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 – 3-4743 roseann.talarico@jefferson.edu• Most are negotiated within 5-10 business days• Include the name, address, telephone number and the

Sponsor/CRO email/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 OperationsCoverage 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

Day 1 Day 8Day 15

Day 22

Day 43Day 50

Day 57

Day 64

N/A No S This is not a billable item or service.N/A No S This is not a billable item or service.N/A No S This is not a billable item or service.N/A No S S S S S S S S S This is not a billable item or service.N/A No S S S S S S S S S This is not a billable item or service.

99201 - 99205; 99211 - 99215

G0463

Q1 M M M According to the NCCN Clinical Practice Guidelines in Oncology Multiple Myeloma Version 2.2014 "NCCN Guidelines" a physical exam is considered conventional care at workup (NCCN Guidelines, p. 6). Patients in this trial have a confirmed diagnosis of relapsed/refractory multiple myeloma after treatment with at least two different previous regimens. Prior treatment must include at least two standard anti-myeloma therapies or induction therapy followed by autologous stem cell transplant (Protocol, p. 23). The study drug given in this trial has unknown side effects. A physical exam at screening, once per cycle and at response assessments appear reasonable and necessary for the clinical management of the patient in order to monitor disease progression and potential side effects. Coverage supported by NCD 310.1.

N/A No NA NA NA NA NA NA NA NA NA This is a bundled service, and is not billable.

N/A No NA NA NA NA NA NA NA NA NA This is a bundled service, and is not billable.

N/A No NA This is a bundled service, and is not billable.

85025 or

85027 and 85007

Q1 M M M M M M M M M A CBC with differential is considered conventional care at initial workup (NCCN Guidelines, p. 6). The study drug, ALT-803, caused an increase in white blood cell counts in animal studies (Protocol, p. 18-19). Patients in this trial have multiple myeloma which also affects blood counts. CBC testing throughout treatment appears to be done both for the clinical management of the patient and to monitor, assess and treat for potential complications associated with the study drug. Coverage supported by NCD 310.1 and NCD 190.15.

80053 Q1 M M M M M M M M M The study drug, ALT-803, caused a decrease in total protein and albumin levels in the blood, as well as decreased blood calcium levels in animal studies (Protocol, p. 18-19). CMP testing throughout treatment appears to be done both for the clinical management of the patient and to monitor, assess and treat for potential complications associated with the study drug. Coverage supported by NCD 310.1.

93000 - 93010 No S S S The study drug does not appear to have cardiac side effects, and states that "no dose related abnormalities based on ECG or ophthalmic evaluations were

J9999 Q0 NB NB NB NB NB NB NB NB The study drug will be provided by the sponsor. The protocol states: "ALT-803 is an investigational drug supplied to investigators by the Altor Bioscience Corporation at Miramar, Florida. Sufficient study drug will be available for this protocol to treat all of

96365-96368 Q1 M M M M M M M M IV administration of the study drug is supported by NCD 310.1.

Study Medications

Comprehensive Metabolic Panel

Medical History

Time & Effort

Concomitant MedicationsAdverse Event Assessment

Evaluation & Management Services

Vital Signs

Complete Physical Exam

M: Medicare or Other Heath PlanS: Charged to Study Fund or SponsorNA: Bundled With Another Payment From Third PartyNB: Not Billed to Anyone, Not a Billed Event, No CPT Code

ALT-803 (IV)

Scans/Procedures

CBC with Differential

Electrocardiogram (EKG)

Coverage Code Key

Informed ConsentInclusion/Exclusion Criteria

Comments

IV Infusion (ALT-803)

