The Business Operations of Clinical Research Trials, From Start to Finish

The Preaward Process

Confidentiality Agreements One Way A company may want to send a protocol to the Principle Investigator (PI) so that he/she can decide whether to participate in the trial The protocol will have confidential information that the company needs to safeguard The sponsor may wish to support a Principal Investigator by supporting travel to a conference which may have confidential information Two Way (Mutual) or One Way Out A Principal Investigator may want to request a sponsor to support their own research

How does this work? Principal Investigator contacts University administration looking for assistance Sponsor contacts PI/Coordinator Sponsor contacts University administration In order to protect the University and the PI, all CDA’s require University signature Each must be reviewed, negotiated and executed by the PI, University Official and the Company.

Negotiation CDA’s are usually straightforward and require little negotiation Point of contact: Roseann Talarico – Most are negotiated within 5-10 business days Include the name, address, telephone number and the Sponsor/CRO /phone If needed, include a note with any concerns about the CDA or what confidential information University may wish to protect Once completed PI will receive executable copy – return to complete the execution process Fully executed copy sent to PI for recordkeeping

What is required to begin the business process? Key indicators Fully executed CDA Cancer Center MDG/PRC approvals Department staff/coordinator provides documents to business office Electronic Proposal Transmittal Form (ePTF) is created What is the (ePTF) and what is it for? Electronic mechanism for Jefferson to manage, maintain, and approve all research Grants Contracts

What forms are required? Materials required to complete (ePTF) for the first round approval Protocol Draft Informed Consent (ICF) Clinical Trial Agreement (CTA) Sponsor Budget

First round approval Department administrator/PI/Chair approve MCA/contract/budget negotiation process begins Second round approval MCA/contract/budget negotiated IRB approved Department administrator/PI approve Execution of contract/account set up What is the approval process?

JCRI Business Operations Coverage Analysis & Budget

Coverage Analysis

Materials needed to conduct a Coverage Analysis From Study Team: Same as (ePTF) process Protocol Draft Informed Consent (ICF) Clinical Trial Agreement (CTA) Sponsor Budget Approved electronic proposal transmittal form (ePTF) First round only

What is a Coverage Analysis? Document that determines the appropriate payor (i.e. Sponsor, Medicare or third party payor) for each item and service required by a clinical research trial

Why is a Coverage Analysis important? Reduces risk for submitting false claims Billing for services not part of a qualifying clinical trial Billing for items and services promised/paid for by Sponsor Billing for research only items and services Assists in budget negotiations with Sponsor/CRO Identifies costs that need to be accounted for in the sponsor budget Basis of billing compliance/audits Provides evidence of due diligence and a mechanism for compliance with billing rules

Coverage Analysis Process Receive all materials from the study team Create a grid that reflects all clinical events and time points in the protocol Review clinical guidelines along with CMS national and local coverage determinations to identify the appropriate payor for each event Send the CA to PI/SC for review and approval Approve or revise the CA as necessary

Clinical Trial Budget

Develop a financial plan that encompasses all phases of the study: Start-up costs Institutional costs Other costs incurred throughout the study Subject costs

Develop a financial plan that encompasses all phases of the study: Start-up costs training, meetings, IRB/regulatory work, source document creation Institutional costs Other costs incurred throughout the study Subject costs

Start-Up Costs

Develop a financial plan that encompasses all phases of the study: Start-up costs training, meetings, IRB/regulatory work, source document creation Institutional costs F&A, IRB fees, billing compliance fees Other costs incurred throughout the study Subject costs

Develop a financial plan that encompasses all phases of the study: Start-up costs training, meetings, IRB/regulatory work, source document creation Institutional costs F&A, IRB fees, billing compliance fee WIRB/Quorum – One time fee $2,500 Other costs incurred throughout the study site monitor fees, IRB work on continuing reviews or amendments, dry ice, close-out costs, etc. Subject costs

Other Costs

Develop a financial plan that encompasses all phases of the study: Start-up costs training, meetings, IRB/regulatory work, source document creation Institutional costs F&A, IRB fees, billing compliance fee WIRB/Quorum – One time fee $2,500 Other costs incurred throughout the study site monitor fees, IRB work on continuing reviews or amendments, dry ice, close-out costs, etc. Subject costs Any items that are not billable to insurance or provided by the sponsor

Accomplished by considering all stakeholders input: PI and Study Coordinator Radiology Pathology Pharmacy Hospital Billing Professional Services Billing Other departments Sponsor

Clinical Trial Agreement

What is required to complete a contract? Who wrote the protocol? Sponsor Clinical Trial Agreement PI/Jefferson Investigator Initiated Agreement Is the sponsor contract new or previously negotiated? If new – review/red line changes Forward to legal If previously negotiated – similar protocol Review/red line changes Forward to sponsor

What is required to complete a contract? Negotiate terms Ensure budget, billing and payment terms are acceptable Is the IRB approved? Approval letter and informed consent reviewed Sponsor and protocol must match contract Subject injury and indemnification language Different terms in each but intent must be the same (ePTF) secondary approvals

What is required to complete a contract? Execute Forward to PI Return to sponsor PDF or mail Account set up Establishment letter to staff and accounting MCA includes account number sent to staff and billing

Post Account Establishment Modifications/Amendments No cost extension Change in PI Modification to protocol No budget modification Modification to protocol Budget modification $5,000 or greater (ePTF) supplement Approvals, etc. Follow same SOPs as a new clinical trial

PI: I developed and created my own protocol and I want to send it to Sponsor for review to determine whether they would consider funding this very important project for my study. Should I just send it to their scientist for review as is?

