Section I. Introduction and Purpose of the Guide to Clinical Research at USC

Dear Research Colleagues at the Keck School of Medicine,

On behalf of the SC Clinical and Translational Science Institute, we are excited to provide this Guide to Clinical Research to help introduce and describe the clinical research processes here at USC. 

The purpose of this Guide and the corresponding ancillary documents is to provide a clear, user-friendly overview of conducting human studies research at USC and the Keck School of Medicine. The audience for these materials is investigators and research personnel at USC and the Keck School of Medicine.

If you are new to USC, you can use the New Study Navigation Tool to help you get started. This tool provides information about which offices you’ll need to engage with in order to activate your study. Sections II and III provide an overview to help you activate your clinical study at USC.  

In addition, the SC CTSI provides free research navigation services to all faculty, staff, and students. If you have any questions, contact Clinical Research Support at 323-442-CTSA or crs@sc-ctsi.org.


Finally, this document is dynamic and meant to be updated regularly as processes change and new information becomes available. Updates and suggestions for content can be emailed to: crs@sc-ctsi.org

Our hope is that you will find this guidance useful at every stage of the research process, from study start-up to closeout. We thank you for your commitment to our institution and for conducting groundbreaking, important clinical research that has real-world impact for our local communities.

Wishing you and your team the best of luck in all of your research endeavors. Fight on!

Sincerely,

April W. Armstrong, M.D., M.P.H. 
Associate Dean for Clinical Research 
Keck School of Medicine of USC

Lily Jara, B.S.
Clinical Research Coordinator Supervisor 
SC Clinical and Translational Science Institute


Section II. Quick Start for Activating Non-Industry Funded (e.g., Federally Funded and Foundation Funded) Clinical Studies at USC

For a general overview of the clinical research initiation process for new or junior investigators, see the figure below. Note, this Guide to Clinical Research will elaborate on each aspect of this figure.

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A non-industry study receives funding from federal agencies such as the National Institutes of Health (NIH), Department of Health and Human Services (HHS), Department of Defense (DOD), and non-profit foundations. This process map below provides the necessary steps to activating a non-industry funded clinical study “at-a-glance.” 

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For PIs applying for non-industry funding, the process is as follows:

●        PI submits the proposal and initial budget for internal review through Kuali Coeus (KC) (through June 2021). They must attach the Scope of Work (SOW), preliminary budget, budget justification, and any other documents required by the sponsor.

●        In parallel, the PI may seek out advice on budget preparation from the CTSI budget specialist Joanne Pak.

●        The PI then submits the proposal in KC, and it is routed to the Department for approval if the Department is within the Keck School of Medicine (KSOM).

●       If the proposal and preliminary budget are approved by the Department within KSOM, the Department of Contracts and Grants (DCG) reviews and approves the proposal. If changes are requested, the proposal is routed back to the PI to make the necessary changes. If changes are not required, the PI submits to the sponsor, and the sponsor assigns a funding score.

●        If the proposal receives a fundable score, a confidential disclosure agreement (CDA) may be required by the sponsoring organization, and will be executed between the sponsor and USC. Sometimes a CDA is referred to as a non-disclosure agreement (NDA), though the function is the same. CDAs are typically not required for federally-funded studies. In the case that a CDA is required, the funding agency will let the PI and/or study staff know that a CDA must be executed before any study-specific information can be released.

Resources for proposal preparation, including what proposal guidelines, budget development guidelines, and more, can be found here

Budget Preparation Support: For guidance on preparation of study budgets for non-industry funded human studies, especially for federal grant applications, contact CTSI budget specialist Joanne Pak at 323-442‑7278, or by email at Joanne.Pak@med.usc.edu

In the event that a CDA is required, the funding agency will not release the protocol and/or study related information to the PI until the CDA or NDA is executed.

The CDA/NDA may be a one-way (unilateral) agreement that requires only the receiving party to maintain secrecy. For example, a funding agency may provide information to a PI so he/she can determine if he or she would like to participate in a study. The CDA or clause may also be a two-way or mutual agreement in which both parties exchange confidential information and are obligated to maintain secrecy. Regardless of whether the agreement is unilateral or mutual, information provided to USC under the agreement cannot be disclosed to a third party or may be limited to persons within USC on a need-to-know basis.

Access to confidential information must be limited to personnel who need the information to perform the study, work with patients, or work with ancillary groups. The information should never be shared outside of USC, and should only be shared with others at USC if they need to know the information, and if they are informed that the information is confidential. PIs and CRCs alike are responsible for protecting confidential information. Consult USC’s Guide to Confidentiality for further information.

Regarding the process for executing the CDA, the PI or member of study team submits the CDA via KC for non-industry sponsored clinical studies. During the KC routing and approvals process, the PI will be required to approve the CDA submission. For lead units in KSOM, it must also be approved by the department/division designee and the School designee. DCG will then review and negotiates the CDA with the sponsor. Upon agreement, DCG determines if PI signature is required. If required, DCG routes the CDA for signature. After the PI signs, DCG executes and distributes the CDA. 

USC Department of Contracts and Grants:

213-740-7762; List of DCG staff and contact information

After the CDA is executed (when deemed necessary by the funding agency), the budgeting process begins. For non-industry sponsored studies, DCG can be involved in the proposal submission, award review, and approvals process. However, in many cases, the PI is responsible for the submission of the proposal to the funding organization. If the study is NIH-funded, the DCG (rather than the PI) must submit to the funding agency. For other funding organizations and for foundation funding, the DCG reviews the application in KC. Once DCG approves the application within KC, DCG alerts the PI and study team that they are permitted to proceed with the submission process. 

Contract and Budgeting Process Guidance Map
This guidance map below provides information about which office handles which aspects of the budgeting and contracting process based on two metrics: the study’s funding source, and whether or not the study will use hospital resources, such as clinic rooms, pathology, etc. 

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1. Non-Industry Contracting Process 

For federally funded and non-industry funded studies, DCG may be responsible for reviewing, approving, and submitting the proposal to extramural sponsors. See Section II, D. Contract and Budgeting Process for an explanation of when DCG submits to the funding agency versus when the PI submits to the funding agency. DCG also negotiates and accepts awards on behalf of USC, executes subcontracts, coordinates pre- and post-award actions, and more. DCG uses KC for proposal and award management.

If the funding source is non-industry, DCG will assist with contract negotiation, budget, and submission via KC PreAward. If the study uses health system resources, such as procedures done in the Keck Medical Center, DCG will assist with contract negotiation, and submission via KC PreAward. CTO will provide pricing for clinical activities and procedures, as well as perform the Medicare Coverage Analysis (MCA). The study’s Department must manage budget development.

2.  Budgeting Process 

Following the proposal initiation, submission process, and the CDA process (when the funding agency deems it necessary), the CTO will begin conducting a Medicare Coverage Analysis (MCA). An MCA is a requirement for all clinical studies in which there are tests, procedures and interventions that are associated with research, and an MCA is required for studies that use hospital resources. Examples of hospital resources include use of clinic rooms, pathology services, and more. MCAs are performed for all clinical research studies, irrespective of their funding source. The MCA must be completed for such studies prior to contracting and prior to enrollment of study participants. During an MCA, the CTO coverage analyst will review the protocol for any clinical services to determine which can be reimbursed by Medicare or as part of Standard of Care (SOC). Following the completion of an MCA, the PI will receive a study-specific billing summary that itemizes all clinical services to be provided to the patient as part of the research, and the analyst will specify which services should be billed to the study sponsor, and which can be billed to Medicare. As a general rule, clinical services that are strictly part of the research study will be billed to the sponsor, whereas services that are part of the standard of care that the patient would receive anyway are billed to Medicare or the patient’s insurance. 

Medicare Coverage Analysis Process:

● Once the internal OnCore submission is completed, CTO conducts coverage analysis 
● PI should review and approve coverage analysis determination showing services and activities that will be paid by sponsor, insurer, or other USC account 
● Once the study is activated by CTO’s budget specialist in OnCore, the study team must conduct clinical trial in accordance with approved protocol and the Clinical Trial Agreement (CTA). (The study team cannot begin the study until formally notified by the IRB that the study can begin.)

For non-industry funded studies, the award is forwarded to the Sponsored Projects Accounting (SPA) group, and they set up the account in KC. The account number is then inputted to OnCore. After the appropriate documents are processed, the study can proceed to the next step, which involves IRB approvals. (The budgeting/contractual and IRB processes may occur simultaneously when allowed by the funding agency).

1. USC Clinical Trials Unit (CTU)
The USC Clinical Trials Unit (CTU) provides the infrastructure, resources, and support to conduct human studies, with a focus on early phase and complex mechanistic trials. CTU can assist study teams with accommodating patient visits for high intensity trials that involve serial blood draws, infusions, and monitoring. The CTU also has trained clinical staff like research nurses, phlebotomists, radiology technicians, and more. The staff is highly experienced in collecting and processing PK and PD samples in a timely and efficient manner.

CTU: Yolanda Gutierrez, Assistant Director for Clinical Research Operations; 323-865-3056; cerda@med.usc.edu or ctu@sc-ctsi.org

The CTU also offers a specimen-processing center that offers a variety of services and serves as a one-stop unit for processing, storing, and shipping research samples collected from research patients. The USC CTU has the capability to provide X-ray absorptiometry (DEXA) for body composition or bone densitometry studies. The CTU also provides specimen collection and processing services that may include blood, saliva, sputum, urine, stool, hair follicles and other types of specimens. In addition, the CTU Processing Center can perform specialized processing for studies in which the assays are run in the investigator’s lab, research core lab, or sponsor’s central lab. Specimen processing may include the following: Serum/plasma separation, buffy coat separation, custom labeling, centrifuging, aliquoting, blood smear, PBMC separation; assistance with shipping & handling (ambient, refrigerated, dry ice). To learn about the CTU’s full capabilities, click here.

CTU Laboratory: Lilit Baronikian, CTU Lab Supervisor, 323-865-3379 (office) or 818-642-4838 (cell), yegiyant@med.usc

2. USC Investigational Drug Services (IDS) Pharmacy
IDS Pharmacy supports human studies involving investigational products and supports safety and care for research participants in both the inpatient and outpatient areas. IDS Pharmacy integrates its activities with the clinical, safety, informatics, administrative, and drug distribution systems of the hospitals and clinics to optimize investigational product therapy for patients. IDS Pharmacy assists with regulatory compliance, integrity of blinding and randomization, dispensing of investigational products, temperature monitoring, and more. 
Coordinating with the IDS Pharmacy early on is crucial to ensuring that they can accommodate requests for creating, storing, and dispensing the study drug, even during the site qualification phase. If the study requires the use of an investigational product, the PI will need to involve the IDS Pharmacy.
You should contact the IDS Pharmacy via e-mail as soon as you have identified that your study involves investigational product (ideally before IRB submission). They will respond within 1-2 business days and draft a scope of service agreement that details your study’s pharmacy fees depending on whether it is industry-sponsored, government-sponsored or investigator initiated.  
It may be necessary to set up a site qualification visit. If so, the study team should contact, inform them of the items to be assessed during the site qualification visit, and work with them to prepare accordingly. The study team should provide additional information to the IDS Pharmacy that will help them determine how feasible it will be for them to take on the study. For example, providing information about the estimated number and size of the study kits or investigational drug that needs to be stored, how frequently they will be shipped, and how the drug will need to be dispensed and stored will be helpful to the IDS team. 
If on-campus pharmacies are unable to accommodate, it will become necessary to explore other options such as third-party pharmacies near HSC campus to see if they can assist with storing and dispensing the drug. There are local third-party compounding pharmacies that can assist with dispensing drugs, and other compounding pharmacies around the U.S. that can assist with creating drugs and placebos. Their fees will depend on the details of the study. 

IDS: PIs should contact the IDS Pharmacist (idspharmacy@med.usc.edu, 323-865-3538) to determine study feasibility and budget requirements. Depending on the protocol, pharmacy services may be conducted at the IDS Pharmacy or transferred to satellite sites (such as Keck Hospital of USC or Norris Cancer Hospital).

Other Pharmacies: For a list of possible pharmacy options beyond those at HSC, contact the SC CTSI CRS group at crs@sc-ctsi.org

3. Radiology & Imaging
Radiology and imaging services are available at the Norris Cancer Center and at Keck Hospital (Healthcare Consultation Center II and the PET Center in Healthcare Consultation Center I). Patients recruited from LAC+USC may be imaged at HCC2 or the PET center only if funding is available. The process can be initiated while the study is under review by the IRB. However, no research scans may be scheduled until the study has final IRB approval, which is contingent on RSC approval. In addition, research scans can’t be scheduled until ROF is available and Radiology Scan Request form (if applicable) is completed. Radiology research imaging charges are determined by the coverage analysis performed by the CTO. Please note there is a charge by the Department of Radiology for completion of RECIST tumor flow sheet form by a radiologist. Please make sure CTO is aware and prepares your budget accordingly.

Radiology: The coordinator will send an email to Bhushan Desai (bhushand@usc.edu; 323-865-9949) or contact the Department of Radiology at 323-442-8541, outlining the imaging requirements for the study and provide any additional materials (i.e., imaging manual). Imaging can be requested using the Research Order From created by the Clinical Trials Office. 

Imaging
Center for Image Acquisition
The Center for Image Acquisition, part of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute, houses MRI equipment used for neuroimaging. The Center has other equipment to help PIs conduct scans that ensure the comfort for participants. Click here for a full list of equipment and capabilities.
CRCs can schedule appointments with the Center by creating an account under the “For Investigators” tab. The following information will be needed for the application: project name, proposal number, PI name, anticipated start date, copy of IRB approval letter, copy of study budget showing scan costs. Once the application is approved, login credentials will be provided, and users will be able to schedule online. Investigators preparing budgets for new proposals should contact the center to obtain the latest rates for scans and other services. Please allow at least 2 weeks for rate requests to be approved. 

CIA: Direct any questions to CIA@ini.usc.edu.

Molecular Imaging Center – Radiochemistry/Cyclotron Labs
The Molecular Imaging Center (MIC) is a comprehensive imaging program focused on the development of various types of PET tracers used for imaging disease. The facility includes a Cyclotron GMP facility, PET radiochemistry laboratories, access to small animal imaging, and access to clinical PET/CT imaging facilities.
PIs interested in utilizing these services should contact Peter S. Conti, MD, PhD to set up an initial meeting to discuss the feasibility of the study, the radiotracer availability/preparation and clinical trial enrollment. Clinical imaging studies will be performed under pre-IND, IND or approved drug protocols at HCC-I. Opportunities for early-phase clinical trials and multi-center trials are available at MIC including existing trials in the following areas:

Oncology:
● Breast Cancer
● Prostate Cancer

Neurodegenerative Disease:
● Alzheimer’s Disease
● Parkinson’s Disease

Cardiovascular Disease:
● Cardiac Ischemia

MIC: Peter S. Conti, MD, PhD. 323-442-3858 / peter.conti@med.usc.edu and copy miclab@usc.edu.

4. Pathology
The point of entry for all human biospecimen procurement needs is the Translational Pathology Core Facility (TPCF) of the USC/Norris Comprehensive Cancer Center, including whether for clinical trials, non‐interventional translational research studies, basic research studies, and whether cancer‐related or not. In this capacity, the TPCF works closely with the hospital‐based employees of the LAC+USC Medical Center and the Keck Medical Center to facilitate the process of research tissue acquisition and processing and to insure compliance with federal, state, and local hospital regulations. The activities of the TPCF are supported by chargebacks to the study PI. Any investigator may request services from the TPCF, and Cancer Center members receive services at a discounted rate. Specimens can be obtained by USC investigators with IRB approved, funded studies with a valid Lab Agreement.

For all research studies requiring the use of human biospecimens, including both clinical trials and non‐interventional (non‐clinical trial) translational research and basic research studies, investigators must submit the Laboratory Agreement Request Form in order to obtain approval to procure biospecimens. The Laboratory Agreement Request Form must only be submitted after funding and IRB approval have been obtained, Once the Lab Agreement is approved, the investigator will meet with Pathology to arrange the implementation of the biospecimen procurement, processing, and distribution required by the protocol.
 
For clinical trials, once the trial is opened, two additional forms will enable investigators to request procurement from individual patients: Request for Formalin Fixed Paraffin Embeded (FFPE) Slides/Tissue Blocks and/or Request for Fresh/Frozen Tissues can be obtained from and submitted to Ms. Chen. 

