Master Services Agreement - CancerVax Corp., the John Wayne Cancer Institute and Synteract Inc.
MASTER SERVICES AGREEMENT
THIS MASTER SERVICES AGREEMENT ("Master Agreement") is made and entered
into as of the 22 day of January, 2002 (the "Effective Date"), by and between
CancerVax Corporation ("CancerVax"), a Delaware corporation having a place of
business at 5931 Darwin Court, Carlsbad, California, 92008 and the John Wayne
Cancer Institute ("JWCI"), a California nonprofit corporation having a place of
business at 2200 Santa Monica Boulevard, Santa Monica, California, 90404, on the
one hand, and Synteract, Inc. ("Synteract"), a California corporation having a
place of business at 187 Calle Magdelena, Encinitas, California, 92024, on the
other hand, with reference to the following:
A. WHEREAS, CancerVax is the sponsor of certain Phase 3 clinical
studies of an investigational cancer vaccine for use in advanced stage melanoma
(the "Studies") under Investigational New Drug ("IND") number 6517;
B. WHEREAS, the Studies are currently funded by NIH Program
Project Grant Nos. CA12582 and CA76489 to JWCI (the "NIH Grants");
C. WHEREAS, CancerVax and JWCI shall, concurrently with the
execution of this Master Agreement, enter into an agreement (the "Letter
Agreement") which allocates between them financial responsibility for the fees
and expenses charged by Synteract in connection with the provision of the
services hereunder;
D. WHEREAS, Synteract is duly qualified to provide certain data
management and support services as described in the Work Order(s) (as such term
is defined below) attached hereto; and
E. WHEREAS, CancerVax, JWCI and Synteract desire to enter into
this Master Agreement to set forth the terms and conditions upon which Synteract
shall be engaged from time to time to provide services in relation to the
Studies by executing individual Work Orders, specifying the details of the
services and related terms and conditions;
NOW, THEREFORE, in consideration of the covenants and agreements
hereinafter set forth, the parties hereto agree as follows:
1. Scope of the Agreement; Work Orders; Nature of Services; Direction of
Services.
A. Scope of the Agreement: Under the Master Agreement, the
parties hereto may contract for multiple projects from time to time through the
issuance of multiple Work Orders (as defined below).
B. Work Orders. The specific services to be provided and related
terms and conditions of each project under the Master Agreement shall be
separately negotiated and specified in writing in a form acceptable to CancerVax
and Synteract (each such writing, a "Work Order," an example of which is
attached hereto as Exhibit A).
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C. Nature of Services. The services covered by the Master
Agreement may include data management, data transfer, programming and data
analysis, generation of clinical and statistical study reports, project
management, and data backup and security services, and other services requested
by CancerVax and agreed to by Synteract, as set forth in an approved Work Order
(collectively, the "Services").
D. Direction of Services. JWCI and CancerVax shall each designate
an individual to serve as primary liaison with respect to each Work Order, with
the CancerVax representative having the right to make all final decisions with
respect to all matters which relate to any clinical study which may ultimately
be included by CancerVax in a marketing application to the U.S. Food and Drug
Administration ("FDA") or any equivalent foreign regulatory agencies. Each Work
Order shall be signed by an officer of each of the parties hereto and shall
include, as appropriate, the Project protocol, scope of services to be provided,
time frames for provision of the services, budget and payment schedule. Each
Work Order shall be subject to all of the terms and conditions of the Master
Agreement, in addition to the specific terms and conditions set forth in the
Work Order. In the event that any terms or conditions of a Work Order conflict
with the terms and conditions of the Master Agreement, the terms and conditions
of the Master Agreement shall control, except to the extent that the applicable
Work Order expressly and specifically states an intent to supersede the Master
Agreement in relation to a specific provision.
2. Payment of Fees and Expenses. Synteract's compensation and payment for
the Services provided hereunder shall be as set forth in the applicable Work
Order (the "Fees & Expenses"). The parties hereto agree that JWCI's financial
liability to Synteract for the Fees & Expenses shall be limited to the amounts
available to JWCI under the NIH Grants, payable as set forth in the Letter
Agreement, and that the balance of any monies owed to Synteract for the Fees &
Expenses shall be paid by CancerVax. (Each of Synteract and CancerVax
acknowledges and agrees that the obligation of JWCI to make payments required
hereunder shall be limited to the amount of the NIH Grants.) Synteract shall
invoice CancerVax on a monthly basis for the Fees & Expenses it incurs in
performing the Services. CancerVax shall provide a copy of Synteract's invoices
to JWCI and, within twenty-five (25) days after receipt of such invoices, JWCI
shall send to CancerVax a check, payable to Synteract, for the portion of the
invoiced amount which is payable by JWCI in accordance with the Letter
Agreement. CancerVax shall forward JWCI's check to Synteract, along with payment
for the undisputed balance of the invoice, net thirty (30) days after
CancerVax's receipt of Synteract's invoice. . Synteract shall receive no royalty
or other remuneration on the production or distribution of any products
developed by CancerVax or by Synteract in connection with or based upon the
Services. CancerVax shall reimburse Synteract for all reasonable out-of-pocket
expenses and disbursements actually incurred which are customary and necessary
to the provision of the Services and which CancerVax has approved in advance.
Synteract shall provide evidence reasonably satisfactory to CancerVax of all
such expenses and disbursements for which reimbursement is requested.
3. Term. The term of this Master Agreement shall commence as of the
"Effective Date" and terminate on December 31, 2005, unless sooner terminated
pursuant to Section 4 below, or unless the term hereof is extended by the mutual
written agreement of the parties hereto.
4. Termination. This Master Agreement (including all outstanding Work
Orders) may be terminated:
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A. By CancerVax or Synteract, without cause, effective upon
ninety (90) days prior written notice to CancerVax or Synteract, as appropriate,
at any time during the term of the Master Agreement;
B. By CancerVax or Synteract, for material breach of the Master
Agreement or any Work Order, effective upon thirty (30) days prior written
notice to the non-breaching party; or
C. By JWCI, in the event that JWCI lacks sufficient funding to
continue to support the Studies and provided that CancerVax does not agree to
provide such funding to Synteract, effective upon thirty (30) days written
notice to CancerVax and Synteract.
