drug (IND) is an application that sponsors must submit to the FDA to receive an exemption to transport or distribute drugs across state lines. The IND must state the purpose to test the agent in human subjects and supply pre-clinical data and justification to warrant clinical studies. The application must be submitted prior to the start of any human subject research studies. The research study cannot begin participant recruitment until 30 days after FDA receipt or after all FDA requests have been fulfilled. INDs require annual updates to reflect protocol changes, new information or serious adverse events.  

Investigational Device Exemption (IDE) is the term most often associated with usage of a device in research. Medical devices distributed in the United States must comply with the following regulatory requirements: Establishment Registration; Medical Device Listing; Premarket Notification 510(k), unless exempt, or Premarket Approval (PMA); Investigational Device Exemption (IDE) for studies; Quality Systems Regulation; Labeling Requirements; Medical Device Reporting (MDR).   

It can be confusing to know what approach to take and what paperwork is necessary.  The CTSI has experienced staff that can help with this process. Please email CTSI-Regulation or visit IND/IDE.

Authorization to Seek Off-Campus Funding (ePA-005)

The ePA-005 is an internal form that provides the PI with all required permissions to submit a proposal for funding. The ePA-005 has two purposes: (1) It documents administrative, budgetary and compliance information about the proposal and provides chairs, center directors and deans with a summary of this information; and (2) Campus signatures on the form authorize the Research Foundation to submit the proposal (on behalf of the PI) to an external sponsor. 

A fully signed ePA-005 must be provided to the Office of Sponsored Programs (OSP) for every proposal to be submitted to an external sponsor. Talk with your grants management or department fiscal office to find out who initiates the form.