Types of human biospecimens available for research: 
1) Formalin-fixed, paraffin-embedded (FFPE) tissues: 
All tissues taken during clinical care are saved for a period of time in the hospital archives in the form of FFPE blocks. These can be used for research purposes provided appropriate consent and IRB approval have been obtained. At Keck Medical Center, these tissues are stored indefinitely. At LAC+USC, the FFPE tissues are stored in the hospital archives for 10 years, at which point they are donated to the Population Based Tissue Arm of the TPCF. TPCF personnel can assist with procurement and sampling (e.g., sectioning, coring) of FFPE blocks in the hospital archives. 
2) Fresh, fresh/frozen, and fluid specimens (e.g., whole blood, serum, plasma, buffy coat, and urine):
Fresh, fresh/frozen and fluid biospecimens can be collected prospectively for IRB approved, funded studies with a valid Lab Agreement and patient Informed Consent. Typically, both tumor and matched normal tissue are collected immediately after explanation under the supervision of the service pathologist/PA. The TPCF personnel will assist with the immediate processing and storage of the specimens, banking, tracking, distribution, and processing of specimens required for analysis.

Pathology: List of contacts for the service/core, click here or email Sue Ellen Martin, MD, PhD, director; sue.martin@med.usc.edu

In order to initiate the IRB application submission process, the study application and protocol will need to be submitted to iStar. All co-PIs must agree to participate in the study before the PI can submit the application to the IRB for review. The application needs to be approved by the PI or co-PI in order to finalize submission, after which the Division/Departmental must approve the application in order to route the study for IRB review. IRB Staff are then assigned to conduct a cursory review.

All investigator-initiated non-cancer clinical trials that have not undergone prior scientific review by a qualified scientific body are automatically routed to the SC CTSI Clinical Research Support Scientific Protocol Review Committee to undergo scientific and feasibility review as a part of the IRB review process. More information regarding the Scientific Review process can be found in Section V. IRB Approvals Process, subsection E.

After scientific review is complete or not deemed necessary, the IRB administrator categorizes the study as Full Board, Expedited, or Exempt. If the study is subject to Full Board Review, as is true for most clinical trials, the study will be assigned to a Committee Review. During the Committee Review Process, the board members will conduct independent reviews, followed by a Committee Meeting during which the study protocol and corresponding risks are discussed.

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If the IRB has questions or issues with the protocol, contingencies will be given to the PI and study team. A contingency is an item from the IRB that must be addressed in the next submission before the IRB can approve the study. When responding to the IRB, it is best to err on the side of caution and explain the decision-making and study processes in more detail rather than less so that the analyst and/or board can understand the rationale without having to ask for clarifications from the PI and study staff. Once all contingencies have been adequately addressed, the IRB will approve the protocol within iStar. The approval comes in the form of an IRB approval letter uploaded to iStar that outlines what was approved. However, it is important to note that IRB approval does not necessarily mean that the study can begin, especially in the case of industry-sponsored trials. Once the contract is finalized, the the IRB will re-issue an approval, indicating that the study can begin. At this time, the IRB will also release the approved and stamped ICFs.

Upon release, the IRB approval letter and ICF is approved for one year from the release date. If the study plans to continue past one year, continuing review must be completed. More information about continuing review is found in the Appendix. If the study closes after one year, more information about that process is also found in the Appendix. More information on the USC IRB and the Office for the Protection of Research Subjects (OPRS) can be found here.

IRB: 323-442-0114; IRB@usc.edu.


Section III. Quick Start for Activating Industry-Funded Clinical Studies at USC

For a general overview of the clinical research initiation process for new or junior investigators, see the figure below. Note, this Guide to Clinical Research will elaborate on each aspect of this figure.

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Industry-sponsored studies are funded by pharma or other for-profit entities and USC receives a protocol to carry out, which was written by the for-profit entity. This process map provides the necessary steps to activating an industry-funded clinical study “at-a-glance.” 

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For industry-sponsored trials, the sponsor will not release the protocol and/or study related information to the PI until a confidential disclosure agreement (CDA) is executed between the sponsor and USC. Sometimes a CDA is referred to as a non-disclosure agreement (NDA), though the function is the same. 

The CDA/NDA may be a one-way (unilateral) agreement that requires only the receiving party to maintain secrecy. For example, a sponsor may provide information to a PI so he/she can determine if he or she would like to participate in a study. The CDA/NDA or clause may also be a two-way or mutual agreement in which both parties exchange confidential information and are obligated to maintain secrecy. Regardless of whether the agreement is unilateral or mutual, information provided to USC under the agreement cannot be disclosed to a third party or may be limited to persons within USC on a need-to-know basis.

Access to confidential information must be limited to personnel who need the information to perform the study, work with patients or work with ancillary groups. The information should never be shared outside of USC and should only be shared with others at USC if they need to know the information, and if they are informed that the information is confidential. PIs and CRCs alike are responsible for protecting confidential information. Consult USC’s “Guide to Confidentiality” for further information. 

The sponsor will provide a draft CDA to the CRC, which he/she will submit through OnCore. Once submitted, a contract manager at the USC CTO will work directly with the sponsor to execute the agreement. Once the terms have been agreed upon, the PI will need to sign, as well as an authorized signatory authority for USC, and a representative from the sponsor. Once fully executed, the sponsor will send the protocol and related documents for review and the CRC will complete the feasibility questionnaire.

Finally, it is important to note that confidentiality requirements may also appear in a clause within a CTA, technology license, data sharing agreement, or material transfer agreement (MTA).

Industry-sponsored trials require a site qualification visit, also known as a pre-site selection visit, in which the sponsor or a Clinical Research Organization (CRO) visits USC to determine if the site is suitable for the study. During this visit, the equipment, facilities, pharmacy, staff, and patient population will be evaluated to determine whether or not the site can successfully conduct the trial and meet patient accrual goals set by the sponsor.

Contract and Budgeting Process Guidance Map

This guidance map below provides information about which office handles which aspects of the budgeting and contracting process based on two things: the study’s funding source and whether or not the study will use hospital resources such as clinic rooms, pathology, etc.

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1. Contracting Process 

For industry sponsored studies, the CTO supports PIs and research sponsors in the creation of CTAs that support development and testing of novel therapies, devices and diagnostics. 

The CTO’s operations have three main components: 1) contract review, negotiation, and execution; 2) coverage analysis; 3) budget development and negotiation. 

CTO uses OnCore, a clinical trials management system that allows study teams to maintain the protocol submission, study calendar, budget summary, participant tracking and invoicing, etc. CTO’s post-award team performs functions previously done by Sponsored Projects Accounting (SPA), as SPA is no longer involved in industry-sponsored studies. As of April 2016, all new clinical trials will be initiated in OnCore. Click here to see the memo from CTO regarding the OnCore Implementation plan. 

The CTO is divided into teams, each responsible for a number of departments. Each team includes a senior contract manager, budget specialist, and coverage analyst. Post-award accountants are assigned to various departments as well. 

CTO: To arrange for training or assistance with OnCore, complete the OnCore Training Request Form.
Email: OnCoreSupport@med.usc.edu or call 323-442-7218.
For a list of contacts at the CTO, click here.

The following bullet points outline the various types of agreements and illustrate the process for CTO’s most frequent activities, identifying the specific responsibilities of the study team versus the CTO staff:

Confidentiality Agreement

● The PI should initiate a CDA submission by submitting through OnCore
● After negotiation of CDA language, the PI should sign to indicate that he/she reads and understands the language (prior to signature by the CTO’s contract negotiator)
● Once CDA is executed, the PI and study team should ensure that information is kept confidential and only provided to people at USC on a “need to know” basis. Those who need to receive information should be given access to the minimum amount of confidential information necessary to effectuate the study, informed of its confidentiality, and informed that confidential information should never be shared outside of USC

Clinical Trial Agreement (Sponsored-initiated)

● The PI should initiate a clinical trial submission through OnCore
● In the submission, the PI should include the study protocol authored by sponsor, sponsor’s proposed Clinical Trial Agreement (CTA), lab manual(s) and sponsor’s proposed budget and informed consent in this submission. Additional essential documents include the protocol, Investigator Brochure, NCT # (for ClinicalTrials.gov), and CTU order form (as applicable)
● The PI and study team should respond to queries from budget specialist regarding budget parameters as first response to sponsor’s initial budget
● Once the CTO completes negotiation, the PI should approve the budget, including the final signature and approval by Department Chair or designee of Department Chair

Clinical Trial Agreement (For PI-initiated, industry-funded study)

● The PI should initiate a clinical trial submission through OnCore
● The PI should include the study protocol authored by the PI, sponsor’s proposed CTA, if available, and PI’s proposed budget
● The PI should respond to queries from budget specialist regarding budget parameters as required to cover the study costs
● Once the CTO completes negotiation, the PI should approve the budget, including the final signature and approval by Department Chair or designee of Department Chair

Medicare Coverage Analysis Process

● Coverage analysis occurs by the CTO automatically as soon as the OnCore submission is completed
● The PI should review and approve coverage analysis determination showing services and activities that will be paid by sponsor, insurer or other USC account 
● Once study is activated by CTO’s budget specialist in OnCore, the PI and study team agrees to conduct clinical trial in accordance with the CTA and approved protocol. At this time, the PI and study team should seek IRB approval 

Contract Review, Negotiation, and Execution

The CTA is the contract between the university and a sponsor. It outlines the obligations for each entity and defines the scope of work on a clinical trial. For example, a CTA will state contract terms associated with:

● The amount that USC will be reimbursed for work on a trial, and the conditions by which USC will be paid (e.g., startup costs and per-patient enrollment costs)
● Obligations to protect confidential information
● Rights of the sponsor to monitor the work at USC, and to inspect patient records
Liability in case something goes wrong in a trial
● Rights to intellectual property created prior to and during the trial
● Rights of the university to publish research that relies on data collected during the trial
● Study-related PI and USC obligations, including reporting of Adverse Events and other reports prepared pursuant to the study protocol
● Study period and procedures associated with early termination of the study

The CTO negotiates with the sponsor to ensure that the contract terms are reasonable and fair, while aiming to start trials and enroll patients as quickly as possible. The CTO senior contract manager is responsible for negotiating the non-financial terms of the CTA. The starting point for this work is typically a template agreement provided by USC—or more commonly, by the sponsor. In some cases, USC has negotiated a master agreement with a sponsor that pre-determines many of the terms and conditions, thus expediting negotiations. 

When a template comes from the sponsor, the proposed CTA includes the industry sponsors’ preferred contract terms. The CTO senior contract manager is responsible for reviewing these CTAs in order to identify terms and conditions that are inconsistent with governing federal regulatory policies and regulations (e.g. FDA, HIPAA privacy rules) and USC policies and regulations with respect to participants, such as dissemination of research results and management of potential intellectual properties developed during the performance of the study, in accordance with sponsor’s protocol. 

The CTO senior contract manager will focus on finding language that is acceptable to both USC and the industry sponsor. During this process, the CTO senior contract manager may consult with and receive input from the PI, USC Office of the General Counsel, USC Stevens Center for Innovation, and USC Department of Risk Management and Insurance, as needed. Upon finding mutually acceptable alternatives for all disputed terms (except the budget and payment schedule), the CTO senior contract manager will facilitate the development of a clean copy of the negotiated CTA that is ready for signatures, pending the completion of negotiations conducted by the budget specialist (i.e. the CTA budget and payment terms). 
The CTO’s practice is to negotiate budget and payment terms in parallel with other types of contract terms. In some cases, depending on the items in dispute, this means that the budget and payment negotiations may have been completed before or after the completion of the CTO senior contract manager’s work. In such instances, the clean copy of the negotiated CTA will be ready for signatures. 

Medicare Coverage Analysis (MCA)

On a clinical trial, some costs for patient care may be billed to an insurer, and some costs may be billed to the sponsor. However, it is inappropriate and unlawful to bill a particular cost (e.g., a lab test or procedure) to both the insurer and the sponsor, and certain costs may only be billed to the sponsor.
In 2000, the Centers for Medicare and Medicaid Services (CMS) issued a national coverage determination (NCD) for clinical trials that defined which costs are billable to Medicare. Under the NCD, Medicare will only pay for routine patient care costs, certain research costs, and costs due to complications associated with participation in qualifying clinical trials. USC follows these same standards for all insurers. It is essential for USC to do so because violations might subject the university to fines under the False Claims Act.
To meet its obligations under the NCD, CTO conducts an assessment called a Medicare Coverage Analysis (MCA) to determine which activities to be undertaken in connection with a clinical trial may appropriately billed to insurance and which must be billed to a research sponsor. Generally, the process for making this assessment is as follows:
● Initiate a clinical trial submission through OnCore
● Include the study protocol authored by the PI, sponsor’s proposed CTA, and Sponsor or PI’s proposed budget. All essential documents related to the clinical trial below need to be included:

  • The protocol
  • Investigational drug/device brochure
  • Draft CTA
  • Sponsor’s proposed draft budget
  • Laboratory manual
  • Investigational New Drug (IND)/Investigational Device Exemption (IDE) letter
  • VAC form for device studies
  • Names of research personnel involved in the study and hourly/administrative rates
  • Sponsor contact information
  • NCT number

● CTO reviews the protocol and sponsor’s budget and other related documents and assesses which costs associated with the trial are “routine patient care costs,” and which are not.
● The completed coverage analysis is used to develop a counter-proposal to the sponsor’s proposed draft budget. CTO then negotiates with the sponsor and finalizes the research agreement and associated budget.
● Once the budget is finalized, a Research Order Form (ROF) is generated that is used for ordering all tests and procedures identified in the study protocol. The ROF indicates which services should be billed to insurance or Medicare as applicable and which should be billed to a USC research account. If a service is not billable to insurance, it must be charged to a research account identified on the ROF. 

Coverage Analysis Process
While the senior contract manager is starting to review the CTA, the coverage analyst will simultaneously begin working on developing a study-specific Coverage Analysis that identifies and distinguishes any and all costs that must be charged to the sponsor (research-related) from those routine patient care costs that could be charged to private insurance or Medicare, as applicable. Coverage analysis is completed for all clinical research, whether it is sponsored by industry or not. 

Budgeting Process 
To start, the CTO budget specialist starts to build USC’s first response to the sponsor’s proposed budget after the coverage analysis is completed. The CTO budget specialist works with PIs, CRCs, department financial administrators, and representatives from other participating units to produce a comprehensive budget that will facilitate the process of negotiating the budget and payment terms with the sponsor. In addition to completed coverage analyses, the CTO budget specialist uses the study protocol, sponsor’s budget spreadsheet, informed consent, and contract payment terms to complete the development of USC’s first budget. USC’s first budget is then sent to the sponsor for their review and response. This is where the budget negotiations will begin, focusing on differences between USC and the sponsor’s budgets. 

Upon reaching an agreement with respect to the budget and the payment schedule, the CTO contract officer is charged with finalizing the entire clinical trial contracting process (assuming that the contract term negotiations are completed as well). This process includes collection of all the necessary documents (including a fully executed CTA with the final budget and payment schedule) and performance of all the required data entries and verifications in Database Management Systems such as iStar and OnCore. The CTO contract specialist will conduct a consistency check in which the specialist checks the language in the ICF against the terms of the contract to ensure consistency. Once the consistency check is complete, the stamped versions of the ICF will be released and iStar will send a letter to the study team notifying them that the study can begin. Once the signed CTA and other relevant documents are uploaded in OnCore and study is activated in OnCore, the post-award management of the clinical trial will start through activities such as creation of a financial account, initiation of invoicing/billing, and the conduct of necessary monitoring procedures.

Negotiation Delays and Hold Status
If the negotiations are delayed, the CTO may submit a “hold request” to the CTO Director. The CTO staff will then attempt to follow up to obtain the necessary information to complete any part of the process outlined in this sub-section. Study staff will be notified if the study is put on hold. If the hold is due to study team delays, it is their responsibility to provide the necessary information and submit an email request to the CTO project specialist or contract manager to remove the hold and resume negotiations. The CTO and the study staff monitor holds that are due to the sponsor’s delays, whereas just the study team monitors holds that are due to pending IRB approval. Once the information has been updated, the study that was previously on hold is reassigned and the study is treated as a new submission, so the timelines will reset.

The process is complete when the CTO has uploaded the final, executed documents onto OnCore (including the MCA, contract, budget, and ROF), and the award is forwarded to the Keck School of Medicine. After the appropriate documents are processed, the study can proceed to the next step, which involves IRB approvals.

USC CTO: 323-442-7218
Sara Katrdzhyan, Pre-Award Manager: Sara.Katrdzhyan@med.usc.edu  


1. USC Clinical Trials Unit (CTU)
The USC Clinical Trials Unit (CTU) provides the infrastructure, resources, and support to conduct human studies, with a focus on early phase and complex mechanistic trials. CTU can assist study teams with accommodating patient visits for high intensity trials that involve serial blood draws, infusions, and monitoring. The CTU also has trained clinical staff like research nurses, phlebotomists, radiology technicians, and more. The staff is highly experienced in collecting and processing PK and PD samples in a timely and efficient manner.