D. In the event that the Master Agreement or any Work Order(s)
hereunder are terminated, Synteract shall cease performing any work not required
for the orderly close out of the affected Work Order(s), including the
fulfillment of regulatory requirements as directed by CancerVax. All
Confidential Information and CancerVax Property (as such terms are defined
below) regardless of the method of storage or retrieval, as well as all
statistical data, statistical reports, data entries and documentation produced
as a result of the Services performed by Synteract hereunder, shall be promptly
delivered to CancerVax by Synteract.
5. Change Orders. Any change to a Work Order shall be by written
amendment, signed by each of the parties hereto.
6. Confidentiality. Synteract agrees to maintain Confidential Information
in accordance with the following terms:
A. Confidential Information. "Confidential Information" shall
mean all technical information relating to Studies, including where appropriate
and without limitation, any information, patent disclosure, patent applications,
know-how, inventions, structures, models, techniques, processes, compositions,
formulae, compounds, apparatuses, strategies, and business and financial data
relating to the Studies disclosed by CancerVax or JWCI to Synteract or obtained
by Synteract through observation or examination of information, developments or
demonstrations. Confidential Information shall not include such information as
Synteract can establish by written documentation to: (1) have been publicly
known; (2) have become publicly known, without fault on the part of Synteract,
subsequent to disclosure by CancerVax or JWCI of such information to Synteract;
(3) have been otherwise known to Synteract prior to communication by CancerVax
or JWCI to Synteract of such information; or (4) have been received by Synteract
at any time from a source other than CancerVax or JWCI lawfully having
possession of such information.
B. Nondisclosure of Confidential Information. Synteract agrees to
hold in strict confidence and not to directly or indirectly cause, permit or
enable the disclosure, publication, transfer, misappropriation or revelation to
any person or entity of the Confidential Information, without the express prior
written consent of CancerVax. Synteract will impose upon its employees the same
obligations as contained herein. Synteract also agrees not to use the
Confidential Information for any purpose at any time, other than for the sole
purpose of providing the services under the terms of this Agreement. Synteract
further agrees that any disclosure of the Confidential Information will only be
such as is reasonably necessary to its evaluation and will only be to employees
of Synteract who are bound by written agreements with
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Synteract to maintain the Confidential Information in confidence. The
obligations of Synteract under this Section 5 shall continue for a period of
five (5) years from the date of termination or expiration of this Agreement.
Notwithstanding any provision herein to the contrary, in the
event that Synteract hereafter becomes obligated by mandatory applicable law,
regulatory rule or administrative order to disclose the Confidential Information
or any portion thereof, to any governmental authority or court, Synteract shall
immediately notify CancerVax thereof of each such requirement and identify the
documents so required thereby, so that CancerVax may seek an appropriate
protective order or other remedy with respect to narrowing the scope of such
requirement and/or waive compliance by Synteract with the provisions of this
Agreement. If, in the absence of such protective order or other remedy,
Synteract is nonetheless required by mandatory applicable law, regulatory rule
or administrative order to disclose any part of the Confidential Information
which is disclosed hereunder, Synteract may disclose such Confidential
Information without liability hereunder, provided that, Synteract shall furnish
only such portion of the Confidential Information which is legally required to
be disclosed.
7. CancerVax Property.
A. Definition. For the purposes of this Agreement, "CancerVax
Property" shall mean all data and information generated as a result of the
Services, all designs, discoveries, inventions, original works of authorship,
formulae, processes, compositions of matter, products, computer programs,
databases, trade secrets, procedures, improvements, developments, drawings,
notes, documents, information and materials made, conceived or developed by
Synteract alone or with others which result from the Services. "CancerVax
Property" under this Agreement shall not include computer programming methods
and statistical methods of analysis developed by Synteract under this Agreement
or lawfully obtained by Synteract from a third party.
B. Assignment of Ownership. Synteract hereby irrevocably
transfers and assigns any and all of its right, title, and interest in and to
CancerVax Property, including but not limited to all copyrights, patent rights,
trade secrets and trademarks, to CancerVax. CancerVax Property shall be the sole
property of CancerVax and CancerVax shall have the sole right to determine the
treatment of any CancerVax Property, including the right to keep them as trade
secrets, to file and execute patent applications on them, to use and disclose
them without prior patent application, to file registrations for copyright or
trademark on them in its own name, or to follow any other procedure that
CancerVax deems appropriate. Synteract agrees: (a) to disclose promptly in
writing to CancerVax all CancerVax Property; (b) to cooperate with CancerVax in
applying for, and to execute any applications and/or assignments reasonably
necessary to obtain, any patent, copyright, trademark or other statutory
protection for CancerVax Property in CancerVax's name as CancerVax deems
appropriate; and (c) to otherwise treat all CancerVax Property as "Confidential
Information," as defined above. These obligations to disclose, assist, execute
and keep confidential shall survive any expiration or termination of this
Agreement.
C. Moral Rights Waiver. "Moral Rights" means any right to claim
authorship of a work, any right to object to any distortion or other
modification of a work, and any similar right, existing under the law of any
country in the world, or under any treaty. Synteract hereby irrevocably
transfers and assigns to CancerVax any and all Moral Rights that Synteract may
have
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in any Services or CancerVax Property. Synteract also hereby forever waives and
agrees never to assert against CancerVax, its successors or licensees any and
all Moral Rights Synteract may have in any Services or CancerVax Property, even
after expiration or termination of this Agreement.
D. Employees' Confidentiality Agreement. If Synteract employs
others in the performance of the Services, Synteract shall ensure that each of
its employees, consultants and subcontractors who will have access to the
CancerVax Property or Confidential Information of CancerVax executes an
agreement, the form of which has been approved by CancerVax, acknowledging
CancerVax's exclusive ownership and control of the CancerVax Property,
obligating the employee, consultant or subcontractor to keep all Confidential
Information confidential and not to use the CancerVax Property or Confidential
Information in any way, commercially or otherwise, except in performing the
Services, and transferring to CancerVax and waiving any and all Moral Rights in
the Services and the CancerVax Property.
