Download Lilly Research Laboratories

David Rosenberg, M.D.
August 28, 1998
1
Lilly Research Laboratories
A Division of Eli Lilly and
Company
Lilly Corporate Center
Indianapolis, Indiana 4628s
317 276.2000
August 28, 1998
David R. Rosenberg, M.D.
Wayne State University
9B University Health Center
Detroit, MI 48201
Dear Dr. Rosenberg:
Lilly Research Laboratories, a division of Eli Lilly and Company ("Lilly"), appreciates having the opportunity to
collaborate with Dr. David R. Rosenberg ("Investigator") and Wayne State University ("Institution") in the Study
entitled "Fluoxetine Versus Placebo in Childhood/Adolescent Depression" (protocol B IY-MC-HCJE ["Protocol"],
which Protocol is incorporated herein by reference) ("Study"). This Agreement sets forth the joint and several
obligations of the Investigator and Wayne State University (hereinafter referred to together as "You" or "Your") and the
obligations of Lilly as the sponsor.
I. YOUR OBLIGATIONS
You agree to assume the following obligations in executing this Agreement:
A.
Conduct of the Study You agree to personally conduct or supervise the Study at Your facility or
institution. You and Your colleagues agree to comply with: all conditions specified in the Protocol and Protocol
amendments, including the statements required by Lilly in Your informed consent document; applicable requirements of
the U.S. investigational new drug ("IND") regulations (Title 21, Part 312.1 I seq.); Good Clinical Practice Guidelines;
the conditions specified in Your Statement of Investigator Form (FD-1572); the approval of Your Ethical Review Board
("ERB"); the Code of Federal Regulations (Title 21, Parts 50 and 56) governing informed consent and ERBs; provisions
of the Generic Drug Enforcement Act of 1992 (Public Law 102-282, 102nd Congress); and all other applicable federal,
state, and local laws or standards. You shall ensure that all of Your associates, colleagues and employees involved in the
conduct of the Study at Your facility or institution also understand these obligations.
You acknowledge that You have read and understand all information in the investigator's brochure provided to
You by Lilly, including the potential risks and side effects of the Study drug.
You agree not to pay fees to another physician for the referral of patients.
You agree to only use an informed consent document which has been reviewed and approved by Lilly.
You agree that Lilly, Lilly-designated representatives and domestic or foreign regulatory agencies may inspect
Your procedures, facilities and Study records (including portions of other pertinent records for all patients in
the Study) and those procedures, facilities or Study records of any contractor or agent that You use in
conducting the Study. Information obtained from such inspections may be shared with Lilly and
Lilly-designated representatives. In the event that Lilly or Lilly-designated representatives discover that there is
a lack of compliance with this Agreement, the Protocol, Good Clinical Practice Guidelines, applicable U.S.
Confidential
David Rosenberg, M.D.
August 28, 1998
2
IND regulations or other regulatory requirements, Lilly is entitled to secure compliance or discontinue
shipments of Study drug and end Your participation in the Study, pursuant to Title 21, Part 312.56 of the Code
of Federal Regulations.
B.
Study Drug Use and Record Retention Drugs furnished for the Study will be used solely under the
Protocol and may not be used for any other purposes. All Study records must be retained for whichever period of time is
greatest: fifteen (15) years after completion or termination of the Study; two (2) years after the date of marketing
application approval for the Study drug(s) indication investigated; or two (2) years after the FDA is notified by Lilly of
discontinuation of the IND.
C.
Confidentiality and Non-Use All information provided to You by Lilly or generated by You in
connection with the Study will be kept in confidence and not used for any purpose not contemplated by this
Agreement for at least ten (10) years after the termination or conclusion of the Study, unless Lilly gives You
written permission or particular information is required by laws or regulations to be disclosed to the ERB, the
patient, local regulatory agencies, or the FDA. To the extent disclosure is requested by any other person or
entity, You shall promptly notify Lilly and shall not disclose any information without Lilly's prior written
consent or until Lilly has exhausted any legal actions it may take to prevent or limit the requested disclosure.