CTU: Yolanda Gutierrez, Assistant Director for Clinical Research Operations; 323-865-3056; cerda@med.usc.edu or ctu@sc-ctsi.org

The CTU also offers a specimen-processing center that offers a variety of services and serves as a one-stop unit for processing, storing, and shipping research samples collected from research patients. The USC CTU has the capability to provide X-ray absorptiometry (DEXA) for body composition or bone densitometry studies. The CTU also provides specimen collection and processing services that may include blood, saliva, sputum, urine, stool, hair follicles and other types of specimens. In addition, the CTU Processing Center can perform specialized processing for studies in which the assays are run in the investigator’s lab, research core lab, or sponsor’s central lab. Specimen processing may include the following: Serum/plasma separation, buffy coat separation, custom labeling, centrifuging, aliquoting, blood smear, PBMC separation; assistance with shipping & handling (ambient, refrigerated, dry ice). To learn about CTU’s full capabilities, click here.

CTU Laboratory: Lilit Baronikian, CTU Lab Supervisor, 323-865-3379 (office) or 818-642-4838 (cell), yegiyant@med.usc.edu

2. USC Investigational Drug Services (IDS) Pharmacy
IDS Pharmacy supports human studies involving investigational products and supports safety and care for research participants in both the inpatient and outpatient areas. IDS Pharmacy integrates its activities with the clinical, safety, informatics, administrative, and drug distribution systems of the hospitals and clinics to optimize investigational product therapy for patients. IDS Pharmacy assists with regulatory compliance, integrity of blinding and randomization, dispensing of investigational products, temperature monitoring, and more. 

Coordinating with the IDS Pharmacy early on is crucial to ensuring that they can accommodate requests for creating, storing, and dispensing the study drug, even during the site qualification phase. If the study requires the use of an investigational product, the PI will need to involve the IDS Pharmacy.

You should contact the IDS Pharmacy via e-mail as soon as you have identified that your study involves investigational product (ideally before IRB submission). They will respond within 1-2 business days and they will draft a scope of service agreement that details your study’s pharmacy fees depending on whether it is industry-sponsored, government-sponsored or investigator initiated.
  
It may be necessary to set up a site qualification visit. If so, the study team should inform them of the items to be assessed during the site qualification visit and work with them to prepare accordingly. The study team should provide additional information to the IDS Pharmacy that will help them determine how feasible it will be for them to take on the study. For example, providing information about the estimated number and size of the study kits or investigational drug that needs to be stored, how frequently they will be shipped, and how the drug will need to be dispensed and stored will be helpful to the IDS team. 

If on-campus pharmacies are unable to accommodate, it will become necessary to explore other options such as third-party pharmacies near HSC campus to see if they can assist with storing and dispensing the drug. There are local third-party compounding pharmacies that can assist with dispensing drugs, and other compounding pharmacies around the U.S. that can assist with creating drugs and placebos. Their fees will depend on the details of the study. 

IDS: PIs should contact the IDS Pharmacist (idspharmacy@med.usc.edu, 323-865-3538) to determine study feasibility and budget requirements. Depending on the protocol, pharmacy services may be conducted at the IDS Pharmacy or transferred to satellite sites (such as Keck Hospital of USC or Norris Cancer Hospital).

Other Pharmacies: For a list of possible pharmacy options beyond those at HSC, contact the SC CTSI CRS group at crs@sc-ctsi.org

3. Radiology & Imaging
Radiology and imaging services are available at the Norris Cancer Center and at Keck Hospital (Healthcare Consultation Center II and the PET Center in Healthcare Consultation Center I). Patients recruited from LAC+USC may be imaged at HCC2 or the PET center only if funding is available. The process can be initiated while the study is under review by the IRB. However, no research scans may be scheduled until the study has final IRB approval, which is contingent on RSC approval. In addition, research scans can’t be scheduled until ROF is available and Radiology Scan Request form (if applicable) is completed. Radiology research imaging charges are determined by the coverage analysis performed by the CTO. Please note there is a charge of $330 by the Department of Radiology for completion of RECIST tumor flow sheet form by a radiologist. Please make sure CTO is aware and prepares your budget accordingly.

Radiology: The coordinator will send an email to Bhushan Desai (bhushand@usc.edu; 323-865-9949) or contact the Department of Radiology at 323-442-8541, outlining the imaging requirements for the study and provide any additional materials (i.e., imaging manual). Imaging can be requested using the Research Order From created by the Clinical Trials Office. 

Imaging
Center for Image Acquisition
The Center for Imaging Acquisition, part of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute, houses MRI equipment used for neuroimaging. The Center has other equipment to help PIs conduct scans that ensure the comfort for participants. Click here for a full list of equipment and capabilities. 
CRCs can schedule appointments with the Center by creating an account under the “For Investigators” tab. The following information will be needed for the application: project name, proposal number, PI name, anticipated start date, copy of IRB approval letter, copy of study budget showing scan costs. Once the application is approved, login credentials will be provided, and users will be able to schedule online. Investigators preparing budgets for new proposals should contact the center to obtain the latest rates for scans and other services. Please allow at least 2 weeks for rate requests to be approved. 

CIA: Direct any questions to CIA@ini.usc.edu.

Molecular Imaging Center – Radiochemistry/Cyclotron Labs
The Molecular Imaging Center (MIC) is a comprehensive imaging program focused on the development of various types of PET tracers used for imaging disease. The facility includes a Cyclotron GMP facility, PET radiochemistry laboratories, access to small animal imaging, and access to clinical PET/CT imaging facilities. 

PIs interested in utilizing these services should contact Peter S. Conti, MD, PhD to set up an initial meeting to discuss the feasibility of the study, the radiotracer availability/preparation and clinical trial enrollment. Clinical imaging studies will be performed under pre-IND, IND, or approved drug protocols at HCC-I. Opportunities for early-phase clinical trials and multi-center trials are available at MIC including existing trials in the following areas:

Oncology:
● Breast Cancer
● Prostate Cancer

Neurodegenerative Disease:
● Alzheimer’s Disease
● Parkinson’s Disease

Cardiovascular Disease:
● Cardiac Ischemia

4. Pathology
The point of entry for all human biospecimen procurement needs is the Translational Pathology Core Facility (TPCF) of the USC/Norris Comprehensive Cancer Center, including whether for clinical trials, non‐interventional translational research studies, basic research studies, and whether cancer‐related or not. In this capacity, the TPCF works closely with the hospital‐based employees of the LAC+USC Medical Center and the Keck Medical Center to facilitate the process of research tissue acquisition and processing and to insure compliance with federal, state, and local hospital regulations. The activities of the TPCF are supported by chargebacks to the study PI. Any investigator may request services from the TPCF, and Cancer Center members receive services at a discounted rate. Specimens can be obtained by USC investigators with IRB approved, funded studies with a valid Lab Agreement.

For all research studies requiring the use of human biospecimens, including both clinical trials and non‐interventional (non‐clinical trial) translational research and basic research studies, investigators must submit the Laboratory Agreement Request Form in order to obtain approval to procure biospecimens. The laboratory Agreement Request Form must only be submitted after funding and IRB approval have been obtained. Once the Lab Agreement is approved, the investigator will meet with Pathology to arrange the implementation of the biospecimen procurement, processing, and distribution required by the protocol. 

For clinical trials, once the trial is opened, two additional forms will enable investigators to request procurement from individual patients: Request for Formalin Fixed Paraffin Embedded (FFPE) Slides/Tissue Blocks and/or Request for Fresh/Frozen Tissues can be obtained from and submitted to Ms. Chen. 

Types of human biospecimens available for research: 
1) Formalin-fixed, paraffin-embedded (FFPE) tissues: 
All tissues taken during the course of clinical care are saved for a period of time in the hospital archives in the form of FFPE blocks. These can be used for research purposes provided appropriate consent and IRB approval have been obtained. At Keck Medical Center, these tissues are stored indefinitely. At LAC+USC, the FFPE tissues are stored in the hospital archives for 10 years, at which point they are donated to the Population Based Tissue Arm of the TPCF (Wendy Cozen, DO, director). TPCF personnel can assist with procurement and sampling (e.g., sectioning, coring) of FFPE blocks in the hospital archives. 
2) Fresh, fresh/frozen, and fluid specimens (e.g., whole blood, serum, plasma, buffy coat, and urine):
Fresh, fresh/frozen and fluid biospecimens can be collected prospectively for IRB approved, funded studies with a valid Lab Agreement and patient Informed Consent. Typically both tumor and matched normal tissue are collected immediately after explanation under the supervision of the service pathologist/PA. The TPCF personnel will assist with the immediate processing and storage of the specimens, banking, tracking, distribution, and processing of specimens required for analysis.
 

5. IRB Application Submission and Approvals Process 
In order to initiate the IRB application submission process, the study application and protocol will need to be submitted to iStar. All co-PIs must agree to participate in the study before the PI can submit the application to the IRB for review. Ultimately, the application needs to be approved by the PI or co-PI in order to finalize submission, after which the Division/Departmental must approve the application in order to route the study for IRB. IRB staff are then assigned to conduct a cursory review. 

All investigator-initiated non-cancer clinical trials that have not undergone prior scientific review by a qualified scientific body are automatically routed to the SC CTSI Clinical Research Support Scientific Protocol Review Committee to undergo scientific and feasibility review as a part of the IRB review process. More information regarding the Scientific Review process can be found in Section V. IRB Approvals Process, subsection E.

After scientific review is complete or not deemed necessary, the IRB administrator categorizes the study as Full Board, Expedited, or Exempt. If the study is subject to Full Board Review, as is true for most clinical trials, the study will be assigned to a Committee Review. During the Committee Review Process, the board members will conduct independent reviews, followed by a Committee Meeting during which the study protocol and corresponding risks are discussed.

Process.png#asset:6739

If the IRB has questions or issues with the protocol, contingencies will be given to the PI and study team. A contingency is an item from the IRB that must be addressed in the next submission before the IRB can approve the study. When responding to the IRB, it is best to err on the side of caution and explain the decision making and study processes in more detail rather than less so that the analyst and/or board can understand the rationale without having to ask for clarifications from the PI and study staff. Once all contingencies have been adequately addressed, the IRB will approve the protocol within iStar. The approval comes in the form of an IRB approval letter uploaded to iStar that outlines what was approved. However, it is important to note that IRB approval does not necessarily mean that the study can begin, especially in the case of industry-sponsored trials. Once the contract is finalized, the IRB will re-issue an approval, indicating that the study can begin. At this time, the IRB will also release the approved and stamped ICFs.

Upon release, the IRB approval letter and ICF is approved for one year for one year from the release date. If the study plans to continue past one year, continuing review must be completed. More information about continuing review is found in the Appendix. If the study closes after one year, more information about that process is also found in the Appendix. More information on the USC IRB and the Office for the Protection of Research Subjects (OPRS) can be found here.

6. Site Initiation Visit for Industry-Sponsored Studies
Once the PI has executed the CDA on OnCore, received the study synopsis, and USC has been selected as a site, the sponsor will send over the regulatory packet and contract, as well as the budget templates. The PI and staff will upload the essential documents and templates into OnCore, submit to the IRB (see Section V for more information), and start building the initial budget in discussion with the sponsor. 

Once the contract is fully executed or likely to be full executed, the PI and staff will schedule the Site Initiation Visit (SIV). (The industry study representative, usually the CRA or Monitor, will need to register via Intellicentrics and ensure to follow all USC visitor protocols while on site.) The purpose of an SIV is to have the PI, site study staff and sponsor meet to discuss the study, have the sponsor train the study staff on the protocol, and discuss the roles of the PI and team members and the delegation of study-related tasks. Toward the end of the SIV, the involves parties will complete the Delegation Log, and the sponsor staff will ask if there are any questions before the SIV training log is completed. The CRC should keep a copy of the training log for study records.

Additionally, if a device will be used as part of the study, the PI and staff will submit a Value Analysis Committee (VAC) form to the hospital. The VAC form is necessary if the PI is planning to use the device in any of the Keck hospitals or affiliated clinics. Whether or not the PI or department plans to purchase the device or receive it at no charge, they will need to complete a Purchasing Order Form, which will be processed through the CTO. More information about the VAC process is included in the section titled, “Approvals Process for Using Devices within Keck Hospital.” 


Section IV. Study Lifecycle: Planning/Pre-Submission

As part of the study start up process, PIs and research staff will need to gain access to relevant USC systems that will allow them to carry out necessary tasks involved in clinical research conduct. These systems include OnCore, Kuali Coeus (KC), iStar, REDCap, and more. Some systems can/will be used for all clinical research studies regardless of their funding source, such as iStar and OnCore, whereas some will be used only if a study is funded by a specific source. 

Users must have a USC email address before accessing these systems, and some require Shibboleth or Duo authentication to access. The links below provide information about each system. For setting up access to these systems, contact the appropriate help desk:

OnCore: OnCoreSupport@med.usc.edu or call 323-442-7218
Kuali Coeus: Departmental finance managers should be able to assist PIs and study personnel with access and troubleshooting KC
iStar: istar@usc.edu or call 323-276-2238
REDCap: For information on how to obtain a REDCap account, click here. support@sc-ctsi.org or call 323-442-0217
Sophia: Click here to access Sophia
DiSClose: Click here to access diSClose
CITI: citi@usc.edu or call 213-821-5272
ClinicalTrials.gov: Click here for info on how to register a study
USC eMarket: Click here for access information

Setting up a USC Email Account
Access to relevant online systems at USC (including iStar, OnCore, and others) requires set up of a USC net ID account and obtaining a USC email address ending in @med.usc.edu or @usc.edu, depending on the home department. During the onboarding process, department HR managers will assist with the set up of these accounts. 

For issues with USC email, contact the Keck IT Helpdesk at 323-442-4444 or helpdesk@med.usc.edu. For issues with the net ID, contact the USC Helpdesk by phone 24 hours a day, 7 days a week at 213-740-5555 or consult@usc.edu.

During the planning stages of an investigator-initiated study, prior to submitting a protocol to the IRB, a PI starts out with an idea for a research study. She will consider who will fund the study; how the study should be designed, statistically analyzed, and operationalized; what type of equipment is needed; how many participants she is looking to recruit over what length of time; and more. She will think about her study team and perhaps recruit personnel to join her staff, as well as any necessary trainings they should complete. 

When an idea is in this phase, a PI should begin by obtaining a biostatistics consultation. Biostatisticians can assist with protocol design, statistical planning, feasibility analysis, and more. USC investigators have two options for biostatistics help, depending on the nature of the support needed and the PI’s affiliation. The Norris Cancer Center Biostatistics Core focuses on cancer studies for members of the Norris Comprehensive Cancer Center. 
SC CTSI BERD typically focuses on short-term statistical collaborations across the lifespan of a study. However, they also offer a longer-term solution to the need for statistical assistance in the form of a biostatistician whose time can be contracted on an effort-based basis. 
Details about each option available at Norris and SC CTSI, as well as other opportunities for statistical consultation, are provided below.  
a. Norris: Contact the Norris Cancer Center’s Clinical Investigations Support Office (CISO) at 323-865-0463 or CoreCISO@med.usc.edu to schedule a feasibility meeting for the proposed clinical trial or study with representatives from all the relevant cores. There is no charge to Cancer Center members for Biostatistics Core support.  However, Cancer Center members are fully expected to include statistical faculty and staff on grant application budgets and on contracts.  
b. SC CTSI BERD: Fee-for-service rates: $125/hour after initial free consultation up to one hour. For some investigators, CTSI provides a subsidy of extra support, indicated below. The only way BERD will process requests for assistance is through completion of their online service request form.

If the PI is…

He/she is eligible for additional free support per year in this amount:

Junior investigator

Up to 5 hours/project

(3 projects max per year, so 15 hours annually)

SC CTSI Pilot Funding Awardee

Up to 2 hours per project

K Scholar

Up to 15 hours annually, only while they are in their K-funded period

T Trainee

Up to 15 hours annually, only while they are in their T-funded period

Working on extramural grant planning

Up to 3 hours per grant

PM516 Volunteer

Up to 5 hours

Clinical research informatics and bioinformatics resources can assist PIs with the research process by streamlining the study planning process, helping with feasibility assessments using local patient counts, and more. 

SC CTSI Clinical Research Informatics (CRI) core provides various tools to assist with cohort discovery, to explore available patient populations across Keck, DHS, and other hospitals in Los Angeles. One such tool includes i2b2, a tool that allows study teams to plan human studies by searching Keck, DHS, and CHLA patient records. Study teams can obtain de-identified, aggregate, and identified patient databases with IRB approval. 

Another tool is TriNetX, which includes data from i2b2 but contains many more features which allow users to visualize data in more appealing ways. Users wanting to use i2b2 or TriNetX will need to request an account from CRI.

Please note that in order to release identified patient data, the PI and study team must obtain IRB approval for each specific piece of data they would like to request. For example, if the team is requesting patient name, address, phone number and email address, they must explicitly request this in their IRB amendment and it must be approved by USC IRB before the Informatics team can pull and release the identifiable, patient-level data to the PI and team. 