8. Independent Contractor. In the performance of this Agreement, it is
mutually understood and agreed that Synteract is at all times acting and
performing as an independent contractor with, and not as an employee, joint
venture, partner, agent, principal or lessee of CancerVax or JWCI, and nothing
in this Agreement shall be construed to create an employer-employee,
agent-principal, joint venture or partnership relationship between Synteract and
CancerVax or JWCI. Synteract shall have no authority to act on behalf of or to
enter into any contract, or incur any liability for or make any representations
on behalf of CancerVax or JWCI.
Synteract shall have no claim under this Agreement or otherwise against
CancerVax or JWCI for Worker's Compensation, Unemployment Compensation, sick
leave, vacation pay, group insurance arrangements, or any other employee
benefits. Synteract is solely responsible for providing, at Synteract's own
expense, all taxes, withholdings and other similar statutory obligations
including, but not limited to, disability insurance, unemployment insurance,
Social Security, FICA, FUTA, SDI and federal, state or any other employee
payroll taxes for Synteract and Synteract's employees, subcontractors and
consultants, and Synteract will defend, indemnify and hold CancerVax and JWCI
harmless from any and all claims made by any entity on account of an alleged
failure by Synteract to satisfy any such tax or withholding obligations. Neither
CancerVax nor JWCI shall withhold on behalf of Synteract hereunder, any sums for
income tax, unemployment insurance, social security or any other withholding
pursuant to any law or requirement of any government agency. Synteract shall
comply at Synteract's expense with all applicable provisions of worker's
compensation laws, unemployment compensation laws, federal Social Security laws
and all other applicable federal, state, and local laws, regulations and codes
relating to terms and conditions of employment required to be fulfilled by
employers or independent contractors.
9. Regulatory Compliance; Inspections. Synteract agrees that the Services
shall be conducted in compliance with all applicable laws, rules and
regulations, including but not limited to the US Food, Drug and Cosmetic Act and
the regulations promulgated pursuant thereto, and with the standard of care
customary in the contract research organization industry. Synteract hereby
certifies that it has not been debarred under the Generic Drug Enforcement Act
and that it will not knowingly employ any person or entity that has been so
debarred to perform any Services under this Agreement. CancerVax and JWCI shall
notify Synteract promptly in writing of any FDA or other governmental inspection
or inquiry concerning the Services.
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If any governmental or regulatory authority conducts, or gives notice
to Synteract of its intent to conduct, an inspection of Synteract's operations
or facilities, Synteract shall notify CancerVax prior to such inspection and use
its best efforts to ensure that a representative of CancerVax is present at all
times during such inspections. If any governmental or regulatory authority
requests that Synteract provide any data or information with respect to the
Services, Synteract shall obtain the prior written approval of CancerVax prior
to complying with such demand or request and provide CancerVax with a copy of
any such data or information prior to providing it to the governmental or
regulatory agency. During the term of the Master Agreement, Synteract shall
permit representatives of CancerVax and JWCI to examine or audit the work
performed hereunder and the facilities at which the Services are performed upon
reasonable advance notice and during normal business hours.
10. Publication. Data or information related to the Studies shall not be
published or referred to, in whole or in part, by Synteract without the prior
express written consent of CancerVax.
11. Insurance and Indemnification:
A. Each party hereto agrees to maintain, for the duration of this
Master Agreement, insurance in an amount that it reasonably believes will be
adequate to cover its obligations hereunder and, upon request, each party shall
provide to the other parties a certificate of insurance verifying that such
insurance is in effect.
B. Synteract is solely responsible for providing, at Synteract's
own expense, worker's compensation insurance for Synteract and Synteract's
employees, subcontractors and consultants, and Synteract agrees to hold harmless
and indemnify CancerVax and JWCI for any and all claims arising out of any
injury, disability or death of Synteract or any of Synteract's employees,
subcontractors and consultants except for such claims that are the result of
gross negligence or intentional misconduct of CancerVax or JWCI, its agents or
its employees. Synteract shall indemnify, defend and hold CancerVax and JWCI,
CancerVax's and JWCI's officers, directors and shareholders, free and harmless
from all claims, demands, losses, costs, expenses, obligations, liabilities,
damages, recoveries and deficiencies, including interest, penalties, attorney's
fees and costs, that CancerVax or JWCI may incur as a result of a breach by
Synteract of any representation, warranty or obligation set forth under this
Agreement. CancerVax and JWCI shall indemnify and hold harmless Synteract from
and indemnify for all claims, demands, losses, costs, expenses, obligations,
liabilities, damages, recoveries, and deficiencies, including interest,
penalties, attorneys fees and costs that Synteract may incur as the result of
gross negligence or intentional misconduct of CancerVax or JWCI, their agents
and employees.
12. No Conflict with Existing Agreements: CancerVax and JWCI hereby
acknowledge that they do not desire to acquire from Synteract any secret or
confidential know-how or information which Synteract may have acquired from
others. Synteract represents and warrants that Synteract is free to divulge to
CancerVax and JWCI, without any obligation to, or violation of, any right of
others, any and all information, practice or techniques which Synteract will
describe, demonstrate, divulge or in any other manner make known to CancerVax or
JWCI during Synteract's performance of the Services hereunder. Synteract shall
exonerate, indemnify and hold harmless CancerVax and JWCI from and against any
and all liability, loss, cost, expense,
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damage, claims or demands for actual or alleged violation of the rights of
others in any trade secret, know-how or confidential information by reason of
CancerVax's or JWCI's receipt or use of the Services or information described
above, or otherwise in connection therewith. During the term of this Agreement,
Synteract may contract for work with competitors of CancerVax or JWCI or other
groups, and Synteract may be assigned to other projects for other customers of
Synteract, however, Synteract affirms that it is not presently a party to nor
shall it enter into any agreement, which would restrict its ability to fulfill
its obligations under this Agreement.