You shall be responsible for ensuring that Your employees and agents are obligated to these same terms of
confidentiality and non-use. The terms of confidentiality and non-use set forth herein shall supersede any prior
terms of confidentiality and non-use agreed to by the parties in connection with this Study and/or the Study
Protocol. You shall not disclose any information related to this Study or the Protocol to any third party for the
purpose of making such information (or a summary) available in any publication or electronic clinical trial
databases. Consistent with this requirement, You agree to contact the Lilly Legal Department in Indianapolis if
You are requested to provide any such information for that purpose. Lilly Legal will negotiate the terms, in
Lilly's sole discretion, under which such information shall be released, if at all. In addition, You shall not
disclose the terms of this Agreement to any third party without prior review and written approval by Lilly,
except as required by law.
D. Data and Publications Data emanating from the Study shall be the sole property of Lilly and shall be
subject to the obligations of confidentiality and non-use set forth in Section C above; provided,
however, You will be free to publish and present the results of the Study subject to the following conditions:
Lilly will be furnished with a copy of any proposed publication or presentation for review and comment sixty
(60) days prior to such presentation or submission for publication. At the expiration of such sixty (60) day
period, You may proceed with the presentation or submission for publication; Provided, however, that in the
event Lilly has notified You in writing that Lilly reasonably believes that prior to such publication or
presentation it must take action to protect its intellectual property interests, such as the filing of a patent
application claiming an invention or a trademark registration application, or taking action to protect its data
package exclusivity interests, You shall either (1) delay such publication or presentation for an additional
ninety (90) days or until the foregoing action(s) have been taken, whichever shall first occur, or (2) if You are
unwilling to delay the publication, You will remove from the publication or presentation the information which
Lilly has specified it reasonably believes would jeopardize its intellectual property interests. Under certain
circumstances, a shorter review period may be granted in writing by Lilly. You will assist Lilly in obtaining
reprints of Your publication(s) resulting from the Study.
E.
Work Product All reports, brochures, handouts, documents or other work product ("Work Product") developed
or compiled by You in connection with performing services pursuant to this Agreement shall be the property of
Lilly and shall be delivered to Lilly upon request or upon termination of this Agreement. The Work Product
shall constitute a work for hire for Lilly and, therefore, Lilly shall own all copyrights arising from Your
services under this Agreement; however, Work Product shall not include any publication reviewed and
approved by Lilly in accordance with Section I (D) above. In the event any Work Product is not deemed to
constitute a work for hire for Lilly, You hereby assign all rights, title and interest that You have or may acquire
in the Work Product to Lilly. You agree to execute without further consideration all assignments or other
documents that may be necessary or helpful to establish Lilly's ownership of the
Confidential
David Rosenberg, M.D.
August 28, 1998
3
Work Product. All Work product shall be original creations for Lilly and shall not infringe any patent,
copyright or other proprietary right of a third party. If requested, any or all Work Product owned by Lilly shall
be transferred to Lilly in a form and manner to be agreed upon by You and Lilly. The information provided to
You by Lilly in order for You to carry out the services under this Agreement, including reports, brochures,
documents, handouts, ideas, concepts, etc., and the Work Product shall at all times remain solely the property
of Lilly and shall not be utilized in any manner beyond what is called for in this Agreement. Additionally, You
shall not issue, release or disclose any information concerning the services provided under this Agreement to
any person without prior review and approval by Lilly.
F.
Inventions
If during the course of the Study, You conceive or actually reduce to practice what You believe to be a new
invention or use involving the Study drug(s), You will promptly notify Lilly. The new invention or use
shall be the sole property of and shall be assigned to Lilly.
G.
Publicity
1) Solicitation of patients. Lilly and Your ERB must approve, in writing, the text of any communication
soliciting patients for the Study before placement, including, but not limited to, newspaper and radio
advertisements, direct mail pieces, Internet advertisements or communications, and newsletters. Such
communications shall not name the Study drug(s), contain therapeutic claims or mention Lilly.
2)
Press releases. Lilly must approve, in writing, press statements by You regarding the Study or
the Study drug(s) before the statements are released.
3)
In
quires from media and financial analysts. During and after the Study You may
receive inquiries from reporters or financial analysts. Lilly requests that You confer with Your designated Lilly
Research Physician or our Corporate Communications Department (317-276-3655), before responding to such inquiries.
4)
Use of Name. You will not use Lilly's name or the names of any Lilly employees in any
advertising or sales promotional material or in any publication without the prior written permission of
Lilly.