Norris Bioinformatics core offers a range of services to researchers across the Cancer Center at USC and other academic institutions on a fee-based or combination of fee- and collaboration-based service. Services include in-silico (computational) bioinformatics-based analysis to basic, clinical, and translational research applications.

Another tool, called the Los Angeles Data Resource (LADR) Cohort Discovery System, is a joint project between USC, CHLA, UCLA, City of Hope, and Cedars-Sinai. LADR allows PIs to search for the number of patients meeting their proposed inclusion/exclusion criteria across these five hospitals.
 
The Cancer Research Informatics Core (CRIC) develops and supports databases for laboratory data management, multi-center clinical trials coordination, epidemiologic & prevention studies as well as disease specific studies. Equipment and services include tools for data collection, migration and reporting, customized survey creation, and web-based data capture & reporting.

Norris Library provides bioinformatics support including statistical analysis of high-throughput data and DNA/protein sequence analysis, comprehensive functional analysis and advanced literature and data search and mining, as well as workshops and training of available software tools.

CRI: To obtain an account or get training, email the support team at i2b2@usc.edu or call 323-442-0217.

Before undertaking any study, the PI and study team must determine the feasibility of conducting the study at their institution. This involves (but is not limited to) assessment of the following factors:

● proposed study budget and availability of local resources
● ability to recruit the necessary number of participants who meet the inclusion criteria
● the research team’s effort or time
● availability of the PI to oversee study conduct
● sufficient funding to run the study and compensate participants
● pool of eligible participants
PIs can use cohort identification tools such as i2b2 to assess feasibility at USC. The “Clinical Research Informatics Resources” section contains more information about cohort identification tools.

When assessing the availability of resources required to successfully carry out an IIT or sponsored trial, a PI may realize he doesn’t have adequate space to carry out the study.

1. The USC Clinical Trials Unit (CTU) specializes in medium to high-complexity human studies that involve serial blood draws (i.e. PK & PD). The CTU provides for-fee space (located in the Breast Center in HC4) for conducting study visits, as well as qualified research personnel such as research nurses, phlebotomists, and lab technicians. 

CTU: Yolanda Gutierrez, Assistant Director for Clinical Research Operations, cerda@med.usc.edu, 323-865-3056 or ctu@sc-ctsi.org

2. The Diabetes & Obesity Research Unit (DORI) located in the Clinical Sciences Center also provides space and services to conduct research, such as nursing and phlebotomy services, patient rooms, and metabolic tests such as DEXA scans.

DORI: Christina Ayala, MPH, Project Manager, trujillc@usc.edu, 323-442-2500. 

In order to work with human participants and protected health information, all research personnel must be appropriately trained and certified. These certifications should be kept up-to-date before they expire in order to ensure compliance. 

The USC Office of Research hosts several online trainings on a variety of topics. These trainings can be accessed through the Research Training Finder. Users can filter trainings based on role (administrative staff, faculty/PI, research coordinator, and more) as well as their responsibilities (managing contracts and grants, shipping biological materials, handling human tissue, etc). In addition, USC offers training through the CITI program as well as access to modules provided by the Association of Clinical Research Professionals (ACRP). Your department administrator should have the login and password to access these ACRP trainings. For any questions about ACRP training and login access, contact Clinical Research Support at crs@sc-ctsi.org

For research administrators and support staff who work in contract and grant development, a relevant training includes a 12-course online module called “the Cardinal and Gold Curriculum.” A Grants Management Training Program for PIs also can be accessed from the Office of Research website.

The USC Environmental Health & Safety (EHS) department hosts multiple in-person trainings for research staff working with a variety of devices and substances. For example, if you have the potential to be exposed to bloodborne pathogens, you’ll need to attend the bloodborne pathogens training. If you’ll be responsible for shipping and handling biological materials, you’ll need to attend the training on shipment of biological materials and/or dry ice. These trainings are held multiple times per month virtually via Zoom. Registration is required and can be completed online at this website. To better understand what trainings you should obtain based on your responsibilities, use this guide sheet. If you have any questions, email EHS at ehs@usc.edu or call them at 323-442-2200.

Finally, the Regulatory Knowledge and Support (RKS) group at SC CTSI has a training module for how to ensure clinical trial quality and how to monitor a study that can be accessed here. They also have other educational offerings, training resources and videos from their previous boot camps/symposia here.

For an overview of required trainings for new or junior investigators, see the figure below, also found at the beginning of this section of the Guide To Clinical Research.

Investigators-quick-guide.jpg#asset:6727Investigators-quick-guide-2.jpg#asset:6728

During the training phase, a PI may also realize he does not have adequate staff effort to dedicate to the conduct of the project or trial. Some departments have their own pool of dedicated study staff, such as research coordinators, research nurses and project assistants. If you are unsure whether your department has such resources available, consult with your department administrator. 

If your department does not have dedicated study staff, there are options to hire staff through the SC CTSI Clinical Research Support group, and the Clinical Trials Unit.

Study coordinators are available for hire through the SC CTSI’s clinical research coordinator pool. These CRCs are highly trained, familiar with the process of conducting research at USC, Keck, and LAC+USC, and can be available for short or long-term project needs. They can assist on any type of clinical research including IITs, non-industry funded, and/or industry-funded studies. Most CRCs are bilingual and fluent in Spanish, and many are phlebotomy-certified. These skills can be requested by the PI if needed and are based on availability. If you are interested in obtaining more information about hiring a CRC, contact the Clinical Research Support Research Coordinator Supervisor Lily Jara or 626-483-7876.

Research nurses are available for studies utilizing the USC Clinical Trials Unit (CTU). CTU provides the infrastructure, resources, and support to conduct human studies – such as space for physical examinations, infusions, biopsy procedures, laboratory and processing of bio-specimens, nursing and phlebotomy services, and more. To obtain more information about the CTU, including cost, contact the Assistant Director for Clinical Operations Yolanda Gutierrez or 323-865-3056.

Finally, ensuring your staff members are properly trained and delegated to perform the tasks associated with the study is a necessary part of the planning process. Researchers who propose or conduct research sponsored by the Department of Health and Human Services (i.e. NIH, CDC, AHRQ, HRSA) must complete conflict of interest in research training every four years. For more information about necessary human subject-related trainings, see the Investigators’ Quick Guide to Getting Started in Clinical Research at USC on page 14-15.

Any PI or research staff conducting research within a Keck Medical Center of USC facility – including hospitals and ambulatory locations – must be credentialed to access and work in that facility.

Contacts by location
Keck Medical Center of USC:
CRCs and any non-physician research associates must be credentialed in order to perform study-related activities at Keck and any of its affiliates including Norris, Verdugo, and associated clinics. The credentialing paperwork involves the completion of forms and submission of documents including picture ID, license/certificates, professional liability insurance, CV, health clearance documents, questionnaire and more. Be advised that this approvals process can take between 2-3 months. 

Any questions about necessary credentials and clinician privileges should be directed to Ellen Whalen, Associate Administrator Academic Affairs; Ellen.Whalen@med.usc.edu. The phone number for the Office of Integrated Credentialing is 323-442-6820.

To gain access to hospital facilities including freezer spaces and operating rooms, research personnel must contact the HR manager for their department as well as HSC Facilities: Ana Orvieto; Ana.Ortega@med.usc.edu

LAC+USC Medical Center: Employees of USC/Keck who also need access to LAC+USC Medical Center facilities will be onboarded as contracted employees through a departmental sponsor at LAC. The HR manager for your department should be able to refer you to the appropriate sponsor contact at LAC. The onboarding process involves completing a health clearance and background check before a badge can be obtained. The health clearance process involves providing copies of your immunization forms, and proof of a negative TB test taken within the last six months. Copies of these documents should be brought to the Employee Health desk located at the first-floor office in the IRD building at LAC+USC or emailed to the contact designated by your department’s HR manager.

LAC+USC HR: 323-409-2300; lacuschr@dhs.lacounty.gov

Coordinating ancillary services early on is crucial to ensuring there are minimal delays in the study preparation process. Relevant ancillary services include radiology & imaging, pharmacy, pathology, cardiology, and ophthalmology. There are over 60 research laboratories and services located at UPC, HSC, and CHLA, offering researchers access to state-of-the-art facilities, technologies, resources and expertise across academic disciplines and clinical specialties. Researchers can use the link above to segment searches for labs and services based on location or research area.

The following section provides a description of the services provided, how to request the service, and contact info. 

1. USC Medical Plaza Pharmacy
There is another pharmacy, in addition to IDS pharmacy, located on the HSC campus. The Plaza Pharmacy is located in HC2 and can assist with filling prescriptions and dispensing drugs for studies on a limited basis. PIs should discuss needs early on to see if Plaza can accommodate the study drug.

Plaza Pharmacy: Contact Rena Charchian; Director of the Plaza Pharmacy; 323-442-5770

2. Radiology
Radiology and imaging services are available at the Norris Cancer Center and at Keck Hospital (Healthcare Consultation Center II and the PET Center in Healthcare Consultation Center I). Patients recruited from LAC+USC may be imaged at HCC2 or the PET center only if funding is available. The process can be initiated while the study is under review by the IRB. However, no research scans may be scheduled until the study has final IRB approval, which is contingent on RSC approval. In addition, research scans can’t be scheduled until ROF is available and Radiology Scan Request form (if applicable) is completed. Radiology research imaging charges are determined by the coverage analysis performed by the CTO. Please note there is a charge by the Department of Radiology for completion of RECIST tumor flow sheet form by a radiologist. Please make sure CTO is aware and prepares your budget accordingly.

Radiology: The coordinator will send an email to Bhushan Desai (bhushand@usc.edu; 323-865-9949) or contact the Department of Radiology at 323-442-8541, outlining the imaging requirements for the study and provide any additional materials (i.e., imaging manual). Imaging can be requested using the Research Order From created by the Clinical Trials Office. 

3. Imaging
i. Center for Image Acquisition
The Center for Image Acquisition, part of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute, houses MRI equipment used for neuroimaging. The Center has other equipment to help PIs conduct scans that ensure the comfort for participants. Click here for a full list of equipment and capabilities. 

CRCs can schedule appointments with the Center by creating an account under the “For Investigators” tab. The following information will be needed for the application: project name, proposal number, PI name, anticipated start date, copy of IRB approval letter, copy of study budget showing scan costs. Once the application is approved, login credentials will be provided, and users will be able to schedule online. Investigators preparing budgets for new proposals should contact the center to obtain the latest rates for scans and other services. Please allow at least 2 weeks for rate requests to be approved. 

CIA: Direct any questions to CIA@ini.usc.edu.

ii. Molecular Imaging Center – Radiochemistry/Cyclotron Labs
The Molecular Imaging Center (MIC) is a comprehensive imaging program focused on the development of various types of PET tracers used for imaging disease. The facility includes a Cyclotron GMP facility, PET radiochemistry laboratories, access to small animal imaging, and access to clinical PET/CT imaging facilities.
PIs interested in utilizing these services should contact Peter S. Conti, MD, PhD to set up an initial meeting to discuss the feasibility of the study, the radiotracer availability/preparation and clinical trial enrollment. Clinical imaging studies will be performed under pre-IND, IND, or approved drug protocols at HCC-I. Opportunities for early-phase clinical trials and multi-center trials are available at MIC including existing trials in the following areas:

Oncology:
● Breast Cancer
● Prostate Cancer

Neurodegenerative Disease:
● Alzheimer’s Disease
● Parkinson’s Disease

Cardiovascular Disease:
● Cardiac Ischemia

MIC: Peter S. Conti, MD, PhD. 323-442-3858 / peter.conti@med.usc.edu and copy miclab@usc.edu.

4. Cardiology & CardioVascular Thoracic Institute 
Echocardiography services are available at the CardioVascular Thoracic Institute (CVTI), Keck Hospital of USC, and LAC+USC Medical Center. The Echo Core Lab can accommodate orders that are more complex.

The CVTI can accommodate outpatient research-related cardiovascular tests such as echocardiograms, electrocardiograms, or vascular ultrasound. As part of each trial, the CTO will develop a standard ROF that includes an echocardiogram request. That form should be submitted to CVTI at the time of research echo request. 

For inpatient researcg, echocardiograms can be ordered through Cerner like a regular echocardiogram. In the comments section for the order, input "research" and specify which study so that techs know how to modify echo as needed. If the study would be done for clinical purposes and is not being done for research purposes only, the comment is not necessary.

If the study calls for a regular echo, then staff will do a regular echo. If more complex echos are needed, details will need to be provided in order to educate staff in advance.  
How to request service: The PI or study team should contact one of the individuals listed below during the planning process in collaboration with IRB and CTO. The PI or study team will provide protocol, examination details and proposed CPT codes related to the type of echocardiogram needed to fulfill the study and budgetary requirements. The study team should ensure that CTO budgets adequately for the echocardiogram and develops an appropriate research order form. Information on expenses can be accessed via the USC CTO.

The same process for incorporating research echocardiograms into the budget and research order forms applies to studies performed at LAC+USC Medical Center. The PI and study team should be aware that properly budgeted research echocardiograms can be performed at CVTI or Keck Hospital as long as a research order form is completed. If the echocardiograms must be performed at LAC+USC Medical Center and will require a large number of studies on a regular basis, please contact CRU to discuss.
If an inpatient echocardiogram is ordered for research purposes, it will usually be done like any other inpatient echocardiogram. If the echo is urgent (i.e., must be done within 24 hours), then a phone call should be made to the echo lab to make sure it gets done when needed.

CVTI: Clinic Manager Elizabeth Vela elizabeth.vela@med.usc.edu. Click here for additional CVTI staff and faculty contact information.

i. Echo Core Lab
In addition to the standard echo orders and reads, another option for cardiology services is the Echo Core Lab. This resource is available for researchers who require echo reads that require measurements that are particularly complex and outside of the standard echo report. The Echo Core lab is experienced in reading echos for large multicenter trials to ensure standardization and quality. They are available to serve as the echo core lab for IITs and industry sponsored trials conducted at USC.

How to request service: Click here for additional contact information for USC Cardiovascular Medicine

CRU: USC Cardiovascular Research Unit (CRU)
323-442-6863 / fax: 323-442-7610
cru@med.usc.edu.

5. Ophthalmology
The Ophthalmology Clinical Trials Unit at the USC Roski Eye Institute conduct a wide range of clinical trials through a variety of subspecialty services, providing comprehensive ophthalmic exams and diagnostics. Subspecialties include: Cornea and External Diseases, Glaucoma, Oculo-facial Plastic Surgery, Neuro-Ophthalmology, Ocular Oncology, Uveitis and Ocular Inflammation, Retina, Vitreous, and Macular Diseases.

Each ophthalmic examination conducted by the Ophthalmology services will include a broad spectrum of ophthalmic evaluations. The exams may vary depending on the specifics of each clinical trial. A typical exam may include the following: Patient history, visual acuity, depth perception, color vision, eye muscle movements, peripheral vision, pupil response, refraction, tonometry (eye pressure), external examination (cornea, eyelids, conjunctiva), retinal examination/funduscopy (retina, optic disk, macula). The USC Roski Eye Institute offers the most advanced diagnostic technologies through their on-site services. For more information about the wide-range of diagnostic testing that may be conducted in each clinical trial, see below.

How to request services: Ophthalmology service for clinical trials may be accessed through the following procedure:
1. The requesting department PI or CRC should initiate contact with the ophthalmology clinical trial unit by calling 323-865-6935 or by completing our online contact form. For more information on ophthalmic clinical trials click here.
2. The scope of the trial and needed services should be presented through a Research Order Form (ROF), schedule of visits, and instructional documentation related to the requested services.
3. Charges should be obtained through the ophthalmology charge master on file with the CTO.
4. A full review by the ophthalmology PI and ophthalmology clinical trial unit will be conducted with feedback on available resources and clinical registration procedures.
Click here for contact information for the Department of Ophthalmology.

Ophthalmology CTU:
323-442-6335 / fax 323-442-6496
Yoon Hee Kim, Research Coordinator Supervisor Yoonhee.Kim@med.usc.edu.

6. Neurodiagnostic Department of USC Comprehensive Epilepsy Center
The USC Comprehensive Epilepsy Center is designated as a level 4 epilepsy center, indicating that the center and its associated staff can provide care for the most complex cases. The Neurodiagnostic Department can provide services such as electroencephalography (EEG). Specifically, routine, sleep-deprived or video EEGs are available for the purposes of diagnosing epilepsy or brain abnormalities. For more information and to coordinate services, reach out to the department directly.

Neurodiagnostic Department:
https://epilepsy.keckmedicine....

7. USC Sleep Disorders Center
The USC Sleep Disorders Center provides inpatient and outpatient sleep disorder evaluations. In addition to providing treatment for a variety of sleep disorders, the center also can be used as a location to conduct sleep assessments as part of a research study. The center includes a four-bed sleep lab and is staffed by board-certified sleep specialists and registered polysomnography technologists. For more information and to coordinate services, reach out to the center directly.