13. Dispute Resolution: The parties will attempt in good faith to resolve
through negotiation any dispute, claim or controversy arising out of or relating
to this Agreement. Any party may initiate negotiations by providing written
notice in letter form to the other parties, setting forth the subject of the
dispute and the relief requested. Each of the recipients of such notice will
respond in writing within five days with a statement of its position on and
recommended solution to the dispute. If the dispute is not resolved by this
exchange of correspondence, then representatives of each party with full
settlement authority will meet at a mutually agreeable time and place within ten
days of the date of the initial notice in order to exchange relevant information
and perspectives, and to attempt to resolve the dispute. If the dispute is not
resolved by these negotiations, the matter will be submitted to JAMS, or its
successor, for arbitration.
The parties agree that any and all disputes, claims or controversies
arising out of or relating to this Agreement that are not resolved by their
mutual agreement shall be submitted to final and binding arbitration before
JAMS, or its successor, pursuant to the United States Arbitration Act, 9 U.S.C.
Sec. 1 et seq. Any party may commence the arbitration process called for in this
Agreement by filing a written demand for arbitration with JAMS, with a copy to
the other parties. The arbitration will be conducted in accordance with the
provisions of JAMS' Streamlined Arbitration Rules and Procedures in effect at
the time of filing of the demand for arbitration. The parties will cooperate
with JAMS and with one another in selecting an arbitrator from JAMS' panel of
neutral arbitrators, and in scheduling the arbitration proceedings. The parties
covenant that they will participate in the arbitration in good faith, and that
they will share equally in its costs. The provisions of this paragraph may be
enforced by any Court of competent jurisdiction, and the party seeking
enforcement shall be entitled to an award of all costs, fees and expenses,
including attorney's fees, to be paid by the party against whom enforcement is
ordered.
14. Employment. During the term of this Agreement and for six (6) months
after the termination of this Agreement, JWCI and CancerVax agree that they will
not hire, offer employment to, or otherwise employ or retain as an independent
contractor any employees of Synteract without the prior written consent of
Synteract, and Synteract agrees that it will not hire, offer employment to, or
otherwise employ or retain as an independent contractor any employees of JWCI or
CancerVax without the prior written consent of JWCI or CancerVax, as the case
may be.
15. Miscellaneous:
A. Waiver and Modification: This Agreement sets forth the entire
understanding of the parties with respect to the subject matter hereof and
supersedes all prior and contemporaneous agreements and understandings between
them concerning such subject matter. No waiver or modification of any provision
hereof may be made unless by a written instrument
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duly executed by each party. Any waiver or breach of any term or condition shall
not be deemed to be a waiver of any preceding or succeeding breach of the same
or any other term or condition. The failure of any party to insist upon strict
performance of any term or condition hereunder shall not constitute a waiver of
such party's right to demand strict compliance therewith in the future.
B. Assignment: Neither JWCI nor Synteract may not assign this
Agreement, or any rights, duties or obligations contained herein, to any other
person, firm, corporation or other business entity without the prior written
consent of CancerVax and any such assignment or purported assignment shall be
null and void and of no force or effect. CancerVax shall have the right to
assign this Agreement at any time without the consent of Synteract.
C. Agreement Controlling: If any provision of any exhibit to this
Agreement is in conflict or inconsistent with any provision of this Agreement,
the provisions of this Agreement shall be controlling.
D. Notices: All notices and other communications required or
permitted under this Agreement shall be in writing, served personally on,
delivered by recognized overnight courier or mailed by certified or registered
United States mail to, the party to be charged with receipt thereof at the
address specified below. Notices and other communications served by mail shall
be deemed given hereunder 72 hours after deposit of such notice or communication
in the United States Post Office as certified or registered mail with postage
prepaid and duly addressed to whom such notice or communication is to be given.
All other notices shall be deemed given hereunder upon actual receipt:
CANCERVAX:
CancerVax Corporation
5931 Darwin Court
Carlsbad, CA 92008-7302
Attn.: General Counsel
JWCI:
The John Wayne Cancer Institute
2200 Santa Monica Blvd.
Santa Monica, CA 90404
Attn: Gary Grubbs
SYNTERACT:
Synteract, Inc.
187 Calle Magdalena
Encinitas, CA 92024
Attn.: Ellen Morgan
Any such party may change said party's address for purposes of this
Section by giving to the parties intended to be bound thereby, in the manner
provided herein, a written notice of such change.
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E. Severability: All Sections, clauses thereof and covenants
contained in this Agreement are severable, and in the event any of them shall be
held to be invalid by any court, this Agreement shall be interpreted as if such
invalid Sections, clauses or covenants were not contained herein.
F. Applicable Law: This Agreement is made and shall be governed
by and construed in accordance with the laws of the State of California, without
regard to principles of conflicts of law.
G. Attorneys' Fees. If any action at law or in equity is
necessary to enforce the terms of this Agreement, the substantially prevailing
party will be entitled to reasonable attorneys' fees, costs and expenses in
addition to any other relief to which such prevailing party may be entitled.
H. Counterparts: This Agreement may be executed in one or more
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same Agreement.
I. Representation: Each party hereto hereby acknowledges that it
has been encouraged to consult with legal counsel (at such party's own expense)
prior to executing this Agreement.
[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK.]
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IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
duly executed as of the date herein above set forth.
ACCEPTED AND AGREED TO FOR:
Synteract, Inc.
"Synteract"
/s/ Ellen Morgan
By: Ellen Morgan, President
Date: 1/22/02
CancerVax Corporation
"CancerVax
/s/ David F. Hale
By: David F. Hale, President & CEO
Date: ______________________________
The John Wayne Cancer Institute
"JWCI"
/s/ Gary C. Grubbs
By: Gary C. Grubbs, EVP - Finance & Administration
Date: January 22, 2002
[SIGNATURE PAGE TO MASTER AGREEMENT]
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EXHIBIT A
SAMPLE WORK ORDER
This Work Order ("Work Order") is entered into by and between CancerVax
Corporation ("CancerVax") and the John Wayne Cancer Institute ("JWCI"), on the
one hand, and Synteract, Inc. ("Synteract"), on the other hand, with reference
to the following:
WHEREAS, the parties hereto have entered into a Master Services
Agreement dated as of November __, 2001 (the "Master Agreement"); and
WHEREAS, pursuant to the Master Agreement, Synteract has agreed to
perform certain services in accordance with written work orders entered into
from time to time describing such services.