Labs

Weight

Height

Items and ServicesCPT/HCPCS

Codes Q1/Q0 Mod

Screening1 Month 1

Cycle 1

Month 2

Cycle 2

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

Activity Charge Hours PI hours RC hoursStudy Feasibility Assessment (database review, medical records, recruiting/advertising preparation) 525.41$ 8.00 1.6 6.4Site Qualification Visit preparation and attendance 247.23$ 4.50 0.45 4.05Regulatory Documents Preparation, Submission, Collecting Signatures (FDA 1572, CVs, W9, etc) 933.99$ 17.00 1.7 15.3IRB Documents Preparation, Submission, Collecting Signatures, Queries (Proposal Transmittal, Informed Consent, etc) 836.11$ 16.00 1.2 14.8Source Document Creation 1,326.15$ 30.00 0 30.00Site Initiation Visit preparation and attendance 604.35$ 11.00 1.1 9.9PI Staff Meetings, Training, Hiring, Communications 520.51$ 10.50 0.525 9.975Total admin start up 4,993.74$ 97.00 6.575 90.425Hourly Rate + 26.3% fringe Hourly w/ FringePI (weekly salary / 40 hours) 120.00$ 151.56 Research Coordinator (weekly salary / 40 hours) 35.00$ 44.205

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

Recruitment Reconsent Fee Pharmacy Start Up Amendment Administrative FeePharmacy Monthly Maintenance Study Close-OutPharmacy Close Out Document Storage

IRB Submission Work on Continuing and Ammendments Site Monitor Visit FeeUAE Submission to IRB (FDA required 24-48 hours) Sponsor/FDA auditIND Safety Reports (Per Report) Dry IceAdvertising Equiptment/Supplies

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

Day 1 Day 8Day 15

Day 22

Day 43Day 50

Day 57

Day 64

N/A $150 $150 $150N/A $100 $100 $100N/A $75 $75 $75N/A $50 $50 $50 $50 $50 $50 $50 $50 $50 $50 $450N/A $50 $50 $50 $50 $50 $50 $50 $50 $50 $50 $450

99201 - 99205; 99211 - 99215

G0463

Q1 M M M M

N/A No NA NA NA NA NA NA NA NA NA NA

N/A No NA NA NA NA NA NA NA NA NA

N/A No NA

85025 or

85027 and 85007

Q1 M M M M M M M M M M

80053 Q1 M M M M M M M M M M

36415 or 36592 Q1 M M

93000 - 93010 $130 $130 $130 $130 $390

J9999 No NB NB NB NB NB NB NB NB

96365-96368 Q1 M M M M M M M MN/A $150 $150 $150 $150 $150 $150 $150 $150 $150 $150 $1,350

N/A $150 $150 $150 $150 $150 $150 $150 $150 $150 $150 $1,350$855 $530 $400 $400 $400 $530 $400 $400 $400 $4,315$257 $159 $120 $120 $120 $159 $120 $120 $120 $1,295

$1,112 $689 $520 $520 $520 $689 $520 $520 $520 $5,610

Concomitant MedicationsAdverse Event Assessment

Vital Signs

Comprehensive Metabolic Panel

Medical History

Time & Effort

Complete Physical Exam

Venipuncture

Month 2

Cycle 2

Cost Screening1 Month 1

Cycle 1

Indirect Rate 30%Total Costs

Total

IV Infusion (ALT-803)

Weight

Height

Items and ServicesCPT/HCPCS

Codes

Informed ConsentInclusion/Exclusion Criteria

PI

Study CoordinatorTotal Direct Costs

ALT-803 (IV)

CBC with Differential

Electrocardiogram (EKG)

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 email 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

Study name FAKE Date established 9/8/2014PI Dr. Joseph Smith ORA Account No.080-18014-J97801Sponsor: ABC Pharmaceutical Sponsor contact nameCoordinator Paul Jones Sponsor contact emailNotes:

-$ Screening/ Baseline

Visit 1: Hour 6

Visit 2: Hour 12

Visit 3: Hour 24

Visit 4: Hour 48

Visit 5: Hour 72

Visit 6: Hour 96 Visit 7: Discharge TOTAL

$2,754.00 $2,793.00 $1,700.00 $1,265.00 $1,870.00 $1,192.00 $1,076.00 $1,261.00 $13,911.00