H.
Debarment Certification (Generic Drug Enforcement Act of 1992) You agree to submit to
Lilly upon completion or termination of the Study a certification that You have not been debarred by the FDA
and that You did not use, and will not use in any capacity in connection with the Study, any individual or
person debarred by the FDA under the provisions of the Generic Drug Enforcement Act of 1992.
II. LILLY SUPPORT
Lilly will provide You with Study drug(s). In addition, Lilly will provide financial support for the Study as
follows:
A. Payee
If You are an independent investigator (i.e., You do not receive remuneration from the institution in which
the Study will be performed, and payment to You under the terms of this Agreement will not violate any
policy or agreement that You have with a third party with which You are affiliated), please acknowledge
this fact by signing Your name and inserting the date below.
I am an independent investigator:
__________________________________
Signature
________________________________
Date
Confidential
David Rosenberg, M.D.
August 28, 1998
4
Unless You acknowledge that You are an independent investigator (see above), payments will be made to
Your institution. If another payee is requested, a letter must be provided from a responsible official of
Your institution which: (1) authorizes payment to a payee other than Your institution, (2) states that such
payments can be made in concert with the rules and policies of Your institution; and (3) certifies that such
payment will not violate applicable federal, state, or local laws or regulations.
Payment will be made to:
Wayne State University
Office of Research and Sponsored Programs
656 West Kirby - Room 4006
Detroit, MI 48202
38-6028429
(Taxpayer I.D. or SS Number)
B.
VA Contracts
Lilly has contracts with the United States Department of Veterans Affairs ("VA"). If VA facilities,
employees (full or part-time), or patients will NOT be utilized by You while conducting the Study, please
acknowledge this by signing in the space provided below.
_________________________________________ ____________________________
Signature
Date
If any VA facility, employees (full or part-time), or patients will be utilized by You while conducting the
Study, please provide acknowledgment from the director or other authorized official of the VA facility
involved, either by a separate written confirmation or by signature where designated on the last page of
this Agreement, that:
1)
Your conduct of the research described in this Agreement does not conflict with
any policies of the VA or Your duties to the VA;
2)
the amount and manner of payment as described in this Agreement does not conflict with
any policies of the VA; and
3) the designated payee does not conflict with any policies of the VA.
C.
Payment Schedule
The budget attached hereto as Exhibit A ("Budget") indicates that a maximum amount of $205,151.50 will
be paid to You in connection with the Study. For those amounts designated for patient services, You will
receive payment only for the actual number of visits and procedures performed in accordance with agreed
upon procedure fees outlined in the Budget; such compensation is limited to payment for the number of
patients designated in the Budget who are enrolled in the Study within a maximum of 10 months of start,
unless Lilly has given You written approval to enroll additional patients or extend the enrollment period.
To be eligible for payment, the procedures must be performed in full compliance with the Protocol and this
Agreement, and the data submitted must be complete and correct. For data to be complete and correct,
each patient must have signed an ERB-approved consent document, and all procedures designated in the
Protocol must be carried out on a "best efforts" basis; omissions must be satisfactorily explained. It is
expected that for all items required under the Protocol for which Lilly has agreed to provide compensation,
Lilly will be the sole source of compensation.
Confidential
David Rosenberg, M.D.
August 28, 1998
5
An initial advance of $20,000.00 ("Advance") will be made within thirty (30) days of receipt by Lilly of a
fully executed copy of this Agreement. Subsequent payments, if due, will be made based on the Budget and
the data received, at monthly intervals; provided, however, that (1) the Advance shall be recovered in
fifty percent (50%) increments in the form of a credit against subsequent payments until the entire Advance
is recovered; (2) other than the final payment, Lilly shall not issue any payment for a total amount less than
Five Hundred Dollars ($500.00); (3) the final payment will be made when all patients have completed the
Study and all available data and case report forms have been received and accepted by Lilly; and (4) matters
in dispute shall be payable upon mutual resolution of such dispute. In the event that the Advance credit in
any given period exceeds the amount of a payment due, the excess credit shall carry-over and be applied
against the subsequent payment, in addition to any otherwise applicable credit. In the event the amount due
in any given period is less than Five Hundred Dollars ($500.00), such amount shall carry over without
payment to the next payment period.