NOW, THEREFORE, in consideration of the covenants and agreements
hereinafter set forth, the parties hereto agree as follows:
1. Work Order. This document constitutes a "Work Order" under the
Master Agreement and this Work Order and the Services contemplated herein are
subject in all respects to the terms and provisions of the Master Agreement.
2. Scope of Work.
3. Time Line.
4. Budget / Fees and Expenses
5. Payment Terms and Schedule.
IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
duly executed as of the date herein above set forth.
ACCEPTED AND AGREED TO FOR:
Synteract, Inc.
"Synteract"
____________________________________
By: Ellen Morgan, President
Date: ______________________________
CancerVax Corporation
"CancerVax"
____________________________________
By: David F. Hale, President & CEO
Date: ______________________________
The John Wayne Cancer Institute
"JWCI"
____________________________________
By: ________________________________
Date: ______________________________
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WORK ORDER NO. 1
DATA MANAGEMENT, DATA ANALYSIS AND REPORT WRITING FOR
PROTOCOL JWCI-MC-3-001A AND JWCI-MC-4-001 (THE "STUDIES")
This Work Order No. 1 ("Work Order") is entered into by and between
CancerVax Corporation ("CancerVax") and the John Wayne Cancer Institute
("JWCI"), on the one hand, and Synteract, Inc. ("Synteract"), on the other hand,
with reference to the following:
WHEREAS, the parties hereto have entered into a Master Services
Agreement dated as of December __, 2001 (the "Master Agreement"); and
WHEREAS, pursuant to the Master Agreement, Synteract has agreed to
perform certain services in accordance with written work orders entered into
from time to time describing such services.
NOW, THEREFORE, in consideration of the covenants and agreements
hereinafter set forth, the parties hereto agree as follows:
1. Work Order. This document constitutes a "Work Order" under the
Master Agreement and this Work Order and the Services contemplated herein are
subject in all respects to the terms and provisions of the Master Agreement.
2. Direction of Services. JWCI and CancerVax shall each designate
an individual to serve as primary liaison with respect to this Work Order, with
the CancerVax representative having the right to make all final decisions with
respect to all matters which relate to any clinical study which may ultimately
be included by CancerVax in a marketing application to the U.S. Food and Drug
Administration ("FDA") or any equivalent foreign regulatory agencies.
3. Scope of Work: Defined in Attachment 1.
4. Time Line: Defined in Attachment 2.
5. Budget / Fees and Expenses: Defined in Attachment 3.
6. Payment Terms and Schedule: Defined in Attachment 4.
[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK.]
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IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
duly executed as of the date herein above set forth.
ACCEPTED AND AGREED TO FOR:
Synteract, Inc.
"Synteract"
/s/ Ellen Morgan
By: Ellen Morgan, President
Date: 1/22/02
CancerVax Corporation
"CancerVax"
/s/ David F. Hale
By: David F. Hale, President & CEO
Date: January 22, 2002
The John Wayne Cancer Institute
"JWCI"
/s/ Gary C. Grubbs
By: Gary C. Grubbs, EVP - Finance and Administration
Date: January 22, 2002
[SIGNATURE PAGE TO WORK ORDER NO. 1]
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WORK ORDER NO. 1
ATTACHMENT 1: SCOPE OF WORK
1. Data Management
Synteract will utilize the Clinical DataFax system running on a Dell Power Edge
4300 Server for the entry of data for the Studies. Once entered, data will be
stored in a SAS database from which all reporting and data analyses can be done.
Quality control checks will be built in every step of the way to ensure complete
accuracy. An experienced data manager will be assigned by Synteract to the
project that will be responsible for all activities leading to a clean database.
A. Case Report Form Revisions
In order to process the data with DataFax, Synteract will modify the
patient identification fields and add specific barcodes to the top of
each CRF page. Additionally, CancerVax and JWCI require a significant
number of changes to the current case report forms. The CRFs were
initially designed by the current CRO using Teleform. Because Synteract
will need to design the data entry screens using Framemaker software in
order to build the database, Synteract will redesign the CRFs using
Framemaker, while keeping the formats as similar to the current formats
as possible.
B. Quality Control Plan
The Synteract data manager will develop a quality control plan for each
of the studies, incorporating input from CancerVax, addressing the
following:
- Data formats, codes and variable and dataset labels
- Database design
- Guidelines for the tracking, entry and review of CRFs
- Special handling procedures
- Edit check plan
- Critical data requiring 100% proofreading vs. the CRF
- Sampling plan for final quality control
- Any other QC issues/ICH Requirements
This quality control plan will be sent to CancerVax for review and
approval prior to implementation.
C. Database Creation
Four databases will be developed by Synteract: (1) Stage 3; (2) Stage 3
Post-recurrence; (3) Stage 4; and (4) Stage 4 Post-recurrence. The
database structures will be developed from the case report forms,
standardizing across studies to the extent possible. Edit checks will
be built in to identify potential errors at the point of data entry to
help to identify data entry errors and errors made in completion of the
CRFs at the site. Logical edit checks to
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be run post-entry on a regular basis will be programmed by as DataFax
batch checks and in SAS. All of the edit checks will be initially done
as "batch" checks to run on the transferred data, and then some would
be converted to "interactive" checks to be triggered at the point of
entry for the new data.
Database specifications will be provided to CancerVax for review and
approval.
2. Data Transfer
Procedures, programming code and validation specifications for data and
image transfer will be developed concurrently with the database
development activities. When the database creation is complete, the
databases and images will be transferred and the transfer validated.
3. Data Management
A. Data Collected with FaxCollect
Synteract will do an initial audit of the data entered into FaxCollect
after the import into DataFax. The database would be checked against
the entire CRF for 10% of the patients, randomly selected. If errors
are found resulting from the import, these will be corrected. If a data
entry error rate exceeding 0.5% is found, then this will be discussed
with CancerVax in order to make a decision on how to proceed.