Sleep Disorders Center: sleepcenter@med.usc.edu

8. Pulmonary Diagnostic Services Lab
The Pulmonary Diagnostic Services Lab provides assessments that test pulmonary function, such as lung function evaluation, supplemental oxygen evaluation and bronchospasms evaluation. For more information and to coordinate services, reach out to the lab directly.

Pulmonary Diagnostic Services Lab: KeckPFTLab@med.usc.edu  

9. Dermatology
The providers at USC Dermatology possess clinical expertise in the management of rare and common skin diseases like psoriasis, atopic dermatitis, skin cancer, infectious diseases, autoimmune diseases and immunobullous diseases. Clinical dermatologic services that pertain to research patients can include skin biopsies, cyst removal and Mohs surgery. For more information and to coordinate services, reach out to the department directly.

Dermatology: dermatology@med.usc.edu

10. USC Clinical Trials Unit 
The Clinical Trials Unit at USC (CTU) provides the infrastructure, resources, and support to conduct human studies, with a focus on early phase and complex mechanistic trials. CTU can assist study teams with accommodating patient visits for high intensity trials that involve serial blood draws, infusions, and monitoring. The CTU also has trained clinical staff like research nurses, phlebotomists, radiology technicians, and more. The staff is highly experienced in collecting and processing PK and PD samples in a timely and efficient manner.

CTU: Yolanda Gutierrez, Assistant Director for Clinical Research Operations; 323-865-3056; cerda@med.usc.edu or ctu@sc-ctsi.org

The CTU also offers a specimen-processing center that offers a variety of services and serves as a one-stop unit for processing, storing, and shipping research samples collected from research patients. The USC CTU has the capability to provide X-ray absorptiometry (DEXA) for body composition or bone densitometry studies. The CTU also provides specimen collection and processing services that may include: blood, saliva, sputum, urine, stool, hair follicles and other types of specimens. In addition, the CTU Processing Center can perform specialized processing for studies in which the assays are run in the investigator’s lab, research core lab, or sponsor’s central lab. Specimen processing may include the following: Serum/plasma separation, buffy coat separation, custom labeling, centrifuging, aliquoting, blood smear, PBMC separation; assistance with shipping & handling (ambient, refrigerated, dry ice). To learn about CTU’s full capabilities, click here.

CTU Laboratory: Lilit Baronikian, CTU Lab Supervisor, 323-865-3379 (office) or 818-642-4838 (cell), yegiyant@med.usc.edu

11. Diabetes & Obesity Research Institute
The USC Diabetes & Obesity Research Institute (DORI) is a multi-disciplinary collaborative of investigators seeking to link basic, clinical, and public health research to advance the understanding of obesity and its relationship to type II diabetes. DORI operates a clinical research facility in the Clinical Sciences Center that supports outpatient studies of low to moderate intensity, such as interviews, medical histories and physical exams, single and multiple blood draws, and oral glucose tolerance tests. Protocols require participation by study teams; additional research nursing and phlebotomy assistance is available through DORI. Special capabilities include dual energy X-ray absorptiometry (DEXA) for body composition or bone densitometry studies performed by an experienced DEXA technician and a core lab that can be used by study teams to perform sample processing following training and approval by DORI staff members, and a metabolic kitchen and gym for nutritional and exercise interventions and assessments. DORI also has a Nutrition Data System for Research (NDSR) program that is used for dietary analysis and available to share with other PIs. Facilities and services are provided at a cost to PIs and their study teams. 

DORI: Christina Ayala, DORI Project Manager, trujillc@usc.edu, 323-442-2500.

Research facilities and core laboratories at HSC support research conduct through services in areas like high performance computing, genomics, cellular and molecular analysis, biomedical imaging, nanoscience, and data analysis and management. Core laboratories offer shared-use research facilities and provide technological support for research projects carried out by faculty across academic disciplines and clinical specialties. 

1. Pathology
The point of entry for all human biospecimen procurement needs is the Translational Pathology Core Facility (TPCF) of the USC/Norris Comprehensive Cancer Center, including whether for clinical trials, non‐interventional translational research studies, basic research studies, and whether cancer‐related or not. In this capacity, the TPCF works closely with the hospital‐based employees of the LAC+USC Medical Center and the Keck Medical Center to facilitate the process of research tissue acquisition and processing and to insure compliance with federal, state, and local hospital regulations. The activities of the TPCF are supported by chargebacks to the study PI. Any investigator may request services from the TPCF, and Cancer Center members receive services at a discounted rate. Specimens can be obtained by USC investigators with IRB approved, funded studies with a valid Lab Agreement.

For all research studies requiring the use of human biospecimens, including both clinical trials and non‐interventional (non‐clinical trial) translational research and basic research studies, after funding and IRB approval have been obtained, investigators must submit one form (the Laboratory Agreement Request Form) in order to obtain approval to procure biospecimens. Once the Lab Agreement is approved, the investigator will meet with Pathology to arrange the implementation of the biospecimen procurement, processing, and distribution required by the protocol. 

For clinical trials, once the trial is opened, two additional forms will enable investigators to request procurement from individual patients: Request for Formalin Fixed Paraffin Embeded (FFPE) Slides/Tissue Blocks and/or Request for Fresh/Frozen Tissues can be obtained from and submitted to Ms. Chen. 

Types of human biospecimens available for research: 
1) Formalin-fixed, paraffin-embedded (FFPE) tissues: 
All tissues taken during clinical care are saved for a period of time in the hospital archives in the form of FFPE blocks. These can be used for research purposes provided appropriate consent and IRB approval have been obtained. At Keck Medical Center, these tissues are stored indefinitely. At LAC+USC, the FFPE tissues are stored in the hospital archives for 10 years, at which point they are donated to the Population Based Tissue Arm of the TPCF (Wendy Cozen, DO, director). TPCF personnel can assist with procurement and sampling (e.g., sectioning, coring) of FFPE blocks in the hospital archives. 
2) Fresh, fresh/frozen, and fluid specimens (e.g., whole blood, serum, plasma, buffy coat, and urine):
Fresh, fresh/frozen and fluid biospecimens can be collected prospectively for IRB approved, funded studies with a valid Lab Agreement and patient Informed Consent. Typically both tumor and matched normal tissue are collected immediately after explanation under the supervision of the service pathologist/PA. The TPCF personnel will assist with the immediate processing and storage of the specimens, banking, tracking, distribution, and processing of specimens required for analysis.

Pathology: List of contacts for the service/core, click here or email Sue Ellen Martin, MD, PhD, director; sue.martin@med.usc.edu

2. USC Clinical Laboratories
The clinical laboratory supports research endeavors by providing information and services to approved protocols. It encompasses Keck Hospital, Norris Hospital, USC Clinical Laboratories Clinical Sciences Center, USC Westside Norris Lab, USC Clinical Lab in Pasadena, KH Newport Beach, the Newport Beach Clinic, and the Huntington Beach Lab.  An approved lab agreement must be on file, and a laboratory agreement and utilization worksheet need to be completed, signed by the PI, and submitted for review and approval to the Pathology Department (addressed to Susan McCarthy). Research protocols require copies of clinical laboratory licensure and accreditation be provided to them. Some research protocols request that testing be performed in the clinician’s office or other area (Point of Care testing), outside the knowledge of the USC Clinical Laboratory. Notify the laboratory if you are performing any testing (including dipstick, urine pregnancy, glucose, hemoglobin, INR or other tests) within your area that is a part of the research protocol. 

USC Clinical Laboratories: Initiate Lab Agreement: Susan McCarthy, Chief Administrative Officer at susanmcc@med.usc.edu

Regulatory Information: Marianne Silva; Manager of Quality, Regulatory Compliance at USC Clinical Laboratories; 323-442-8583 Marianne.Silva@med.usc.edu

3. Other Core Laboratories & Facilities
Other labs and facilities within USC, Keck, Norris, and CHLA can assist with processing specimens and cells (in areas such as genomics, flow cytometry, stem cells, molecular and cell biology, etc). For a complete list, click here.

Other Laboratories and Facilities: If you are having trouble identifying a laboratory or facility to assist with processing, please contact SC CTSI Clinical Research Support at crs@sc-ctsi.org


Section V. IRB Approvals Process

A protocol is a document that describes the background, rationale, objectives, design, methodology, statistical tests, and logistics of a research study. For an investigator-initiated trial, the PI is responsible for developing the protocol and associated documents such as the Case Report Form (CRF) and ICF. For a sponsored trial, the sponsor develops the protocol and associated documents. If the study involves multiple sites, all sites need to adhere to the protocol and the same processes so that the data collected as part of the study is valid and uniform across sites. In addition, all research staff must strictly adhere to the protocol when carrying out the study.

A protocol template for an investigator-initiated trial can be found here. For investigator-initiated non-cancer studies, the SC CTSI Biostatistics, Epidemiology and Research Design (BERD) group can provide assistance in protocol development. For cancer studies, Norris Cancer Center’s Clinical Investigations Support Office (CISO) can assist with protocol development. For more information about both of these resources, see Section IV, B. Study Design and Biostatistics Resources.

The IRB Submission Tracking and Review System, called iStar, is the online IRB application system used at USC. All IRB-related correspondence and documentation must be submitted through iStar. An iStar training site, FAQs, how to create an iStar account and other information may be found here.

iStar is used to complete the following functions, among others:

  • Create and edit an electronic application for submission to the IRB
  • Identify study staff and training
  • Attach study documents
  • Track the progress of an application as it is automatically routed for review and signoff to the appropriate organizations (i.e., division and department reviewers) before being received by the IRB
  • For communications between IRB and study staff
  • For receipt and download of the study approval letter and all approved study documents

The CRC is often responsible for the iStar submission. The PI, however, must always review and approve the application before it is submitted for IRB review. The PI must personally answer questions pertaining to any conflicts of interest, though the CRC may verify that this is completed. Changes to the IRB submission required by the sponsor as well as other sponsor interactions are the responsibility of either the CRC or PI. 

The University has also agreed to adhere to the statements of ethical principles as described in The Nuremberg Code, The Belmont Report: Ethical Principles and Guidelines for the Human Subjects of Research, and the Report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. This fundamental commitment to the protection of human participants applies to all USC research involving human participants regardless of whether the research is funded through the university, the federal government, a non-profit or industry sponsor and regardless of the location of the research. Read more about Human Subjects Policies and Procedures here.

Overall, the PI is responsible for the entire study and the research coordinator is responsible for implementing the study and supporting the ethical, regulatory, and sponsor requirements. 

iStar Technical Support: 323-276-2238; istar@usc.edu

CRCs may be responsible for writing and/or administering informed consent to participants, and therefore need to be knowledgeable about both the study content as well as the informed consent process. Informed consent is about protection and respect for research subjects. The requirement and content of consent varies according to the level of review and the nature of the research.

The Informed Consent Form (ICF) must contain: the purpose and procedures involved in the research; alternatives to participation; all foreseeable risks and discomforts to the subject (e.g. physical injury, psychological, social, or economic damage); the benefits of the research to subject and/or society; person to contact for answers to questions or in the event of a research-related injury or emergency. For IITs, the PI and study team are responsible for writing the ICF. For industry-sponsored studies, the ICF is provided and the IRB accepts these forms with minimal change to formatting. The IRB will require the study team to add USC specific requirements, like local contact information, cost and injury payment language, and removal of HIPAA. For a template ICF that can be modified for your study purposes, click here.

In the state of California, clinical trial participants must be presented with a copy of the Experimental Subject’s Bill of Rights only if the trial is considered a medical experiment. If your research is a “medical experiment,” participants must sign the Experimental Subjects Bill of Rights. Section 24174 of the California Health and Safety Codes defines a “medical experiment” as:

(a)        The severance or penetration or damaging of tissues of a human subject or the use of a drug or device, as defined in Section 109920 or 109925, electromagnetic radiation, heat or cold, or a biological substance or organism, in or upon a human subject in the practice of research of medicine in a manner not reasonably related to maintaining or improving the health of the subject or otherwise directly benefiting the subject;

(b)        The investigational use of a drug or device as provided in Sections 111590 and 111595;

(c)        Withholding medical treatment from a human subject for any purpose other than maintenance or improvement of the health of the subject.

Waiving one or more of the elements of informed consent may be permitted by the IRB for some research activities when justified. Informed consent elements that do not apply to a specific study need not be provided in the consent.

In all cases, the informed consent must:

  • Be presented in a language understandable to the participant
  • Minimize the possibility of coercion or undue influence
  • Allow participants sufficient time to consider participation
  • Allow participants to refuse or discontinue participation at any time
  • Distinguish between research and routine medical care
  • Be appropriately presented for the participant’s physical, emotional and psychological capacity, and vulnerable status
  • Assure that the participant understands what participation entails

Other types of informed consent include: parental permission, assent, verbal consent, short form, and information/fact sheet. The study protocol and study population will dictate which of these are required.  For further information on each, see the OPRS website.

If a participant is unable to provide consent, consent can be obtained by a Legally Authorized Representative (LAR). The HHS defines an LAR as “any individual person, judicial body or other body of individuals who are legally authorized under state and federal law to consent to research participation on behalf of a designated person.” This person can be appointed when an adult is unable to make or communicate an informed decision due to mental or physical impairment. For more information on LARs, click here.

1. When to Use a “Short Form” for Consent

For research participants who don’t speak and/or understand English, a “short form” is used, depending on the situation. If the participant understands the language being used to consent, he or she (or their LAR) can sign the consent form, as well as the person obtaining consent. The participant then receives a signed copy of the consent form. If the consent form includes the California Subject Bill of Rights, the participant must sign the first page (Bill of Rights) and last page (consent).

If the participant does not understand the language being used to consent, the person obtaining consent use the short form and California Subject Bill of Rights in the language spoken/understood by the participant. The person obtaining consent signs the consent form, and the witness signs the short form and the consent form. The participant (or LAR) receives a signed copy of the short form, Bill of Rights, and the consent form.

Finally, if the participant is capable of providing consent but has a condition that impairs consent documentation, such as illiteracy or blindness, the participant (or LAR) signs the consent form by making a mark, the person obtaining the consent signs the consent form, the witness signs the consent form, and the participant receives a signed copy of the consent form. If the consent form includes the California Subject Bill of Rights, the participant must sign the first page (Bill of Rights) and last page (consent).

For a complete guide to consent and short forms including copies of the California Bill of Rights in various languages, click here.

1. Departmental Review

At USC, all research conducted on the Health Sciences Campus must have departmental approval before the IRB will conduct its review. The department chair must attest to the scientific merit and feasibility of the application, the availability of needed resources, and departmental acceptance of the study. This process also serves to alert department chairs of all research under their purview, as well as provide an opportunity to note potential conflicts of interest which they may be aware of due to their role of reviewing all outside consulting under the Relationships with Industry policy.

All investigator-initiated non-cancer clinical trials that have not undergone prior scientific review by a qualified scientific body are automatically routed to the SC CTSI Clinical Research Support Scientific Protocol Review Committee to undergo scientific and feasibility review as a part of the IRB review process. CRS review aims to improve scientific rigor, methodological and statistical validity, and operational feasibility by providing useful feedback to investigators and study teams prior to IRB submission. The standing committee of reviewers includes a scientific review chair, statistical and methodological experts, disease-area experts, feasibility reviewers, and administrators.

After reviewers have completed their reviews, feedback will become available in iStar. The PI or study team should respond to each contingency in a point-by-point manner within 10 business days. At this time, PIs whose studies are not automatically routed to undergo scientific review by CRS cannot request this service on an ad-hoc basis. 

SPRC: CRS Research Liaison Brittany Gibbons, Brittany.Gibbons@med.usc.edu, 323-442-CTSA.

Depending on the nature of the study, approval from certain ancillary committees may be required before the IRB will issue final approval. These ancillary committees meet monthly.

At USC, authorizations or approvals for research may be required from:

The IRB will provide guidance to study staff questions regarding what ancillary approvals must be obtained based on materials, methods, or protocol. Obtaining these approvals will occur in parallel. The CIC reviews all cancer studies before submission to the IRB.

Amendments are changes to an IRB-approved research protocol. Amendments must be submitted in iStar and approved by the IRB before being implemented. Examples include revisions to consent documents, changes in PI, and inclusion of additional risks. Amendments involving more than minor changes or changes that pose more than minimal risk will be subject to Full Board Review.

Some changes may require changes in the budget or contract agreements with the funding entity, so the CTO or DCG must be notified (CTO for sponsored projects; DCG for federally-funded projects). More information about amendments can be found here.