When Your data are reviewed by an on-site scheduled visit of a Lilly-designated representative, You will
have all reasonably available data obtained through the preceding day complete and ready for evaluation.
Lilly reserves the right to refuse payment for data not received by Lilly within ten (10) days after the
representative's review.
In addition, if Lilly requests Your attendance at a Study startup meeting or other meeting necessary to
provide You information regarding the Study or Study Drug, Lilly shall reimburse You for reasonable and
necessary travel and lodging expenses that You incur to attend such meeting(s) and that have been
specifically approved in advance by Lilly. Lilly shall make such reimbursements within thirty (30) days of
receiving acceptable detailed documentation of such expenses, provided that Lilly receives such
documentation within sixty (60) days of the date that the expenses were incurred.
D.
Subject Injury Reimbursement Lilly agrees to reimburse You for the following additional costs:
(1)
All reasonable and customary costs incurred by You and associated with the diagnosis of
an adverse event involving the Study drug or a Protocol procedure; and
(2)
All reasonable and customary costs incurred for treatment of physical injury to the subject
if Lilly determines after consulting with You that the adverse event was reasonably related to administration of the
Study drug or Protocol;
provided, however, that:
(a)
such costs are not covered by the subject's medical or hospital insurance or other governmental
program providing such coverage;
(b)
the adverse event is not attributable to Your or any agents' or employees' negligence or
misconduct;
(c)
the adverse event is not attributable to any underlying illness, whether previously
diagnosed or not; and
(d) the Study drug or Protocol procedure was administered in accordance with the Protocol.
Lilly shall have the option of paying the additional costs directly to the provider of the service or to You.
E.
Limit of Patient Entry or Enrollment and Study Termination Lilly reserves the right to limit
entry or enrollment of additional patients at any time. This may occur in a competitive-enrollment Study because
sufficient patients have been entered by other investigators to complete the needs of the Study. Lilly also reserves the
right to terminate Your or any patient's participation in the Study or the Study itself at any time for any reason. In the
event Your participation in the Study or the Study itself is terminated, You agree to return, retain, or dispose of all
Study drug(s) in accordance with instructions to be provided by Lilly and regulatory requirements.
Confidential
David Rosenberg, M.D.
August 28, 1998
6
In the event of termination, payments will be made for all work that has been performed up to the date of
termination and shall be limited to reasonable non-cancelable costs which were incurred by You in
connection with the Study as required under the Protocol and contemplated in the Budget. If the Advance or
other payments exceed the amount owed for work performed under the Protocol, You agree to return the
excess balance to Lilly.
III. INDEMNIFICATION
In consideration of the performance by You and Your staff, of ricers, agents and employees ("Indemnities") of
the work described in the Protocol and submission to Lilly of a complete report of the results of the investigation,
Lilly agrees to indemnify, defend and hold harmless the Indemnities from and against loss, damage, cost and
expense of claims and suits (including reasonable attorneys' fees) resulting from an injury to a patient seeking
damages alleged to have been directly caused or contributed to by any substance or procedure administered in
accordance with the Protocol, including the cost and expense of handling such claims and defending such suits;
provided, however, (1) that Indemnities have adhered to and complied with all applicable federal, state and local
regulations (including, without limitation, obtaining informed consents and ERB approvals), the specifications of
the Protocol and all recommendations furnished by Lilly for the use and administration of any drug or device
described in the Protocol; (2) that Lilly is promptly notified of any such claim or suit; (3) that the Indemnities
cooperate fully in the investigation and defense of any such claim or suit; (4) that Lilly retains the right to defend
the lawsuit in any manner it deems appropriate, including the right to retain counsel of its choice; and (5) that
Lilly shall have the sole right to settle the claim. In addition, Lilly's obligation of indemnification shall not extend
to any loss, damage or expense arising from the negligence, willful malfeasance or malpractice by the
Indemnities, it being understood that the administration of any substance in accordance with the Protocol shall
not constitute negligence or malpractice for purposes of this Agreement.
IV. SURVIVORSHIP CLAUSE
The obligations under Section I and Section III shall survive the expiration, termination, or cancellation of this
Agreement.
V. INDEPENDENT CONTRACTOR
In conducting the Study, You will be acting as an independent contractor, and not as an agent, partner, or
employee of Lilly. You will not have any authority to make agreements with third parties that are binding on
Lilly.