All edit checks will initially be set up as "batch" edit checks, which
are run on data after entry. These batch checks will be run on all of
the data that are transferred from the FaxCollect system. Queries
resulting from these checks will be compiled into Quality Control
Reports that are faxed to the sites. Once the batch checks are run on
all of the transferred data, some of the checks will be modified to run
interactively on the new data. A flow chart outlining the process for
handling these data is included on page 18.
B. Faxing/Entry Process - New Data
Upon completion of the case report forms at the clinical site, they are
to be faxed using standard fax machines. Synteract's trained data
management personnel will review the CRFs and data records using the
DataFax Validation tool. Using this tool, the image of the CRF will
appear on the bottom half of the screen, while the database
representation of the same data will appear on the top half. Data that
can be read using optical character recognition (numeric fields, check
boxes and choice fields) will be automatically entered into the
appropriate fields. Synteract's data management personnel will perform
a "second entry", by reviewing the data to ensure that data have been
accurately recognized, making corrections as necessary, and entering
text data which cannot be recognized (such as adverse events and
comments). Using the agreed upon CRF review guidelines and the software
tools, a detailed review of each CRF will be performed by Synteract's
data management personnel, identifying conflicting, unclear or
incomplete data. Batch edit checks will be run. "Queries" and
missing/overdue visits will be identified in Quality Control Reports
that are faxed to the sites. Queries on new data will be sent to the
sites within 7 days of CRF receipt.
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When the site receives the DataFax Quality Control Reports, they are
instructed to make the corrections on the original case report form
page, initialing and dating the changes. Each page containing a change
or addition is to be re-faxed to Synteract. When received by DataFax,
the software recognizes re-faxed pages as updates of originals through
the bar code and id information at the top of the page. Data management
personnel at Synteract then review the updated pages against the
previous versions, and enter the updated data into the database.
DataFax maintains an audit trail by keeping each version of each CRF
along with the date faxed. When all data are complete and correct for a
given patient, the CRF is signed, dated and faxed by the investigator,
indicating agreement with all changes that were made prior to the date
of signature. Any changes to the CRF which must be made after the
investigator has signed are done though query forms that are signed by
the investigator.
C. Adverse Events and Medications Coding
Adverse events will be coded using MedDRA Version 4.0 and concomitant
medications will be coded using WHO Drug 2001. Appropriate codes will
be agreed with CancerVax, and coding reports (consistency and
uncodeable reports) will be generated monthly for review and approval.
D. Laboratory Normal Ranges
Normal ranges will be collected and entered for each laboratory used.
Numerous checks, including resolution of lab normal ranges collected on
original (Quintiles) CRFs, will be performed to ensure the completeness
and appropriateness of normal ranges. Checks will include comparing the
normal range units to the units of the laboratory data collected,
looking at values outside of the normal ranges, obvious mismatches
between ranges and units, etc. "Queries" will be generated as
necessary.
C. Serious Adverse Event Notification
A programmatic trigger will alert the data manager of each serious
adverse event as the data are entered, and the data manager will send
an email to the appropriate personnel at CancerVax. A similar trigger
process will be created for withdrawal from the study due to an adverse
event and deaths.
D. Immunologic Databases
Immune function data (TA90, IgG, etc.) will be received from CancerVax
in MS Access. Synteract will incorporate this data into the SAS
database, and perform QC checking on patient identification variables.
"Queries" will be generated as necessary. It is assumed that data will
be transferred to Synteract approximately quarterly.
F. Quality Control / Assurance
After all data problems have been resolved at the site and the CRF has
been signed by the investigator, original CRFs will be transmitted to
Synteract for final quality control, while
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sites maintain a CRF photocopy. Critical efficacy and safety data will
then be verified by Synteract 100% against the final CRFs. A final
audit will then be performed by Synteract by checking the database vs.
the entire CRF for 10% of the patients, randomly selected. If errors
exceed 0.5%, then further checking will be performed. CancerVax will be
provided with a written summary of audit findings.
G. Online Access to CRFs/Other Information
Synteract will provide secure, web-based access via browser-enabled
computers to CRF images and QC notes during the study. Security will be
established using MS Proxy Server and Secure Socket Layer software to
fully protect all project information, and valid username and password
authentication will also be implemented as a standard for this project.
A log of user interaction with the project databases will be maintained
for audit and tracking purposes. Synteract will provide view-only
access to CRF images and database status within DataFax. Synteract will
need to charge a nominal per-user license fee to cover DataFax and
other ancillary software licenses for this service, in the event that
CancerVax or JWCI require more than two users. Such per-user license
fees shall be charged at Synteract's cost.
4. Programming and Data Analysis
Programming and statistical analysis will be done using SAS software.
Synteract has been recognized by the SAS Institute as a SAS Quality
Partner. As with data management, quality control checks will be built
into the programming and data analysis process to ensure the accurate
reporting of data.
A. Analysis Plan
It is assumed that the analysis plans already developed will be used.
B. Master Derived Datasets
Derived datasets have been developed by the current CRO. If the
programming code can be obtained, a Synteract statistician will review,
validate and correct the programs as needed. Additional derived
datasets may be prepared by Synteract for data such as study treatment,
adverse events and laboratory data.
C. Programming/Validation
After approval of the analysis plan by CancerVax, Synteract programmers
will develop the programs to generate the tables and listings using SAS
according to the agreed analysis plan.
The programmer will be responsible for the accuracy of his/her own
work, but all outputs will be independently verified for accuracy and
consistency by a second individual. This validation will be carried out
by a combination of independent programming, cross-checking, and
verification against CRFs. A quality assurance binder will be prepared
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which contains a sample of each output, the SAS program used to produce
it, and the quality assurance checks performed.
Tables and listings will be provided in rich text format for
incorporation into the clinical study report. Figures will be provided
in electronic format to be mutually agreed upon. Electronic copies of
all programming code will be provided to CancerVax at study completion.
All output will be generated according to CancerVax electronic
submission standards.
D. Statistical Analyses
Statistical analyses in accordance with the approved statistical
analysis plan will be performed by a biostatistician.
E. Patient Profiles
Patient profiles will be developed which integrate all data for each
patient into a single report. There will be no charge for these if
Synteract's standard format is used. Specific formats that require
additional programming may require an additional charge.