Section VI. Study Conduct

1. Developing SOPs

The creation and implementation of Standard Operating Procedures (SOPs) is a crucial aspect of preparing for the study conduct phase. SOPs should be written by the primary study coordinator with input from other research personnel including the PI and project manager, if applicable. Within the SOPs, study teams should include very detailed information about routine procedures and processes associated with the study. Ideally, SOPs should be written in such a level of detail that a coordinator that is covering for the primary CRC would know how to carry out the tasks. A template example of an SOP can be found here. SOPs should be customized to the study and updated regularly, as processes and information change.

2. Participant Recruitment

Setting and meeting accrual goals are crucial aspects of ensuring a study’s success. Two centralized resources exist to provide strategies and tailored recruitment support:

  • SC CTSI can provide resources, tools and strategies for recruitment that are tailored to a study’s accrual goals, timeline, and budget. Three core groups at CTSI can assist with recruitment: Clinical Research Support, Community Engagement, and Digital Innovation and Communications.

Clinical Research Support (CRS) provides tailored recruitment plans, digital and traditional recruitment strategies, health communication best practices for engaging and retaining participants, creation and design of flyers, postcards, business cards and brochures (in both English and Spanish), and hands-on social media recruitment training for study staff.

CRS at SC CTSI: Contact CRS Program Manager Nicki Karimipour at Nicki.Karimipour@med.usc.edu or 323-442-1280

Community Engagement (CE) engages a broad spectrum of communities across the continuum of clinical and translational research, with particular emphasis on diverse and underserved communities, including pediatrics. The group helps researchers understand the health needs and research barriers of special populations and then facilitates academic-community partnerships to ensure patient/community engagement in all stages of clinical and translational research. CE also evaluates and disseminates novel approaches for engaging diverse populations in clinical and translational research and eliminating barriers to research participation.

CE at SC CTSI: Contact CE Program Specialist Mayra Rubio-Diaz at mayrarub@med.usc.edu or 323-442-1157

Digital Innovation and Communication (DI) leverages unique strengths of USC and private sector innovators to develop, demonstrate and disseminate digital solutions for challenges in clinical and translational research and education. Some examples include digital tools to engage diverse communities in clinical research, to increase public awareness and understanding of clinical research, to enhance recruitment of participants into clinical studies, to help researchers find collaborators and resources, and to enhance the digital capabilities of clinical researchers. SC CTSI’s Digital Innovation core also provides assistance with digital and social media recruitment through the use of an automated system developed by CTSI called Trial Promoter, which allows the automation of recruitment through social media platforms like Facebook and Twitter.

DI at SC CTSI: Contact DI Director Katja Reuter at Katja.Reuter@med.usc.edu or 323-442-2046

SC CTSI has also produced various guides and toolkits outlining best practices in community engaged recruitment, traditional and digital recruitment:

The Clinical Studies Directory of USC contains study landing pages that automatically pull study-related information from ClinicalTrials.gov. However, study teams at USC have the option to personalize their own free landing page in order to make it as patient-friendly as possible. As such, study teams can create and self-edit their own pages. Study teams must get the page IRB approved before it can be made publicly available. Directions and more information for how to create your own landing page are included in the link above.

CISO provides recruitment support for studies taking place at USC Norris Comprehensive Cancer Center. Strategies may include physician referrals, cohort identification, and communication strategies to engage patients with cancer diagnoses.

CISO: To obtain recruitment assistance, contact Zeno Ashai at 323-865-0463 or Zeno.Ashai@med.usc.edu

Finally, for prospective participants who are interested in learning more about the ongoing research taking place at USC, please refer them to the Office of Research “For Patients” website.

2. Parking Permits

Transportation and parking can often be a barrier to participant recruitment, so study teams should consider reimbursing for or providing validated parking passes for participants. USC Transportation Services offers daily parking passes for its various on-campus parking lots, as well as a longer-term pass that can be purchased for a few months (or for the study duration). A daily pass costs $12/day and a longer-term pass costs $111/month. To learn more about various options and to purchase a pass, click here.

If parking permits are being purchased through a department, an internal requisition form will need to be completed. Once completed and approved by the department’s financial contact, a copy of the signed requisition with the account number should be taken to the parking office located on the first floor of the Keith Administration Building (KAM) in exchange for the parking passes. Passes should be stamped with the date of the visit and participants should display their pass in their vehicle dashboard while parking in a USC lot. To inquire about obtaining parking validation for the hospital parking lots or various lots/structures on HSC campus, contact the HSC Office of USC Transportation. 

USC Transportation: UPC offices 213-740-3575. HSC offices 323-442-1201.

3. ClinCards and Planning for Participation Compensation

During this phase, study teams should be thinking about how they plan to compensate participants. At USC, ClinCards are reloadable debit cards that can be used to compensate participants in industry and non-industry human studies. These debit cards can be used for point of sale purchases with merchants that accept MasterCard, for bank teller withdrawals, and for ATM transactions. CRCs should budget up to 2 weeks from time the order is placed until the ClinCards are received. Click here for more information on the process, under “Prepaid Recurring ClinCards” (it will require you to log in using USC credentials). Purchase of ClinCards must be done through USC eMarket.

ClinCards: 213-740-6015; prepaidcard@usc.edu

1. Research Order Forms

Before scheduling any study-related ancillary service such as a study-related test and/or procedure, a Research Order Form (ROF) must be established for the study. The ROF serves as a clinical order for the various tests and procedures, and outlines which services are billable and payable as part of the study. CTO creates the ROF following review and budget/contract negotiation, and the ROF can be found in OnCore. Billing Auditors will use the completed and signed ROF to bill charges to the appropriate payer based upon the coverage analysis.

GE Centricity Business Billing System
CTO will register participants study information and financial class in GECB Billing System within 24 hours of notification of enrollment from study team. This will activate the Clinical Trials Patient Alert (flag) to Keck, Norris and USC Care providers.

OnCore
OnCore is managed by CTO and contains study participant information, study calendars, research order forms and coverage analysis for clinical trials. It is also used to develop internal budgets and track pre-award activity and post-award patient visit tracking and billing. For industry-sponsored studies, forms should be uploaded to OnCore within 24 of consenting a participant to a study.

For studies that are ongoing and actively enrolling participants
The study coordinator or research staff member is responsible for uploading signed ICF and HIPAA forms to OnCore within 24 hours of consenting a participant. They are also responsible for entering the participant’s information and details about their visit in OnCore

1. Health Insurance Portability and Accountability Act

The Health Insurance Portability and Accountability Act (HIPAA), also known as the “Privacy Rule,” establishes minimum Federal standards for safeguarding the privacy of individual’s identifiable health information. The law, overseen by the Office of Civil Rights within HHS, generally prohibits health care providers such as health care practitioners, hospitals, nursing facilities and clinics from using or disclosing protected health information (“PHI”) without written authorization from the individual.

USC requires all faculty, staff and other USC employees, as well as students, volunteers, agents and certain other individuals who have access to patient health information through USC providers, to complete an online course on the HIPAA Privacy Rule. The course may be accessed on the Office of Compliance website. In order to obtain access to OnCore, research staff must also complete the HIPAA training via the USC HealthStream website.

The Privacy Rule provides several methods by which a human subject’s health information may be obtained in connection with a research study:

Generally, researchers must obtain a written HIPAA Authorization from human participants (in addition to informed consent) when conducting a research study using PHI. The HIPAA authorization allows a researcher to use PHI for specified research purposes (not including treatment, payment, or health care operations), or to disclose PHI to a third party specified by the individual. A copy of USC’s HIPAA Research Authorization template can be found here.

A HIPAA Waiver or Alteration of the authorization requirement allows researchers to use or disclose PHI without obtaining authorization from participants as long as certain criteria are met:

  • The PHI will be protected from improper use and disclosure;
  • Identifiers will be destroyed at the earliest opportunity consistent with the conduct of research;
  • PHI will not be reused or disclosed to any other person or entity (except as required by law, for authorized oversight of the research study or for other research for which the use or disclosure of PHI is permitted by the Privacy Rule);
  • The research could not practicably be conducted without the waiver or alteration;
  • The research could not practicably be conducted without access to and use of the PHI.

The university’s IRB may approve a waiver or an alteration of the authorization requirement in whole or in part.

The IRB is charged with ensuring that all researchers and their staff who need to access PHI are HIPAA compliant. In this capacity, the IRB will determine whether the research participant must sign a USC HIPAA Authorization (in addition to the informed consent form for the study), whether the authorization requirement can be waived, or whether authorization is not required. iStar provides additional information about the circumstances when a waiver of HIPAA authorization may be appropriate.

Typically, at the time of enrollment, the participant signs the HIPAA research authorization and his or her informed consent. This enables the research team to obtain the health records that are covered by the authorization from the participant’s healthcare provider. It is critical for CRCs to obtain a signed copy of the current, IRB-approved HIPAA authorization and maintain the authorization in a clinical trial/research binder so that it is available for inspection and audit. 

USC’s HIPAA Privacy and Security policies and procedures are available on the USC policies website, or the USC Office of Compliance website.

Federally funded and/or FDA-regulated research must disclose the following to the sponsor, IRB, and FDA or OHRP as required:

  • Adverse Events
  • Unanticipated problems involving risks to participants or others
  • Protocol violations
  • Serious or continuing noncompliance with federal regulations
  • Serious or continuing noncompliance with requirements of the IRB
  • Suspensions or terminations of IRB approval

Reportable events must be disclosed to the IRB through the Reportable Events Application in iStar. Report contents must include the IRB study number; a detailed description of the event, incident, experience, and or outcome; and a description of corrective actions that have been taken or are proposed. The IRB determines when these events must be reported to federal agencies.

The different terms used by OHRP (Unanticipated Problems involving risks to participants or others) and FDA (Adverse Events) are among the most common reportable events and easily confused. The table below distinguishes the two.

Regulatory Terminology for Unanticipated Problems vs. Adverse Events

 

OHRP

Protection of Human

Subjects (45 CFR 46)

FDA

Investigational New Drug Applications (21 CFR 312.32) Investigational New Device

Exemptions (21 CFR 812.150)

Event Type

Unanticipated

Problems Involving Risks to Subjects or Others

Adverse Events

(Internal/External)

Context

Occurs in clinical or non-clinical research

Occurs in clinical research only

Scope

Untoward event in ANY aspect of a research study

Untoward response to a test article (e.g. drug, device, biologic)

Involve

Could be subject, study staff or others

Subjects only

Expectation

Unanticipated

  • Anticipated (an increase in frequency, duration or intensity beyond expectations)
  • Unanticipated

 

Reporting

Prompt reporting to IRB

required (not to exceed 10 working days)

Prompt reporting to IRB required (not to exceed 10 working days)

How to Report

iStar reportable event application

iStar reportable event application

1. Adverse Events, Serious Adverse Events, Protocol Deviations, and How to Report Them

PIs and research staff must follow institutional policies for documenting and reporting adverse events, serious adverse events, and protocol deviations that may occur during study conduct.

Adverse events (AEs) are defined as “any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research.” Information regarding the submission of Adverse Events to the IRB can be found here. This link also provides information about how to determine what type of adverse event has occurred.

Serious adverse events (SAEs) are defined as events that are life-threatening, such as death, birth defect, hospitalization or prolonging of existing hospitalization, “persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions,” according to the UCSF CTSI guidelines on AEs and SAEs.

Reporting an AE or SAE at USC involves filing a report with the IRB, including the necessary documentation that shows the event was reported with the study sponsor and FDA if needed. Section 2 of this website provides more guidance on reporting various events in iStar. More information from the OPRS website about AE & SAE reporting can be found here.

Protocol deviations are defined as any accidental or unintentional change to or noncompliance with the IRB approval protocol without prior approval. Violations can be minor or major, and major deviations may increase risk or otherwise compromise a participant’s rights, safety, welfare, or influence data integrity, and must be reported. The IRB of record must be notified of deviations in writing including details such as the date of the deviation, description of the situation, what steps were taken to address the issue with the participant, how the study team plans to reduce likelihood of a repeated incident, etc. Section 15 of this website provides more guidance on reporting protocol deviations. 



After IRB approval, the research staff will have to prepare for routine sponsor monitoring/auditing visits. Sponsors will send a monitor to look into how the site is adhering to the protocol, keeping data and study-related records, and more. Common reasons for problems associated with monitoring visits include failure to comply with the protocol/protocol deviations, failure to keep accurate records, problems with informed consent, not reporting adverse events in a timely fashion, and problems with keeping the study drug inventory.

The RKS group at the SC CTSI also provides routine monitoring and auditing performed by research-trained personnel who are independent of the study.

For research groups at USC who want to train their own monitors, access the free training modules created by RKS here.

RKS: Amelia Spinrad; Spinrad@med.usc.edu; 323-442-1598


Section VII. Data Collection and Analysis

During the data collection phase, CRCs will obtain data during or after the participant’s study visits. He/she will enter this data into a paper or electronic CRF. HIPAA compliant case report forms can be created and hosted through various platforms such as REDCap for investigator-initiated studies. For industry-funded studies, the sponsor typically hosts their own electronic data capture platform, and provides specific training for how to use the platform.

In order to keep up with participant data, it is best practice for the CRC to transcribe data into the paper or eCRF promptly after the study visit to decrease possibility of error or omission. Furthermore, sponsor payment to the site often depends on receipt of complete CRFs.

Source documentation is used to provide justification or proof for data collected as part of a research study. Examples of source documentation include hospital records, medical charts, lab values, subject diaries, pharmacy dispensing records, x-rays, and more. The sponsor or CRO sends Clinical Research Associates (CRAs) to do the source document verification, which involves comparing the source documents with what is recorded in the CRF to ensure it complies with the protocol, GCP and that entries are accurate and complete. 

Per ACRP, best practices for completing source documentation can be summed up by the following acronym, ALCOAC:

  • Signing and dating of tasks: Attributable
  • Readable documentation: Legible
  • Documenting at time of patient visit: Contemporaneous
  • Derived from source documentation: Original
  • Documenting all facts: Accurate
  • Documenting all information: Complete

1. SC CTSI Biostatistics, Epidemiology & Research Design 

SC CTSI BERD can assist with data management plans during the initial consultation phase. For IITs, common aspects to consider that also have regulatory implications include how data will be stored (physically & digitally); how data will be analyzed; what statistical tests will be used; etc. For more information about BERD recharge rates, click here. The consultation is free, up to one hour. 

BERD: To request a consultation, click here.

2. Norris CISO Biostatistics Core

The Biostatistics Core at CISO can assist PIs working on clinical, basic science, and cancer cause and prevention studies. According to their website, the Biostatics Core statisticians work with CISO by participating in the planning, monitoring, and analysis of in-house clinical trials approved by the Clinical Investigations Committee (CIC). These biostatisticians can help with participating in research design, assisting with data management, and statistical analysis. 

Norris Biostatistics: For contact information, click here.

3. REDCap 

REDCap is a secure web tool used for building and managing online surveys and databases for research studies. It is designed to comply with HIPAA regulations, is commonly used as an eCRF as it allows for real-time data entry validation, audit trails, ability to set up a calendar to schedule/track critical study events like blood draws and visits. Data from REDCap can be exported for analysis into Excel, SAS, SPSS, STATA, and R. It can be used across multiple sites and is free for USC faculty, students, and staff. To get started, click here.

REDCap training is held every semester, and attendees are encouraged to bring a project with them to work on during the training. Research staff is encouraged to sign up for the SC CTSI listserv to be notified via email about upcoming REDCap training opportunities. Typically, a training session is held each semester – and “lunch and learn” events geared toward PIs are held multiple times throughout the year.

The aforementioned biostatistics resources can also assist with helping study teams develop a data management plan to outline and address issues such as data storage, data collection; access, sharing, and data preservation, during the data collection phase and after the project is completed.

Clinical Research Informatics: cri@sc-ctsi.org; 323-442-0217

During the data analysis phase, the study team will work on cleanup of the data, finalizing entries in CRFs, and later, respond to queries from the statistical team or sponsor. Queries are defined as data inquiries generated by the sponsor or biostatistician. Queries are generated from missing information, illegible responses, incorrect format of information, inconsistent responses, and more. An example of data that could lead to a query is mistakenly indicating “yes” for pregnancy for a male participant. The research site is responsible for resolving these queries by rechecking data or source documentation. 


Section VIII. Study Closeout

A research project must be closed when subject accrual, subject follow-up and data analysis are completed. Upon study completion, the PI or other study personnel must submit a Close Study application to the IRB through iStar indicating the study status as “closed.” Doing so confirms the study is finished and that no further interactions with subjects or their data will take place. Additionally, no further research activity, including data analysis, may occur once a study is closed.

The IRB, in consultation with the CRC or PI, may also close a study when active data analysis and publication have ceased, even if the researcher retains records that may identify individual subjects. Once the study is closed in iStar, yearly continuing review applications are no longer required. Additional research activities using data collected in an approved study may constitute new human subjects research studies subject to separate IRB review.

