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
What is the approval process?
• 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
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
Items and Services
CPT/HCPCS
Codes
Time & Effort
Informed Consent
N/A
Inclusion/Exclusion Criteria
N/A
Medical History
N/A
Concomitant Medications
N/A
Adverse Event Assessment
N/A
Evaluation & Management Services
Complete Physical Exam
99201 - 99205;
99211 - 99215
G0463
Cycle 1
Month 1
Day
Day 1 Day 8
15
Q1/Q0
Mod
Screening1
No
No
No
No
No
S
S
S
S
S
S
S
Q1
M
M
S
S
S
S
Cycle 2
Month 2
Day
Day Day
Day 43
Day 64
22
50
57
S
S
S
S
S
S
S
S
S
S
This
This
This
This
This
is
is
is
is
is
not
not
not
not
not
a billable item
a billable item
a billable item
a billable item
a billable item
or service.
or service.
or service.
or service.
or service.
Vital Signs
N/A
No
NA
NA
NA
NA
NA
NA
NA
NA
NA
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 antimyeloma 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.
This is a bundled service, and is not billable.
Weight
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
85025
or
85027 and 85007
Q1
M
M
M
M
M
M
M
M
M
80053
Q1
M
M
M
M
M
M
M
M
M
93000 - 93010
No
S
S
J9999
Q0
NB
NB
NB
NB
NB
NB
NB
NB
96365-96368
Q1
M
M
M
M
M
M
M
M
Height
Labs
CBC with Differential
Comprehensive Metabolic Panel
Scans/Procedures
Electrocardiogram (EKG)
Study Medications
ALT-803 (IV)
IV Infusion (ALT-803)
Coverage Code Key
M: Medicare or Other Heath Plan
S: Charged to Study Fund or Sponsor
NA: Bundled With Another Payment From Third Party
NB: Not Billed to Anyone, Not a Billed Event, No CPT Code
M
Comments
This is a bundled service, and is not billable.
S
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.
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.
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
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
IV administration of the study drug is supported by NCD 310.1.
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
Study Feasibility Assessment (database review, medical records, recruiting/advertising
preparation)
Site Qualification Visit preparation and attendance
Regulatory Documents Preparation, Submission, Collecting Signatures (FDA 1572, CVs, W9,
etc)
IRB Documents Preparation, Submission, Collecting Signatures, Queries (Proposal
Transmittal, Informed Consent, etc)
Source Document Creation
Site Initiation Visit preparation and attendance
PI Staff Meetings, Training, Hiring, Communications
Total admin start up
Hourly Rate + 26.3% fringe
PI (weekly salary / 40 hours)
Research Coordinator (weekly salary / 40 hours)
Charge
Hours
PI hours RC hours
$
$
525.41
247.23
8.00
4.50
1.6
0.45
6.4
4.05
$
933.99
17.00
1.7
15.3
$
$
$
$
$
836.11
1,326.15
604.35
520.51
4,993.74
16.00
30.00
11.00
10.50
97.00
1.2
0
1.1
0.525
6.575
Hourly
w/ Fringe
$ 120.00
151.56
$ 35.00
44.205
14.8
30.00
9.9
9.975
90.425
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
Pharmacy Start Up
Pharmacy Monthly Maintenance
Pharmacy Close Out
IRB Submission Work on Continuing and Ammendments
UAE Submission to IRB (FDA required 24-48 hours)
IND Safety Reports (Per Report)
Advertising
Reconsent Fee
Amendment Administrative Fee
Study Close-Out
Document Storage
Site Monitor Visit Fee
Sponsor/FDA audit
Dry Ice
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
CPT/HCPCS
Codes
Cycle 1
Month 1
Day
Day 1 Day 8
15
Cycle 2
Month 2
Day
Day Day
Day 43
Day 64
22
50
57
Cost
Screening1
N/A
N/A
N/A
N/A
N/A
99201 - 99205;
99211 - 99215
G0463
N/A
$150
$100
$75
$50
$50
Q1
$150
$100
$75
$50
$50
M
$50
$50
M
$50
$50
$50
$50
$50
$50
$50
$50
M
$50
$50
$50
$50
$50
$50
No
NA
NA
NA
NA
NA
NA
NA
NA
NA
N/A
No
NA
NA
NA
NA
NA
NA
NA
NA
NA
N/A
85025
or
85027 and 85007
No
Q1
NA
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
93000 - 93010
J9999
Q1
$130
No
M
$130
IV Infusion (ALT-803)
PI
96365-96368
N/A
Q1
$150
Study Coordinator
Total Direct Costs
Indirect Rate 30%
Total Costs
N/A
$150
Items and Services
Time & Effort
Informed Consent
Inclusion/Exclusion Criteria
Medical History
Concomitant Medications
Adverse Event Assessment
Complete Physical Exam
Vital Signs
Weight
Height
CBC with Differential
Comprehensive Metabolic Panel
Venipuncture
Electrocardiogram (EKG)
ALT-803 (IV)
$130
NB
NB
NB
NB
$130
NB
Total
$150
$100
$75
$450
$450
M
NA
M
$390
NB
NB
NB
$150
M
M
M
M
M
M
M
M
$150 $150 $150 $150 $150 $150 $150 $150
$1,350
$150
$855
$257
$1,112
$150
$530
$159
$689
$1,350
$4,315
$1,295
$5,610
$150
$400
$120
$520
$150
$400
$120
$520
$150
$400
$120
$520
$150
$530
$159
$689
$150
$400
$120
$520
$150
$400
$120
$520
$150
$400
$120
$520
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
PI
Sponsor:
Coordinator
Notes:
Date established
9/8/2014
ORA Account
080-18014-J97801
No.