F. Interim Analyses
Synteract will generate and perform quality control of the required
tables, listings and analyses for each interim review. Data will be
provided to the appropriate party for review. Up to 3 interim analyses
will be done for each of the two Studies.
5. Data Transfers
Transfer of SAS(R) Transport Files will occur as requested by
CancerVax. Transfer of ASCII data of select information including, but
not limited to, number of queries generated, queries outstanding,
visits outstanding, etc, will occur biweekly in order to populate the
CancerVax / JWCI Clinical Information System (CIS).
At project completion, Synteract will provide the following items to
CancerVax in appropriate electronic form:
- Final SAS datasets, including both raw and analysis
datasets;
- Full description of the database content and all related
documentation;
- Adverse event coding mapping dataset; and
- Case report form images in PDF format according to FDA
guidelines ready for submission.
6. Integrated Clinical/Statistical Study Report
The statistical report will be designed to be used in conjunction with
a description of the medical aspects of the trial to produce the
Integrated Clinical/Statistical Report, which is a complete report of
the trial. The Synteract clinical writer will work with CancerVax to
develop a report format that satisfies both content and stylistic
preference and FDA and ICH Guidelines.
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A draft clinical report will be generated within 3-5 weeks after
database closure.
The draft report includes final tables, listings and statistical
evaluation. The cost of this report includes one major and one minor
revision of the report. Narratives of serious adverse events, deaths
or discontinuations due to adverse events can be done, but are not
included in the cost estimates. The draft report will be circulated by
Synteract for review by CancerVax ; comments/changes will be collated,
and the Report will be revised by Synteract accordingly for final
approval by CancerVax. Prior to finalization, an independent quality
assurance review of the Report will be performed by Synteract.
7. Project Management
A. Project Management Plan
Synteract will develop a Project Management Plan that will describe
Synteract's roles and responsibilities in relation to those of
CancerVax and JWCI. The project plan will include methods and modes of
communication, milestones and key staff representatives as functional
points of contact. The Project Plan will also present the specifics and
timing (e.g. weekly, monthly or quarterly) of the reports to be
provided to CancerVax. CancerVax may provide input to the project plan
before approving it.
Synteract will provide status reports on a bi-weekly basis summarizing
CRFs received and processed, queries generated, queries outstanding,
visits outstanding, patients randomized, etc. Status data can be
provided in Excel or ASCII format. The content and format of the metric
reports will be finalized in conjunction with CancerVax.
B. Communication, Project Meetings and Timeline Management
Synteract manages all projects according to a Project Team approach.
The Synteract Project Manager will have the primary responsibility of
communication with CancerVax and JWCI for overall project information
for the duration of the project, however, CancerVax and JWCI are
welcome to contact any team members as needed. This includes daily,
weekly and monthly updates to keep core team members current on all
project activities.
An initial project planning meeting will take place between CancerVax
and Synteract project team members. Synteract will host a subsequent
meeting to train the CancerVax Clinical Research Associates (CRAs) on
the specific procedures of the DataFAX system.
Synteract will plan for weekly meetings with CancerVax that will
include the Project Manager, Data Manager and other key functional area
personnel, as required. These meetings will be either via
teleconference, or in person.
During each meeting, critical issues, unexpected problems and trends
will be identified and discussed. In addition, milestones will be set
and reviewed and timelines for all departments working on the project
are discussed. Any deviations in project deadlines, expenses and action
items will be examined with respect to the impact on all
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departments. Additionally, the team members will "trouble-shoot"
problems and solutions before milestones or deadlines are jeopardized.
Meeting minutes will be distributed to all team members.
All key events and tasks will be tracked and updated utilizing MS
Project, with updates provided to the Project Team on a regular basis.
8. Backup and Security
As part of standard procedure, all files and programs will be fully
backed up by Synteract nightly. Full backups performed by Synteract and
will be sent weekly to secure off-site storage for disaster recovery.
Databases are password protected, and only Synteract authorized
personnel will have access.
For website security, Synteract will implement:
- VeriSign(TM) Secure Server ID
- Secure Socket Layer (SSL) 3.0
- User authentication
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WORK ORDER NO. 1
ATTACHMENT 2: TIME LINE
<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------------
TARGET DATE/
ACTIVITY STUDY RESPONSIBLE COMPLETION DATE
--------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
Project initiation [***]
Complete feasibility assessment [***]
Draft CRF (Unique Pages) Stage 3 Syn [***]
CRF Comments Stage 3 CV [***]
Full CRF book Stage 3 Syn [***]
Draft Edit Checks Stage 3 Syn [***]
Final CRF Stage 3 Syn/CV [***]
Draft CRF Recurrence & Stage 4 Syn [***]
CRF Comments Recurrence CV [***]
Edit Check Comments Stage 3 CV [***]
CRF Comments Stage 4 CV [***]
Final CRF Recurrence Syn/CV [***]
Final Edit Checks Stage 3 Syn/CV [***]
Final CRF Stage 4 Syn/CV [***]
Draft Edit Checks Recurrence Syn [***]
Edit Check Comments Recurrence CV [***]
Draft Edit Checks Stage 4 Syn [***]
Final Edit Checks Recurrence Syn/CV [***]
Edit Check Comments Stage 4 CV [***]
Final Edit Checks Stage 4 Syn/CV [***]
Complete database set-up Stage 3 Syn [***]
Transfer of Fax Collect Datasets & Images All CV [***]
Complete Database set-up Stage 4 Syn [***]
Complete Database set-up Recurrence Syn [***]
Begin receiving faxes All Syn [***]
Begin QC of Fax Collect Data All Syn [***]
Complete data transfer/validation All Syn [***]
</TABLE>
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
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<PAGE>
<TABLE>
<CAPTION>
--------------------------------------------------------------------------------------------------------------
TARGET DATE/
ACTIVITY STUDY RESPONSIBLE COMPLETION DATE
--------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
RANDOMIZATION PROCESS
Draft CRFs Random Syn [***]
CRF Comments Random CV [***]
Final CRF Random Syn/CV [***]
Receipt of Randomization Schedule Random CV [***]
New Manufacturing Shipping Process Random CV [***]
Database and Programming Complete Random Syn [***]
MOCK REPORT METHODOLOGY
Draft Report Shell Stage 3 Syn [***]
Report Shell Comments Stage 3 CV [***]
Revised mock report [***]
Stage 4 [***]
TABLE PROGRAMMING
Begin Programming on Stage 3 [***]
Tables for interim analysis [***]
Remaining Efficacy Tables [***]
Remaining Safety Tables [***]
</TABLE>
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
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WORK ORDER NO. 1
ATTACHMENT 3: BUDGET / FEES & EXPENSES
1. Assumptions
The following assumptions have been made in determining the cost
estimates for each of the two Studies:
STAGE 3 MELANOMA (JWCI-MC-3-001A)
<TABLE>
<CAPTION>
---------------------------------------------------------------------------------------------------------
RECEIVED BY
FAXCOLLECT NEW CRF
---------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
Number of Existing Patients [***]
---------------------------------------------------------------------------------------------------------