If a PI wishes to enroll new subjects to a closed study, a request can be made in iStar to reactivate the study. Once the study has been reactivated, a continuing review application must be approved by the IRB before study activities can resume.

It is permissible for a study to be closed at USC, and still be open to accrual at other sites. In the event that a serious adverse event or an unanticipated problem occurs at a non-USC site after closure of the study at USC that may affect the study subjects, the USC CRC is required to submit a report to the IRB via iStar.

Much like SIVs that take place at the initiation of a study, Closeout Visits (COVs) occur as part of the closeout process. The purpose of the COV is to ensure the site has met its obligations to the sponsor and any post-study items have been completed. The sponsor staff will ensure that study procedures, regulatory documents, CRFs and data are completed, and any investigational product or supplies have been returned to the sponsor or destroyed with proper documentation explaining the destruction. Queries have been addressed, protocol deviations, adverse and serious adverse events have been reported. The PI will need to be available to sign off on any documents required for the closeout. Closeouts can occur when the study has met the sponsor’s enrollment goal, but can also occur when the site is not accruing participants and the sponsor chooses to terminate the study. A final report will be prepared for the IRB and includes information such as study conduct and outcome, safety and efficacy observations, disclosing SAEs during the trial, and study closeout date. The PI will receive a CD or flash drive containing the electronic data in case of future audit. Study documents should be retained for a minimum of two years or more, depending on what is written in the protocol. The documents can be retained on or offsite depending on the sponsor’s requirements. When in doubt, clarify with the sponsor. 

Prior to close-out, the study team must budget for archiving and long-term storage of study-related documents, which includes physical and digital records. This process becomes even more critical during close-out. First, you must determine which regulation applies to your research, as there are differing timelines based on the type of regulation. For example, regulatory bodies such as the Office for Human Research Protections, HIPAA, Department of Veterans Affairs, and FDA all have varying timelines for keeping records. Additionally, if your study is under a grant or industry contract, you must comply with any terms for record retention outlined in the sponsor award.

If multiple regulations apply, the PI should keep the data for the longest required amount of time.

According to the Office for Human Research Protections, research records must be retained for at least three years after the research concludes. According to HIPAA, records must be retained for at least six years after the PHI was disclosed. VA research records must be retained indefinitely. Finally, per the FDA, study documents need to be retained for at least two years after an intervention has been approved for the indication for which it is being studied, or after the investigation has been discontinued. If the study is not part of a marketing application, the investigator needs to retain records for at least two years after the study is completed. The retention period may be longer for studies that are part of a multinational program.

For industry trials, the sponsor or CRO will typically provide guidelines for how to dispose of and store essential documents in a compliant manner. The monitor should check with the sponsor regarding document retention requirements before the visit in order to work with the site to ensure compliance. The sponsor should also send a letter to the site outlining the document retention requirements for the study. For investigator-initiated trials where the investigator is the sponsor, this sponsor-investigator needs to follow applicable regulatory requirements, site procedures, and grant stipulations, and any other policies applicable to the trial regarding document retention and storage. For IITs, documents should also be stored and archived based on the protocol or data and safety monitoring document.

When destroying paper records, they should be securely shredded. Local secure shredding companies provide such services at varying price points. For long-term storage solutions, companies such as Iron Mountain provide solutions for record management, data backup and recovery, document management, secure shredding, and more. For digital records, they should be password protected and encrypted. Computer records should be erased using commercial software applications designed to remove all data from the device. 

For assistance with this at Keck, contact the IT Helpdesk at 324-442-4444 or helpdesk@med.usc.edu. For assistance with this at LAC+USC, contact the Enterprise Help Desk at 323-409-8000.


Section IX. Dissemination

Preparing for dissemination of research findings involves formulating a strategy for dissemination. The first priority of such a plan (and per NIH policies) involves returning results to study participants in a timely manner, through open communication and updating ClinicalTrials.gov to ensure public-facing update of research findings.

Other strategies for developing a dissemination plan include identifying the goal, target audience, and appropriate medium for releasing study results and findings. Writing up a simplified outline of relevant and impactful findings will make it easier for stakeholders and media outlets to cover the research. 

A KSOM-specific document for how and why to promote research, including relevant contact info for the KSOM media relations team, can be found here.

Spreading the word about research findings within the Keck community and to the larger medical community involves liaising with communications experts and engaging in some promotional efforts. Keck Medicine of USC Marketing and Communications can assist with disseminating information in the form of press releases, articles and stories for audiences within and outside of our institution. 

Keck Marketing: prmarketing@med.usc.edu

Questions? Suggested updates to this document?

Please email CRS at SC CTSI: crs@sc-ctsi.org


Section X. Appendix

Investigator, or PI) working at an academic medical institution. A sizable portion of the PIs at USC have industry partners that fund the work. However, for IITs, the sponsor is the PI. As such, the PI formulates the idea for the study, the design, data plan, collection, analysis, and interpretation. The PI and study team are also responsible for obtaining approvals from various USC entities at varying stages in the process, including IRB, CTO or DCG, and coordinating ancillary services before carrying out the study, as well as for regulatory compliance with ClinicalTrials.gov.

In terms of funding sources, a federally funded study receives funding from federal agencies such as the NIH, HHS, DOD, or any associated institute or center. Industry-sponsored studies are funded by pharma or other for-profit entities and USC receives a protocol to carry out, which was written by the for-profit entity. Contract terms, budgeting, data collection, intellectual property and publication rights under an NIH study and industry study vary drastically. It is important to understand your obligations, as they often remain in place throughout the study and for years after its conclusion.

1. What is Human Subject Research?

At USC, human subject research involves studies that use human participants to evaluate or understand drugs, devices, and biologics. Research involving human participants can also be observational in nature, and involve the assessment of therapies or treatments relating to psychiatry, nutrition, and exercise, to name a few examples. These studies seek to answer questions of a biomedical or social-behavioral nature, and are subject to institutional policies and federal, state, and local laws.

Biospecimens stored in biorepositories (also called biobanks, registries, etc) are also considered a form of human subject research. Biorepositories collect and house biospecimens like urine, blood, tissue, cells, DNA, RNA, and proteins for laboratory research. For human biospecimens, medical information may also be stored along with written consent to use samples in future studies.  

USC’s policy on biorepositories is that the samples to be used for research are obtained, stored, distributed and used in a way that is compliant with all regulations and policies, and in a way that protects the rights and information of individuals who donated the samples. Submittal agreements must be used in order to ensure that the biospecimens were obtained with written informed consent from the donor using a consent form approved by the local IRB or pursuant to an IRB-approved waiver of informed consent. To read more about USC-specific policies on biorepositories, click here.

A clinical trial involves research with humans that involves an unapproved, FDA-regulated test article and one or more human participants. If the PI or study team intends to submit the results later to the FDA as part of an application for a research or marketing permit, it is considered a clinical trial. This process is described in more detail in the “Investigational Drugs & Device Applications” section.

2. What is the NIH Definition of a Clinical Trial?

According to the NIH, a clinical trial is defined as “a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes” (NIH.gov; emphasis added). The NIH issued this definition in 2014 and revised it in June 2017. An intervention is a manipulation of the subject or the subject’s environment to modify a health-related biomedical/behavioral outcome. For example, this can include biologics, drugs, devices, and procedures – but the delivery system can also be an intervention, like telehealth or interviews. Finally, certain strategies meant to modify a behavioral outcome, such as nutrition counseling or cognitive therapy, can also qualify as an intervention per the NIH definition. For case study examples from the NIH, click here.

  • USC Institutional Review Board

Institutional Review Boards (IRBs) are committees charged with reviewing research activities involving human subjects that are conducted at an institution or by an institution's faculty and students. The federal government and many organizations that fund research require IRB review of the research they fund. Unfunded or investigator-initiated research also requires IRB review.

USC IRBs are charged with assuring that the rights, safety, and well-being of human subject participants is maintained and that research is conduct in a manner consistent with the approved protocol. The IRB reviews research protocols to ensure the activity complies with University policies as well as federal, state, and local laws. The IRB has the authority to approve, require changes to the study procedures, or disapprove proposed research projects. 

PIs may be required to get approval from additional bodies before the IRB will conduct a review. These are called ancillary committees. Examples include institutional biosafety and radiation safety, and this is covered in detail under the Ancillary Committees section.

Federal regulations require that the IRB have at least five members. These members must include individuals from academic disciplines relevant to the research being reviewed and must include at least one non-affiliated member (at USC this person is referred to as a Community Member). The IRB should be diverse in terms of race, gender and cultural background. IRB members can be faculty, staff or students from the institution, as well as members of the local community. IRB members must have the necessary experience and expertise to competently evaluate the proposed research.

In the review process, the IRB may approve, defer, or approve with contingenciesContingencies are modifications required by the IRB.

The IRB reviews the following aspects of each study:

  • Description and research methodology*
  • Equitable selection of subjects*
  • Risks minimized*
  • Acceptable ratio of risks to benefits*
  • Vulnerable status of subjects*
  • Incentives for participation
  • Privacy and confidentiality*
  • Monitoring (frequency and mode)*
  • Informed consent content (required elements and types) and process*
  • Conflict of interest
  • Departmental resources/appropriate expertise of PI and study staff
  • Sponsor Requirements
  • Scientific values
  • HIPAA requirements
  • Full Board Review: Presents more than minimal risks to subjects and/or does not qualify for Expedited or Exempt Review
  • Expedited Review: Meets one of the 9 federally defined Expedited Review Categories (45 CFR 46.110); Reviewed by an IRB Chair/designee/staff; Not greater than minimal risk (including privacy risk)

* Approval criteria for IRB review of research

2. Levels of IRB Review

The population being studied and the level of risk associated with a research activity will influence the level of IRB review. There are three levels of review:

Examples of human subjects research activities reviewed by a Full Board convened IRB include novel investigations with experimental drugs or devices and documentation of illegal behaviors with links to subjects’ identifiable information.

Examples of expeditable research activities include collection of blood samples from healthy adults, and collection of biological specimens or data by noninvasive means (saliva, cheek swab, x-rays). 

  • Exempt Review: Must meet one of the 6 federally defined Exemption Categories (45 CFR 46.101); Must be reviewed by an IRB Chair/designee/staff; Must not present greater than minimal risk* (including privacy risk)

* Minimal risk means the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

Examples of Exempt research activities include measuring blood pressure and conducting anonymous educational tests.

3. Updates to the Common Rule

The “Common Rule” is a rule for the Protection for Human Subjects, published in the Federal Register as of January 2017. This revised rule, effective as of July 19, 2018, allows institutions reduce burden in three key areas for studies that are not FDA-regulated. As such, certain scholarly and government activities will no longer be considered research, IRB review won’t be needed for grant applications to the U.S. Department of Health and Human Services (HHS), and for most expedited studies, continuing review will not be needed anymore. Additional provisions include the requirement for consent forms to include an initial summary of “key information” about the study and to better provide an understanding of risks and benefits to participants can make an informed choice about participation. Multi-site studies funded by NIH requires the use of a single IRB (sIRB) as of January 25, 2018. Beginning January 2020, USC participation in any multi-site research must rely upon a single IRB (for research conducted in the U.S.). Researchers will not have to obtain consent for studies on non-identified stored data or biospecimens (this requirement remains the same as with the previous rule), and finally, the requirement that consent forms for certain federally-funded trials should be posted on a public website.

Under the revised Common Rule, continuing review isn’t needed for research eligible for expedited review, exempt research conditioned in limited IRB review, research that has completed all interventions and is only in the data analysis phase (even if information/biospecimens are identifiable), and research that has completed all interventions and is in the follow-up stage. For full information about all Common Rule changes, please visit the HHS website.

In terms of the roles and responsibilities of CRCs, they must be appropriately trained and credentialed. CRCs’ main tasks are to assist the PI in developing study-related documents as part of the initiation of a new clinical trial; upload a copy of the signed informed consent and HIPAA research authorization into OnCore, enter patient information and visit details; and use the Research Order Form from OnCore to schedule all services for each participant. They may also be asked to assist with developing a study budget, putting together and submitting regulatory materials including IRB applications, recruiting participants, scheduling participant visits and coordinating their ancillary appointments (i.e. for MRIs, scans, etc), entering and cleaning data, liaising with sponsors and other entities, and any other relevant study-related tasks as are relevant and within the scope of the study’s delegation of authority log. Above all, the coordinator must strictly adhere to the study protocol. A useful explanation of what a delegation of authority log is, as well as a suggested template, is provided here.

In addition to funding from federally funded agencies, there are some institution-specific funding sources that PIs can leverage:

  • The Dean’s Pilot Funding Program offers up to $37,500 for one year (2:1 ratio of funds provided from the Dean’s office and the PI’s home department or Institute). The letter of intent deadline is usually in mid-August. For more information including deadlines, eligibility and review criteria, access the RFA.
  • LAC/DHS Implementation Science Award offers one award up to $75,000. One award is given out at USC and UCLA per year. The purpose of the award is to support projects that support the design and small scale implementation of interventions within DHS that will achieve the goals of quality, efficiency and patient centered care. For more information including deadlines, eligibility and grant conditions, access the RFP.
  • The Ming Hsieh Institute for Research on Engineering-Medicine is focused on translational cancer research and is offering an award up to $140,000 to fund proposals that will initiate new Nano medicine multi-disciplinary projects that show exceptional promise for translation into human clinical trials for cancer treatment; or aim to develop new targeted immunotherapeutic approaches to cancer. The application deadline is usually in mid-January. For more information including deadlines, eligibility and grant conditions, access the RFP.

For a full list of funding opportunities maintained by the USC Office of Research, click here.

The SC CTSI hosts three main funding opportunities to support clinical and community research projects: 1) Pilot Awards, 2) Team-Building Awards, 3) Voucher Awards.

  • The annual Pilot Awards offer up to $40,000 each to fund individual PIs or small research teams in two areas: clinical and community research, or improving research methods and processes. Neither funding mechanism is intended to fund basic or preclinical research. These awards are intended to support preliminary research that will lead to larger extramurally funded human mechanistic studies, clinical trials, community trials, health outcomes research, or implementation research. For the research method/process improvement awards, they are intended to support the development and testing of new approaches and/or tools that increase the speed, efficiency, safety and/or quality of clinical, community, health outcomes and/or implementation research. Highest priority will be given to projects that demonstrate a clear path to sustaining extramural funding or to direct implementation of improvements in clinical and translational research processes. The PI’s commitment to a career in research will be considered a plus. Department or Institutional cost-share is required at a 4:1 ratio. Proposals will be evaluated using an NIH-style peer review process. Full-time faculty at USC and CHLA are eligible to apply. For more information, please click here or contact the SC CTSI Research Development team at rd@sc-ctsi.org.
  • SC CTSI also offers a team-building grant of up to $5,000 to support research team formation. It is intended to provide rapid funding for activities that promote the assembling of new multidisciplinary or transdisciplinary teams focused on clinical and community research that are grounded in the team science principles. Funds can be used for activities such as scheduling conferences, seminars and workshops; exploring virtual team platforms, and development of new interdisciplinary partnerships. Full-time USC or CHLA faculty are eligible to apply. Pre-submission consultation is required. For more information, please click here or contact SC CTSI Research Development team at rd@sc-ctsi.org.
  • Finally, SC CTSI CRS offers Voucher Awards up to $3,000 each to jumpstart clinical or community research that will generate key preliminary findings for more impactful funding at USC and CHLA. The funds can help add new data collection to an existing clinical or community research project that would otherwise lay outside the scope of the parent project; or they can enable de novo data collection outside the context of any existing project. This funding can be used to purchase core resources such as pathology, compensation for research participants, and more. Click here for or a full RFA. For any questions, email CRS Research Liaison Brittany Gibbons.

Finally, the Grant Forward database allows users to search for funding opportunities at the federal and state level, as well as for foundation funding and institution-sponsored funding. Grant Forward collects funding announcements from all fields, and access is free for all USC employees. 

The Norris Medical Library provides assistance with systematic literature reviews, bioinformatics services, and other resources to assist with the research preparation process. For a list of library liaisons to contact for more information, click here

The USC Office of Research’s Center for Excellence in Research (CER) offers multiple tools and guides to assist with proposal and grant writing, based on the specific federal agency. There are guides for proposal development, navigating the application process, and advice for tailoring submissions based on the agency. Proposal and grant writing guides based on the specific federal agency can be found here, in order to assist with proposal development, navigating the application process, and advice for tailoring submissions based on the funding agency.

The CER also offers a proposal review service through the Center for Excellence in Research. In order to take advantage of this service, PIs should notify Araceli Roach as soon as they identify the funding opportunity to which they intend to apply (or roughly four to five weeks in advance of the proposal due date), indicating the nature of the proposal and providing a link to the program announcement.

