Office of Clinical Research

PI is approached by Sponsor for study consideration

PI needs to determine if there are:

• Necessary equipment to run the study per protocol
• Sufficient staff support
• Available cohort of patients needed for the study

Sponsor requires a Confidentiality disclosure agreement (CDAs) to be signed before protocol is provided

CDAs to enable review of protocols from companies are reviewed by an Office of General Counsel lawyer and signed by the Executive Director in ORSS and/or the Principal Investigator (based on sponsor’s requirements).

Confirm Feasibility

Make determination to proceed after considering the following:

• Estimate accrual based on existing cohort size at Penn
• Ancillary resource needs
• Site and space
• Personnel time
• Review study timeline and subject follow-up expectations with Sponsor and study team
• Some sponsors may come out to Penn for a pre-study site visit.

Study Feasibility Assessment

Cohort determination

Ancillary Resources

Obtain all protocol information from sponsor

Obtain protocol, case report forms, investigational product information, monitoring plans, logs, etc. This material is referred to altogether as the Regulatory Binder or Study Administrative File.

Budget Evaluation
[See also: Step 4]

Budget Example

Review all elements needed for submission, such as:

• Protocol
• ICF & HIPAA
• Investigator“s Brochure
• *Case Report Forms
• CVs and other licensure information
• Recruitment materials

Make sure that all applicable parties are included, such as:

• IRB
• CTSRMC for cancer-related protocol*
• Pharmacy or Laboratory
• CAMRIS/CACTIS/RDRC
• Other Ancillary Committees

Elements of Informed Consent Form

ICF Template

Submitting to the IRB (Initial Review)

CTSRMC

Ancillary Resources

* Obtain UPCC Number

Cancer-related protocols require a UPCC# in addition to an IRB#. PennCTMS (commonly referred to as Velos) is the Clinical Trials Management System (CTMS) for all cancer-related trials. You will need access to PennCTMS to submit a cancer-related protocol for initial review.

• Complete PennCTMS training to obtain an account
• Register your study in the system to obtain a UPCC#

PennCTMS Training Information

The PI must play a role in the ongoing monitoring and oversight of his/her protocol. If the protocol is cancer-related, a Monitoring Plan must be submitted to the DSMC to gain CTSRMC approval.

If a Medical Monitor will monitor the protocol, s/he cannot also be the PI.

Budget building and negotiation

Budget negotiation may be the responsibility of the investigator, CRC, BA or other research staff; budget approval is the responsibility of the business office.

• Include ancillary service costs into budget negotiations (i.e.: IDS, CHPS, imaging services)
• Cost Finder can be a helpful tool to see the actual cost of the services to determine the price given to sponsors

Cost-Finder

To obtain access to the Cost-Finder system, register with the Clinical Research Registry

Contact OCR if you would like assistance with budget development

Review protocol procedures for standard of care vs. research

Standard of care means: usual and reimbursable cost. Sponsors will often provide reimbursement language in the contract.

The study team (CRC/BA/PI) is responsible for providing an accurate assessment by filling out the Prospective Reimbursement Analysis (PRA).

Prospective Reimbursement Analysis (PRA) Form

See Below for summary of CRC/BA co-responsibilities

Use of Device in the OR

If the protocol involves the use of an investigational agent/device within the Operating Room, please contact surgical services.

Contact:
Associate Executive Dir.
Surgical Services UPHS
215-662-2089

Financial Disclosure

FIDES is a web-based application to report financial interests and relationships related to participation in specific research projects.

• Intellectual property interests
• Fiduciary Responsibilities
• Equity Interests
• Extramural Activities

It is recommended that you notify OVPR once this is finalized.

FIDES

For Help e-mail: OVRP

Contract

Non-budget contractual terms are negotiated by CTCU; requests are submitted via a parallel review form; once non-budget terms and budget are negotiated and internal school approvals are obtained, the contract is signed.

For additional information contact CTCU.

Request Research Billing Number (RBN)

Establish billing procedures

• Obtain account numbers to track standard of care accounting for billing purpose.
• Prepare study budget as per sponsor agreement for payment milestones.