This Agreement represents the entire understanding between the parties, and supersedes all other agreements, express
or implied, between the parties concerning the subject matter hereof.
Confidential
David Rosenberg, M.D.
August 28, 1998
7
If the foregoing is acceptable to You, please sign the enclosed Agreements and return one original to the Business Office m
the enclosed envelope. If You have any questions, please call the Business Office at (317) 277-7A 1 1.
Sincerely.
LILLY RESEARCH LABORATORIES,
AGREED AND ACCEPTED:
a division of Eli Lilly and Company
Investigator
__________________________________
Margaret C. Cu
Medical Associate, Business Office
Lilly USA Medical Division
_________________________________
David Rosenberg, M.D.
AGREED AND ACCEPTED
Wayne State University
(If VA affiliation, authorized VA
representative signature required below:)
APPROVED AND CONFIRMED:
__________________________________
Signature of Authorized Official
__________________________________
(Name of VA Facility)
__________________________________
(Typed or Printed Name and Title)
___________________________________
(Authorized Representatives’ Signature)
__________________________________
(Date)
___________________________________
(Title)
_________________________________
Date
___________________________________
(Date)
Confidential
David Rosenberg, M.D.
August 28, 1998
8
PROTOCOL B1Y-MC-HCJE
FLUOXETINE VS. PLACEBO IN CHILDHOOD/ADOLESCENT
DEPRESSION
FUNDING AGENCY:
LILLY RESEARCH LABORATORIES
PER PATIENT BUDGET:
INDIRECT – 18%TDC
STUDY PERIOD I-II:
20 PATIENTS
$3608.88 – Direct Costs
$ 649.50 Indirect Costs
$4258.38 / patient x 20 patients
STUDY PERIOD III – V:
14 Patients
$4797.06- Direct Costs
$ 863.47- Indirect Costs
$5660.53 / patient x 14 patients
STUDY PERIOD VI:
= $ 72,179
= $ 12,991
$ 85,170
= $ 67,158.85
= $ 12,088.65
$ 79,247.50
8 Patients
$4315.04 – Direct Costs
$ 776.71 Indirect Costs
$5091.75 / patient
x 8 patients
TOTAL COSTS FOR ALL PERIOD
= $ 34,520
= $ 6,214
$ 40,734
$205,151.50
Confidential
David Rosenberg, M.D.
August 28, 1998
9
Budget Worksheet
Name:
Tax ID#::
Signature:
Regional Research Manager:
_________________________________
_________________________________
_________________________________Date: _____
_______________________
Date: _____
Check Paid to: __________________________________
Street Address: __________________________________
City, State, Zip: __________________________________
.
Confidential
David Rosenberg, M.D.
August 28, 1998
10
.
Budget Worksheet
PROTOCOL: B1Y-MC-HCJE
_____________________________________
TITLE: Fluoxetine Versus Placebo in Childhood/Adolescent Depression
Study Period HI
Activity/Test/Procedure
History & Physical (V1)
Investigator Fee ( V1-3)
Investigator Fee (V4)
Study Coordinator Fee (V1)
Study Coordinator Fee (V2-V4)
K-SADS(Aff.Dis.only)(V2-4)
Rater A (V1-3)
Rater B (V1-3)
Rater (V4)
Laboratory Handling Fee (V1)
PK Handling (V1)
ECG (V1)
Admin./Recruit Fee V4 Enrollment
Total Activity Cost
Overhead
Miscellaneous Costs
Patient Travel/Inconvenience
Dry Ice
Cost/
Visit
$300.00
$125.00
$100.00
$125.00
$100.00
$100.00
$175.00
$175.00
$125.00
$25.00
$25.00
$125.00
$100.00
Visit
1
3
1
1
3
3
3
3
1
1
1
1
1
21%
Cost /
Visits
#Visits
25
7
Total
Cost/Activity
$300.00
$375.00
$100.00
$125.00
$300.00
$300.00
$525.00
$525.00
$125.00
$25.00
$25.00
$125.00
$100.00
$0.00
$2,950.00
$619.50
$3,569.50
Total Misc. Costs
4
1
Total Miscellaneous Costs:
# of Patients:
20
Total Patient Cost:
Total Items
Screen Failures
$1,107.00
Advertising(with receipt)
IRB(with receipt)
$100.00
$7.00
$0.00
$107.00
$73,530.00
Overhead
$221.00
# screens
5
$6,640.00
$4,000.00
$1,000.00
$11,640.00
Total Cost of Study Period I-II
$85,170.00
Budget Worksheet
Confidential
David Rosenberg, M.D.