Sponsor contact name
Sponsor contact email
FAKE
Dr. Joseph Smith
ABC Pharmaceutical
Paul Jones
Grand Total A/R
Subject Log
$
Visit 3: Visit 4: Hour
Hour 24
48
Screening/
Baseline
Visit 1:
Hour 6
Visit 2:
Hour 12
$2,754.00
$2,793.00
$1,700.00
$1,265.00
$2,503.64
$577.76
$1,925.87
22.98
32.49
Screening/
Baseline
$2,539.09
$585.94
$1,953.15
23.31
32.42
$1,545.45
$356.64
$1,188.81
14.19
19.73
Visit 1
Visit 1
Payment
Visit 5:
Hour 72
Visit 6:
Hour 96
Visit 7: Discharge
TOTAL
$1,870.00
$1,192.00
$1,076.00
$1,261.00
$13,911.00
$1,150.00
$265.38
$884.62
10.56
14.68
$1,700.00
$392.31
$1,307.69
15.61
21.70
$1,083.64
$250.07
$833.57
9.95
13.84
$978.18
$225.73
$752.45
8.98
12.49
$1,146.36
$264.55
$881.82
10.52
14.64
$12,646.36
$2,918.39
$9,727.97
116.10
161.98
Visit 2
Visit 3
Visit 4
Visit 5:
Visit 6:
Visit 8
Visit 2
Visit 3
Visit 4
Visit 5:
Visit 6:
Visit 8
Payment less 10% holdback
(holdback received upon closure of
study)
Indirect (30%)
Real Payment
# Hours (CRN)
# Hours (CRC)
Subject
ID
Subject Name
DOB
W9 (Y/N) MRN
Notes (Indicate any visit activities not performed
Patient Payments
Screening/
Baseline
Subject
ID
Subject Name
0
0
0
0
0
0
0
0
0
0
$
$
$
$
$
-
$
$
$
$
$
-
$
$
$
$
$
-
$
$
$
$
$
-
$
$
$
$
$
-
$
$
$
$
-
$
$
$
$
$
-
$
$
$
$
$
-
Total
Expected
Realtime
payment
$
$
$
$
$
-
Total 10%
holdback due
at study
completion
$
$
$
$
$
-
Total Payment
$
$
$
$
$
-
$
-
$
-
$
-
Total Expected Realtime
payment
Total 10% holdback due at
study completion
Total Payment
Additional Forms
Subject ID
Unscheduled Safety Visit
Date of Visit
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
Total:
$
Amount to Be Invoiced
Discharge Visit
Date of Visit
Subject ID
-
Total:
TOTAL Requiring Action
Amount to Be Invoiced
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
$
-
$
-
IRB Activity
Continuing Review
Date
Invoice Amount
7/2/2015 $
2,000.00
$
$
$
$
$
$
$
Total $
2,000.00
Amendment (Full)
Date Invoice Amount
2/12/2015 $ 1,500.00
$
$
$
$
$
$
$
Total $ 1,500.00
Amendment (Expedited)
Date Invoice Amount
$
$
$
$
$
$
$
$
Total $
-
TOTAL Requiring Action:
$ -
Invoices Submitted
Invoices Submitted
Date
9/15/2014 $
7/17/2015 $
Amount
Comment
16,550.00 Electronic data capture, study start-up fee, administration fee, medicare analysis fee, Initial IRB fee
8,850.00 Pre-screening for 107 subjects, IRB Continuing review, IRB amendment
Financial Summary of Accounts Receivable
Financial Summary of A/R
Total outstanding patient payment expected realtime
Payments received (Patient Visits-Main Study)
Date
Check #
Amount
$
Notes
-
Total patient payments received
Invoiced per Additional Forms
Date
Invoice #
Amount
$
$
Notes
-
Total patient payments received
Total patient payments received
Invoiced per IRB
Date
Invoice #
7/17/2015 J97801-RM-2015-2
Amount
Notes
$ 3,500.00
$
3,500.00 Total patient payments received
Total 10% holdback due upon study completion
Total patient A/R
Grand Total Study A/R (or Items requiring Invoicing)
$
1,000.00
$
$
$
9.09
1,009.09
3,018.18
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 vendors
http://www.jefferson.edu/content/dam/tju/fin
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, 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