Request RBN

Assure that all paperwork is completed, submitted, and filed appropriately

Keep regulatory files in a secure area per Sponsor requirement. Sponsors usually provide information on how they want the regulatory binder organized.

Determine the following:

• Schedule of correspondence
• Preferred method of contact
• Documentation expectations

Study Document Management

Site initiation visit (SIV)

This can be an on-site visit, or an investigator meeting.

Monitoring Activities list- including Site Initiation Visit

Study supplies/drug/device

If the Sponsor has agreed to provide supplies/drug/device, they will be shipped around the time of study activation. Make sure the space is secure and meets the requirement for storage (light/humidity/temperature, etc).

• Discuss process for re-supply with Sponsor
• Destruction procedures

Investigational Product Management if not using IDS

Complete site training

Copy and distribute all relevant study materials to study personnel  as defined in the Delegation of Responsibility Log

Delegation of Responsibility and Signature Log

Protocol training

Develop a training agenda for study staff not trained by the sponsor. Document training.

• Pharmacy and Laboratory
• Ancillary staff
• Clinical staff

Protocol training Log

Screen and Recruit Subjects
Obtain Consent

Sites should have agreed upon screening method.

• Develop and follow patient consent process
• Consent should be reviewed and given to potential participants early in the process
• No study-specific procedures may take place until the ICF is signed.

Screening Guidelines

Consenting, Screening, and Enrollment

Screening and Enrollment Log

Maintaining a Subject File

Subject follow-up

The time and procedures for subject follow-up will be determined by the study protocol’s endpoints. All follow-up assessments and documentation should be completed, recorded, and sent to Sponsors per protocol. Re-consent as needed.

Re-consenting

Lost-to-follow up and re-contacting

Subject Payment

Submit subject remuneration/ reimbursement to BA in a timely manner. Document payment submission.

Subject Payment Procedures

Adverse Event (AE)/Serious Adverse Event (SAE) Management

Procedures for handling AE and SAE will vary by Sponsor. Make sure you know of the proper reporting process for your study.

• Some Sponsors ask that you report AE/SAE to CRO instead of them directly.
• Report to IRB and other reviewing entities per protocol
• All DSMC reportable events must be entered into PennCTMS

AE log for protocol

AE log for individual subject

IRB guidance for reportable events

Monitoring

The Sponsor may send a Study Monitor (also known as a CRA) periodically to review and assess the progress of the study.

Monitoring Activities

Annual Review

Most reviewing entities require that you submit a Continuing Review form annually. Submit items to Sponsor/CRO before submitting to IRB and other reviewing entities.

Continuing Review-Renewal of Projects

Protocol Modification

Modifications can range from changes in the primary or secondary outcomes, changes in follow-up procedures. Or just the addition/removal of staff. Distribute submissions and final approvals to all relevant reviewing entities, staff, and Sponsor contacts.

Submitting Modification/Amendments.

Modification- how to submit to the IRB.

Deviation

Deviations are a one-time, unintentional action that does not follow the protocol. Sponsors may have their own reporting requirements. Forward all documentation to relevant reviewing entities.

Determine whether or not a protocol amendment is needed to prevent further deviation.

Documentation and Reporting Deviations

Deviation - how to submit to the IRB.

If the deviations compromise the safety and welfare of subjects, it must be reported within 10 business days to the IRB.

Exception

Exceptions are a one-time, intentional action that does not follow the protocol but is approved by the IRB prior to the occurrence. Speak to your sponsor first before submitting an exception to the Penn IRB. Circulate to all relevant reviewing entities and study staff members.

Exception – how to submit to the IRB.

• Schedule close-out visit with Sponsor/CRO.
• Obtain IRB termination letter and forward to Sponsor and relevant reviewing entities.
• Work with BA to develop content for the financial component of a study close-out.

Study Closure Procedures

Closeout Checklist

Investigational Product Management

Complete Investigational Product inventory assessment.

• Reconcile discrepancies.
• Return or destroy product/supplies according to Sponsor/CRO instructions.

IP Management if not using IDS

Document Collection and Archiving

The University Records Center provides a service to dispose or store research study documents.

• Create a written inventory of all items to be stored