PI: I just received an from sponsor requesting that I sign the attached CDA so that they may immediately send the protocol and regulatory documents for review. This will allow me the opportunity to begin the process on this very lucrative study. May I just sign it and return this as is? I don’t have time to waste.

PI: I just signed the required and negotiated CDA by sponsor and the university. They subsequently sent me the protocol, budget, and sample informed consent. I just checked my stock portfolio and realize that my wife and I each have a few shares of sponsor stock equating to approximately $6,000 each. When I approve the e-PTF is it necessary for me to mark that I have a conflict since I only have around $6,000 of stock as its below the threshold? Am I correct?

PI: I just signed the required CDA by sponsor and they subsequently sent me the protocol, budget, and sample informed consent. I happen to be on the scientific advisory board of this sponsor. When I approve the ePTF is it necessary for me to mark that I have a conflict since I only volunteer on this board. Am I correct?

PI: The budget and contract are negotiated and ready to sign. IRB is still pending. Is it acceptable to fully execute the contract prior to IRB approval?

PI: The Office of Research Administration requires what 4 (four) items to be submitted to your Clinical Research Administrator representative in order to begin contract and budget negotiation process?

PI: I just signed the CDA with sponsor and they just sent me their protocol, budget, and consent document. This study is so right for me and I can accrue quite a number of subjects. The administrative process at TJU takes so long. How can I minimize the timelines so that I can start accruing subjects as quickly as possible?

How to initiate the process Please, please, and please one more time reach out to your clinical research administrator for more information. Contact information provided at the end of the post award session

JCRI Business Operations – Post-Award

Processes relating to the collection of sponsored clinical trial funding

Invoicing Clinical Research Administrator submits invoices to the sponsor Initial invoice includes startup fees, initial IRB fees, billing and compliance and any other items listed in the clinical trial agreement Ongoing invoices include IRB fees & IRB prep fees, pharmacy monthly maintenance, site monitor fees, advertising, protocol specific procedures, other items listed in clinical trial agreement

Milestone Payments Based on finalized contract, milestone payments would apply if TJU is paid upon enrollment of a certain number of patients, completion and collection of case report forms, etc.

Patient Tracking Study calendar set up based on finalized budget Calculates amounts due based on the patient activity within the study May include conditional procedures or services, based on the study

Additional Forms

IRB Activity

Invoices Submitted

Financial Summary of Accounts Receivable

Clinical Research Coordinator Role Communication with your JCRI Clinical Research Administrator is key copies of IRB approval letters, documentation for advertising and any other supporting documents for invoicing Ensure patient trackers are updated timely Ask questions to your Clinical Research Administrator

Clinical Research Administrator should receive all clinical trial payments from the sponsor Patient payments paid via CRF Payment entered as received on patient payment sheet Payments reconciled against visits on patient visit sheet. BOPS ensures payments received match the amounts expected from the sponsor.

Clinical Research Coordinator’s Role Any payments received related to a clinical trial by the research staff should be forwarded to your Clinical Research Administrator for deposit and proper accounting Be prepared to answer questions from the Clinical Research Administrator about patient activity

Ensures that studies are billed for research specific procedures

Clinical Trial Billing Entities Jefferson University Physicians (JUP) Bills related to clinical services sent monthly from JUP Business Services Hospital Bills related to clinical services sent regularly from Hospital Business Services

Jefferson University Physician (JUP) Bills -Physician professional fees -Examples: Physical exam, evaluation of MRI, ECG interpretation, etc. -Services get billed to grant or patient’s insurance for JUP services. Review billing and compliance grid as reference -Contact for JUP Billing - Merle Charlton,

Hospital Bills Technical Fees for clinical trial services i.e. MRI cost, CT scan cost, some clinical labs, ECG cost, etc. Billed to grant or patient insurance as designated by billing and compliance grid Contact for hospital billing Ed Dunigan,

Clinical Research Coordinator’s Role Keep the billing and compliance grid available Be prepared to answer questions your Clinical Research Administrator may have

Request for Payment form (RFP) Petty cash Check payments Payments to vendors ance/form_center/Request_for_Payment_TJU.pdf

Payments to Patients For payments made to patients, as compensation for study related activities in the form of petty cash an RFP will be submitted to your Clinical Research Administrator For check payments, the Request for Payment will be submitted to your Clinical Research Administrator for approval

Payment to Vendors Use Request for Payment form, enter vendor information in the address section, attach any invoices and be sure to check box for this to be included with the check. Forward the RFP to your Clinical Research Administrator for approval

Clinical Research Coordinator’s Role Ensure you’ve included all information on the Request for Payment and attached any required documentation Be prepared to answer questions or provide information to your Clinical Research Administrator

Contact Information Ronald Polizzi, Director, Business Operations JCRI, Michael Caggiano, Team Lead, Jennifer Lott, Team Lead, Jason Salvatore, Senior Research Administrator Contracts, Ann Hastings, Research Administrator Contracts, Jenny Campbell, Clinical Research Administrator, LouEllen Daniel, Clinical Research Administrator, Ryan Massimilla, Clinical Research Administrator, Mary Rose Taft, Clinical Research Administrator,