$2,503.64 $2,539.09 $1,545.45 $1,150.00 $1,700.00 $1,083.64 $978.18 $1,146.36 $12,646.36$577.76 $585.94 $356.64 $265.38 $392.31 $250.07 $225.73 $264.55 $2,918.39

$1,925.87 $1,953.15 $1,188.81 $884.62 $1,307.69 $833.57 $752.45 $881.82 $9,727.9722.98 23.31 14.19 10.56 15.61 9.95 8.98 10.52 116.1032.49 32.42 19.73 14.68 21.70 13.84 12.49 14.64 161.98

Subject NameSubject ID DOB W9 (Y/N) MRN

Screening/ Baseline Visit 1 Visit 2 Visit 3 Visit 4 Visit 5: Visit 6: Visit 8 Notes (Indicate any visit activities not performed

Patient Payments

Subject NameSubject ID

Screening/ Baseline

Visit 1 Visit 2 Visit 3 Visit 4 Visit 5: Visit 6: Visit 8

Total Expected Realtime payment

Total 10% holdback due

at study completion

Total Payment

0 0 -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ 0 0 -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ 0 0 -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ 0 0 -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ 0 0 -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$

Total Expected Realtime payment

-$

Total 10% holdback due at study completion

-$

Total Payment-$

# Hours (CRC)

Payment less 10% holdback (holdback received upon closure of

study)

Grand Total A/R

PaymentSubject Log

Indirect (30%)Real Payment

# Hours (CRN)

Subject ID Date of Visit Amount to Be Invoiced Subject ID Date of Visit Amount to Be Invoiced-$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$

Total: -$ Total: -$

TOTAL Requiring Action -$

Unscheduled Safety Visit Discharge Visit

Additional Forms

Date Invoice Amount Date Invoice Amount Date Invoice Amount7/2/2015 2,000.00$ 2/12/2015 1,500.00$ -$

-$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$ -$

Total 2,000.00$ Total 1,500.00$ Total -$

-$

Continuing Review Amendment (Full) Amendment (Expedited)

TOTAL Requiring Action:

IRB Activity

Date Amount9/15/2014 16,550.00$ 7/17/2015 8,850.00$ Pre-screening for 107 subjects, IRB Continuing review, IRB amendment

Invoices SubmittedCommentElectronic data capture, study start-up fee, administration fee, medicare analysis fee, Initial IRB fee

Invoices Submitted

Total outstanding patient payment expected realtime 1,000.00$

Payments received (Patient Visits-Main Study) Total 10% holdback due upon study completion 9.09$ Date Check # Amount Notes Total patient A/R 1,009.09$

3,018.18$

-$ Total patient payments received

Invoiced per Additional FormsDate Invoice # Amount Notes

-$ Total patient payments received-$ Total patient payments received

Invoiced per IRBDate Invoice # Amount Notes

7/17/2015 J97801-RM-2015-2 3,500.00$

3,500.00$ Total patient payments received

Financial Summary of A/R

Grand Total Study A/R (or Items requiring Invoicing)

Financial Summary of Accounts Receivable

Clinical Research Coordinator Role

• Communication with your JCRI Clinical Research Administrator is key

• Email 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, 3-3311

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, 5-2521

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 vendorshttp://www.jefferson.edu/content/dam/tju/finance/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, 3-2127• Michael Caggiano, Team Lead, 3-4746• Jennifer Lott, Team Lead, 5-2546• Jason Salvatore, Senior Research Administrator Contracts,

3-2011• Ann Hastings, Research Administrator Contracts, 3-5645• Jenny Campbell, Clinical Research Administrator, 3-4282• LouEllen Daniel, Clinical Research Administrator, 3-5390• Ryan Massimilla, Clinical Research Administrator, 3-2890• Mary Rose Taft, Clinical Research Administrator, 3-4265