In addition, CER provides several trainings and resources for grant writing. Many of these trainings are in-person workshops and courses that take place at UPC and HSC. Some workshop offerings include courses on developing NIH grant applications, writing compelling NSF proposals, navigating the grant proposal landscape for junior faculty, and informational sessions about USC awards to fund research.

For a list of updated workshops and classes, click here. To register, CER asks that you RSVP one week prior to the class via email by indicating which sessions you will be attending. Email USCCER@usc.edu or call 213-740-6709.

Keck School of Medicine has a pre-grant review program that can help support new PIs applying for their first NIH R01, R21, K99/R00 or comparable federal research grant. Reviews will address general grantsmanship including effectiveness of presentation, flow and quality of supporting documentation, and scientific content. For questions, contact Sarah Hamm-Alvarez, PhD: shalvar@med.usc.edu.

Finally, USC currently does not currently offer a formalized service for grant writing assistance, but can recommend private companies. Please contact the SC CTSI Research Development core for more information at rd@sc-ctsi.org.

Dimensions is a database for identifying collaborators worldwide. This database contains a list of all funded research around the globe, including clinical trials, grants, publications, and patents. The search tool allows you to segment the search by researcher, funder, country, institution, publication year, research field, and more. Dimensions can be accessed through this link, and access is available to those who are on campus and using on-campus IP ranges – or through the VPN for those who are off-campus. A video explaining how to use the platform can be found here.

To identify local collaborators in a given research area, an online networking tool called USC Health Sciences Profiles lists USC faculty and staff based on name, research topic, school, department, and more. HSC Profiles contains data on more than 62,000 publications and 350 clinical trials.

SC CTSI’s Research Development core can also assist in facilitating interdisciplinary research collaboration through consultations, and through funding (Team Building grants, discussed on page 9).

Another important aspect of preparing to conduct research is negotiating authorship. Click here for guidance from the USC Office of Research on how to assign authorship in research studies and creative works.

1. Facilitating Multisite Research Collaboration

The NIH has implemented a new collaborative network called the Trial Innovation Network (TIN), charged with streamlining the conduct of multicenter studies through a central IRB, standard agreement, and site-specific participant recruitment strategies. Proposals are accepted on a rolling basis from a wide range of disciplines, and the Network prioritizes proposals with patient-oriented endpoints with potential for impact on clinical practice.

USC investigators can participate in TIN as a participating site or as the initiator of a multicenter study if they submit a proposal through TIN. The SC CTSI provides free resources for PIs planning and initiating a multicenter study through TIN. To be considered a multicenter study, there must be three or more study sites (affiliate sites such as CHLA and LAC+USC fall under the umbrella of USC and therefore are not considered a separate site). The free resources provided by the CTSI include additional biostatistics hours, budgeting assistance, submission of regulatory documents and a discounted rate on hiring a CRC through the SC CTSI CRS group. Funding sources for TIN include NIH Institutes and Centers such as the NHLBI and NIA, PCORI, foundations and other non-profit organizations, and existing cooperative disease research networks such as the ADCS, Alzheimer’s Disease Cooperative Study.

USC’s hub liaison team, pictured below, is comprised of individuals from various offices at USC including the CTO, DCG, IRB, OPRS, and CTSI, and is here to assist and provide information and resources to PIs and study teams. If you are interested in putting together a proposal for a multisite trial, or interested in collaborating with other institutions on multisite trials, contact Nicki Karimipour, USC TIN hub liaison administrator.

Research space at the Keck School is assigned to an investigator conducting research based on a couple of factors. The investigator must be a faculty member at the Keck School of Medicine with an active research program that is 1) bringing in extramural funding, and/or 2) is supported by start-up funds following a recent recruitment. For more guidelines regarding the space allocations, click here.

1. Protected Health Information: In certain situations, sponsors may wish to provide USC with identifiable health information (also known as Protected Health Information, or PHI) that is protected by state and/or federal privacy laws. In connection with doing so, they may require the university to agree to meet various data privacy and security requirements with regard to the receipt, maintenance and use of such data. In the event you become aware that a sponsor is requiring the university to agree to data privacy/security standards associated with the provision of identifiable health information, please contact the Office of Compliance for assistance.

2. Certificates of Confidentiality: Certificates of Confidentiality (CoCs) are documents issued by the National Institutes of Health to protect research participants’ identifiable research information from forced disclosure to anyone who is not connected to the research. This policy applies to research activities including biomedical, clinical, behavioral and other research involving human subjects, for which the study team is collecting/using biospecimens that are identifiable to a person who is part of the research (and/or if the research involves generation of individual level, human genomic data). 

CoCs allow the PI and others who have access to research records to refuse to disclose identifying information, document, or biospecimens associated with research participants in any civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or local level. CoCs may be granted for studies collecting information that, if disclosed, could have adverse consequences for subjects or damage their financial standing, employability, insurability, or reputation (i.e., sexual attitudes, preferences, or practices; information relating to the use of alcohol, drugs, or other addictive products; information pertaining to illegal conduct; information that, if released, might be damaging to an individual's financial standing, employability, or reputation within the community or might lead to social stigmatization or discrimination; information pertaining to an individual's psychological well-being or mental health; and genetic information or tissue samples).

NIH CoCs may also be authorized for studies not funded by NIH (i.e., NIH funding is not a condition for receiving a Certificate of Confidentiality). Click here for more information on CoCs, including how to apply for and obtain one.

3. MTAs, DUAs, Intellectual Property & Other Confidential Information

Material Transfer Agreements (MTAs) are contracts that allow investigators to share or receive tangible research material and software while protecting inventions and other types of intellectual property, limit liability, and provide proper crediting for the provider.

Data agreements (DUAs) (sometimes called Data Use Agreements, Data Access Agreement, Data Transfer Agreements, etc) are used in order to share various types of data between institutions or entities. In particular, DUAs covering patient-derived information can be used to allow institutions or entities to share data containing Protected Health Information (PHI) or de-identified patient information. As such, an agreement must be executed and on file in order to compliantly share this information. The agreement will outline permitted uses and disclosures of the data set, identify who may use or keep the information, outline how it will be shared, and more.

At USC, MTAs (both inbound and outbound), DUAs, and CDAs that protect intellectual property are handled by the USC Stevens Center for Innovation and must be signed by an authorized member of the Center. MTAs, DUAs and CDA requests can be submitted online using USC Net ID and password. To get started, click here.

Once an investigator submits an MTA, DUA, or CDA request form through the online portal, the request is reviewed initially by Sue Kim within 3 days. Depending on the details of the specific request, the Stevens Institute may have to confer with Compliance (patient identifiable information, audit language, export, etc.) or the General Counsel (liability language). For inbound transfers, the Stevens Center may also need to confer with the University from where the material or information is coming, which can cause delays. Depending on the complexity and details of the request, execution of the agreement can take anywhere from 2 days to 3 months. Investigators can check on the status of their request by using the online portal system.

  • USC Stevens Center for Innovation: For a full list of contacts based on department, click here.
  • For questions about MTAs, DUAs, or CDAs, contact Sue Kim, Senior MTA Administrator. suekkim@usc.edu; (213) 821-0939

Good Clinical Practice Guidance defines a clinical trial as any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product(s), and/or to identify any adverse reactions to an investigational product(s), and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the object of ascertaining its safety and/or efficacy. For clinical trials with drugs or biologics, the sponsor or sponsor-investigator must submit an IND application to the FDA. For clinical trials with devices, the sponsor or sponsor-investigator must submit an Investigational Device Exemption (IDE) application to the FDA. An investigation may begin 30 days after FDA receives an IND or IDE application unless FDA notifies the sponsor that the investigation may not begin. Additionally, IRB approval must be received before a site can begin screening and enrolling subjects.   

A sponsor-investigator is an individual who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. As the name suggests, a sponsor-investigator assumes the responsibilities of, and must comply with, FDA regulations applicable to both a sponsor and an investigator (New Drug Applications Prepared and Submitted by Sponsor-Investigators, FDA Guidance Document).

In some cases, approved drugs can be used for unapproved uses (this is also referred to as “off label” use). Using an approved drug in an “off label” manner can mean that a physician uses a drug to a disease or condition for which it is not approved to treat because the physician feels it will have therapeutic benefits. Or in another example, the drug can be administered a different way, such as when a drug is approved as a capsule but is administered in an oral solution. Finally, the dosing can also vary for approved drugs being used off label. If a physician decided to use an approved drug in an unapproved manner, the FDA has not determined that the drug is safe and effective in that unapproved use. For more information about off label uses, visit the FDA’s website.

Generally, FDA regulations require sponsors, including sponsor-investigators, who wish to evaluate a drug or biological product in humans to submit an IND to the FDA (21 CFR part 61 312).

A sponsor of a significant risk (SR) device study must submit a complete IDE application to FDA (IDE Application, FDA.gov). Under 21 CFR 812.3(m), a SR device means an investigational device that: • Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject; • Is purported or represented to be for use supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject; • Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or • Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject (Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors Significant Risk and Nonsignificant Risk Medical Device Studies, FDA Guidance Document).

Keck Medical Center of USC Research Board must approve any project involving a device. In many cases, a contract and a purchase order are required before study activation.

USC’s Regulatory Science consultants can assist with IND & IDE applications, marketing applications for drugs and devices, or answer any questions you might have.

Contact: Amelia Spinrad, Spinrad@usc.edu or 323-442-1598.

1. Approvals Process for Using Devices within Keck Hospital

If study proposes to use any equipment or devices (including implants or equipment of any kind), the Keck Medical Center Research Board notifies Keck Sourcing prior to completion of the CTO agreement. Keck Sourcing reviews study information and determines if device is a) standard of care or investigational, b) in-house or not in-house, and c) paid for by study or insurance. If device is standard of care, in-house, and paid for by insurance, study is approved. If device is standard of care, in-house, and paid for by study: Keck Sourcing negotiates and executes contract between medical center and vendor; Keck Sourcing creates a No Charge Purchase Order, and then the study is approved. If device is standard of care and not in-house or not paid for by study: Keck Sourcing sends request to the VAC, which meets monthly to review requests and determine outcomes. If not approved, Board notifies PI. If approved: Keck Sourcing negotiates and executes contract between medical center and vendor; Keck Sourcing creates a Purchase Order, and then the study is approved. If device is investigational, in-house, and paid for by study: Keck Sourcing negotiates and executes contract between the medical center and vendor; Keck Sourcing creates a No Charge Purchase Order, and then the study is approved. If device is investigational, not in-house and paid for by insurance: Keck Sourcing sends request to the VAC, which meets monthly to review requests and determine outcomes. If not approved, Board notifies PI. If approved: Keck Sourcing negotiates and executes contract between medical center and vendor; Keck Sourcing creates a Purchase Order, and then the study is approved. If device is investigational, not in-house or not paid for by study: Keck Sourcing sends request the VAC, which meets monthly to review requests and determine outcomes. If not approved, Board notifies PI. If approved: Keck Sourcing negotiates and executes contract between the medical center and vendor; Keck Sourcing works with the CTO office to evaluate funding of the device above and/or beyond insurance reimbursement; Keck Sourcing creates a Purchase Order, and then the study is approved. For questions about this process, contact Tamara Murphy, Associate Administrator for the Keck Medical Center Supply Chain; Tamara.Murphy@med.usc.edu or 323-442-8325.

 

It is NIH policy that each Institute and Center (IC) should have a system for the appropriate oversight and monitoring of the conduct of clinical trials to ensure the safety of participants and the validity and integrity of the data for all NIH-supported or conducted clinical trials. The establishment of data safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risk to the participants. The data and safety monitoring functions and oversight of such activities are distinct from the requirement for study review and approval by an Institutional Review Board (IRB) (NIH Policy for Data and Safety Monitoring). NIH has policies and guidance regarding data and safety monitoring of clinical trials categorized based on funding source.

In order to ensure appropriate oversite, a clinical trial sponsor or sponsor-investigator should develop a monitoring plan. There are many factors to consider when developing a monitoring plan, including the study design, the types of trial endpoints, the clinical complexity of the study population, the geographical locations of the trial, the experience of the clinical investigators, electronic data capturing, the safety of the investigational product, the stage of the trial, and the quantity of data. The monitoring plan should include specific details like who the monitor will be, responsibilities of the monitor, frequency of monitoring, types of monitoring that will be performed, the activities of monitoring at each visit, and how various monitoring activities will be documented. The monitoring plan should also detail what is to be monitored, including documents, equipment, personnel, and other items that are relevant to the study. The plan should focus on ways to reduce site errors and minimize risks associated with critical data and processes to ensure proper study conduct (Oversight of Clinical Investigations — A Risk-Based Approach to Monitoring, FDA Guidance Document).

If you would like to learn more about monitoring or for access to a monitoring plan template, monitoring SOPs and checklists please:

  1. Go this website
  2. Click create new account (right-hand side)
  3. Type in your details and click Create my new account (bottom of page)
  4. Open your email that comes when you create your account
  5. Click the link to confirm your account
  6. Click Courses (middle of page)
  7. Scroll down (a little) and click Module 1 – Clinical Trial Monitoring
  8. Click Enroll me (middle of page)

A Data and Safety Monitoring Committee (DSMC) is an independent body established by the sponsor to review data from an ongoing clinical trial. It is also known as a Data Monitoring Committee (DMC) or a Data and Safety Monitoring Board (DSMB). A DSMC advises the sponsor regarding the safety of trial subjects as well as the validity and scientific merit of the trial. The members are typically specialists who can assess the safety and efficacy of the results and make recommendations to continue, modify, or stop a trial. Unlike clinical trial monitors, the members of a DSMC do not oversee quality control of clinical trial sites.

USC’s Clinical Investigations Support Office (CISO) has an ongoing DSMC that regularly evaluates all cancer studies. 

ClinicalTrials.gov is a federal database for all publicly and privately supported clinical studies of human subjects conducted around the world. The FDA Amendment Act (FDAAA) of 2007 requires responsible parties in applicable clinical trials to register trials and submit summary results to ClinicalTrials.gov. Per recent NIH changes to the clinical trial policy, all studies (IITs and sponsored) that meet the NIH definition of a clinical trial must be registered.

For assistance with ClinicalTrials.gov registration or reporting, contact Jean Chan at jeanbcha@usc.edu or 213-821-7134.

In addition to the FDA, some funding agencies may require registration. The site is a resource to patients who are seeking to participate in clinical trials, and helps ensure that null studies (studies with negative results) are published. Study subjects must be informed in the consent document that clinical trial information will be submitted to the National Institutes of Health/National Library of Medicine (NIH/NLM) for inclusion in the clinical trial registry databank. 

It is the sponsor’s responsibility to register clinical trials when they begin, provide timely updates, and submit summary results to clinicaltrials.gov. Sponsor-investigator trials must be registered by the PI. “Applicable Clinical Trials” include:

  • Drugs and biologics trials– clinical investigations, other than phase I clinical investigations, of drugs or biological products subject to FDA regulation
  • Device trials – trials with health outcomes of devices subject to FDA regulation, other than small feasibility studies, and pediatric postmarket surveillance required by FDA http://clinicaltrials.gov/

Federal regulations require that subjects be provided with any significant new information or findings obtained during the course of the research that may affect a subject's willingness to continue participation. The IRB requires that all previously-enrolled subjects be provided with the new information in a revised consent form. The IRB must review and approve the revised consent and any protocol changes prior to implementing changes. When study changes are necessary to eliminate apparent immediate hazards to subjects, they may be implemented prior to IRB approval but must be reported to the IRB.

The revised consent form must clearly provide new information and document the participant’s decision to remain in the study.

Examples of situations that may require you to provide new information to subjects are as follows:

  • Changes to the procedures that may affect a subject’s willingness to continue in the research
  • Identification of new risks or that risks previously described are known to occur with greater frequency or severity than previously reported
  • Significant changes in costs to subjects
  • New conflict of interest for a researcher
  • Notification of findings from this study or related studies

In accordance with federal regulations, the USC IRB requires that ongoing greater than minimal risk research protocols undergo continuing review at intervals appropriate to the degree of risk, but not less than once per year. The frequency and extent of continuing review for each study is based upon study type, risk, uniqueness of procedures, and vulnerability of subjects.

The continuing review application (in iStar) involves updates on the items requested in the initial submission, including any adverse events and any changes in number of subjects. Continuing review affirms that the study continues to sufficiently protect subject safety and welfare and that documentation of the study is complete, accurate, and up-to-date. More details about exactly what is required for continuing review can be found in USC HSPP Policies and Procedures – 7.12.

A full list of contact information including phone number and email addresses for relevant entities pertaining to clinical research at USC is provided at this link. The list is divided by topic and contains the contact information of many relevant offices. 


Have questions or updates? Let us know!

Email CRS@sc-ctsi.org

NIH Funding Acknowledgment: Important - All publications resulting from the utilization of SC CTSI resources are required to credit the SC CTSI grant by including the NIH funding acknowledgment and must comply with the NIH Public Access Policy.