August 28, 1998
11
PROTOCOL: B1Y-MC-HCJE
COMPOUND: Fluoxetine
TITLE: Fluoxetine Versus Placebo in Childhood/Adolescent Depression
Study Period III – V
Cost
Visit
$150.00
$100.00
$125.00
$100.00
$100.00
$125.00
$100.00
$125.00
$25.00
$25.00
$125.00
Activity/Test/Procedure
Physical (V15)
Investigator Fee (V5-V14)
Investigator Fee (V15)
K-SADS(Aff.Dis.only)(V10.15)
Study Coordinator Fee (V5-14)
Study Coordinator Fee (V15)
Rater (V5,6,7,9,12,14)
Rater (V8,10,11,13,15)
Laboratory Handling Fee (V15)
PK Handling (V7, V15)
ECG (V15)
Total Activity Costs
Overhead
Patient Travel/ Inconvenience
Dry Ice
Unscheduled Visit
Compliant patient LOE or AE
discontinuation (Per. III-V) therapy
transition. Up to 4 visits/pt.
Paid on invoice.
1
10
1
2
10
1
6
5
1
2
1
$150.00
$1,000.00
$125.00
$200.00
$1,000.00
$125.00
$600.00
$625.00
$25.00
$50.00
$125.00
$4,025.00
21%
Miscellaneous Costs
Total Miscellaneous Costs
# of Patients:
Total
Cost/Activity
#Visit
$845.25
$4,870.25
Cost/
Visit
25
7
# Visits
Total Misc. Costs
11
2
$275.00
$14.00
$0.00
$289.00
Overhead
$42.00
#Visits
4
$968.00
$26.25
40
$6,050.00
14
Total/Visit
$200.00
$125.00
Total Patient Cost
$79,247.50
Total Cost of Study Period III - V
$79,247.50
Budget Worksheet
Confidential
David Rosenberg, M.D.
August 28, 1998
12
PROTOCOL: B1Y-MC-HCJE
COMPOUND: Fluoxetine
TITLE: Fluoxetine Versus Placebo in Childhood/Adolescent Depression
Study Period VI
Activity/Test/Procedure
Physical (V26)
Investigator Fee (V16-V-25)
Investigator Fee (V26)
Study Coordinator Fee (V16-25)
Study Coordinator Fee (V26)
K-SADS (Aff. Dis.only) (V26)
Rater (V16, 18, 20, 23, 25)
Rater ( V17, 19, 21, 22 24, 26)
Laboratory Handling Fee (V26)
PK Handling (V26)
ECG (V26)
Total Activity Costs
Overhead
Miscellaneous Costs:
Patient Travel/ Inconvenience
Dry Ice
Total Miscellaneous Costs:
# of Patients:
8
Total/Visit
Unscheduled Visit
$200.00
Total Patient Cost:
Total Cost of Study Period: VI
Total Cost of Protocol
Cost/
Visit
$150.00
$100.00
$125.00
$100.00
$125.00
$100.00
$100.00
$125.00
$25.00
$25.00
$125.00
Total
Cost/Activity
$150.00
$1,000.00
$125.00
$1,000.00
$125.00
$100.00
$500.00
$750.00
$25.00
$25.00
$125.00
$3,925.00
$824.25
$4,749.25
#Visits
1
10
1
10
1
1
5
6
1
1
1
21%
Cost/
Activity
25
7
#Visits
Overhead
$42.00
#Visits
Total Misc. Costs
11
1
$275.00
$7.00
$0.00
$282.00
2
$484.00
$40,734.00
$40,734.00
$205,151.50
Confidential
David Rosenberg, M.D.
August 28, 1998
13
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David Rosenberg, M.D.
August 28, 1998
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Confidential
David Rosenberg, M.D.
August 28, 1998
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David Rosenberg, M.D.
August 28, 1998
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David Rosenberg, M.D.
August 28, 1998
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Confidential