Average Number of CRFs per Patient [***] [***]
---------------------------------------------------------------------------------------------------------
Estimated CRF volume (pages) [***] [***] [***]
---------------------------------------------------------------------------------------------------------
Number of New Patients [***]
---------------------------------------------------------------------------------------------------------
Estimated CRF volume (pages) [***]
---------------------------------------------------------------------------------------------------------
Estimated Total CRF volume [***] [***]
---------------------------------------------------------------------------------------------------------
---------------------------------------------------------------------------------------------------------
Number of edit checks [***]
---------------------------------------------------------------------------------------------------------
Number of queries per patient [***]
---------------------------------------------------------------------------------------------------------
Number of laboratories [***]
---------------------------------------------------------------------------------------------------------
Number of analysis datasets [***]
---------------------------------------------------------------------------------------------------------
Number of tables for primary analysis [***]
---------------------------------------------------------------------------------------------------------
Number of data listings [***]
---------------------------------------------------------------------------------------------------------
Number of graphs [***]
---------------------------------------------------------------------------------------------------------
Number of interim analyses [***]
---------------------------------------------------------------------------------------------------------
Number of tables for each interim [***]
analysis
---------------------------------------------------------------------------------------------------------
</TABLE>
STAGE 3 POST-RECURRENCE
<TABLE>
<CAPTION>
---------------------------------------------------------------------------------------------------------
RECEIVED BY
FAXCOLLECT NEW CRF
---------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
Number of Existing Patients [***]
---------------------------------------------------------------------------------------------------------
Average Number of CRFs per Patient [***] [***]
---------------------------------------------------------------------------------------------------------
Estimated CRF volume (pages) [***] [***] [***]
---------------------------------------------------------------------------------------------------------
Number of New Patients [***]
---------------------------------------------------------------------------------------------------------
Estimated CRF volume (pages) [***]
---------------------------------------------------------------------------------------------------------
Estimated Total CRF Volume [***] [***]
---------------------------------------------------------------------------------------------------------
---------------------------------------------------------------------------------------------------------
Number of edit checks [***]
---------------------------------------------------------------------------------------------------------
Number of queries per patient [***]
---------------------------------------------------------------------------------------------------------
TOTAL CRF PAGES: [***] [***]
</TABLE>
* If entire CRF for a given patient used the existing CRF
** Revised CRF will have approximately 20% fewer pages than existing CRF.
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
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STAGE 4 MELANOMA (JWCI-MC-4-001)
<TABLE>
<CAPTION>
---------------------------------------------------------------------------------------------------------
RECEIVED BY
FAXCOLLECT NEW CRF
---------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
Number of Existing Patients [***]
---------------------------------------------------------------------------------------------------------
Average Number of CRFs per Patient [***] [***]
---------------------------------------------------------------------------------------------------------
Estimated CRF volume (pages) [***] [***] [***]
---------------------------------------------------------------------------------------------------------
Number of New Patients [***]
---------------------------------------------------------------------------------------------------------
Estimated CRF volume (pages) [***]
---------------------------------------------------------------------------------------------------------
Estimated Total CRF volume [***] [***]
[***]
---------------------------------------------------------------------------------------------------------
---------------------------------------------------------------------------------------------------------
Number of edit checks [***]
---------------------------------------------------------------------------------------------------------
Number of queries per patient [***]
---------------------------------------------------------------------------------------------------------
Number of laboratories [***]
---------------------------------------------------------------------------------------------------------
Number of analysis datasets [***]
---------------------------------------------------------------------------------------------------------
Number of tables for primary analysis [***]
---------------------------------------------------------------------------------------------------------
Number of data listings [***]
---------------------------------------------------------------------------------------------------------
Number of graphs [***]
---------------------------------------------------------------------------------------------------------
Number of interim analyses [***]
---------------------------------------------------------------------------------------------------------
Number of tables for each interim analysis [***]
---------------------------------------------------------------------------------------------------------
</TABLE>
STAGE 4 POST-RECURRENCE
<TABLE>
<CAPTION>
---------------------------------------------------------------------------------------------------------
RECEIVED BY
FAXCOLLECT NEW CRF
---------------------------------------------------------------------------------------------------------
<S> <C> <C> <C>
Number of Existing Patients [***]
---------------------------------------------------------------------------------------------------------
Average Number of CRFs per Patient [***] [***]
---------------------------------------------------------------------------------------------------------
Estimated CRF volume (pages) [***] [***] [***]
---------------------------------------------------------------------------------------------------------
Number of New Patients [***]
---------------------------------------------------------------------------------------------------------
Estimated CRF volume (pages) [***]
---------------------------------------------------------------------------------------------------------
Estimated Total CRF Volume [***] [***]
[***]
---------------------------------------------------------------------------------------------------------
---------------------------------------------------------------------------------------------------------
Number of edit checks [***]
---------------------------------------------------------------------------------------------------------
Number of queries per patient [***]
---------------------------------------------------------------------------------------------------------
TOTAL CRF PAGES: [***] [***]
[***]
</TABLE>
* If entire CRF for a given patient used the existing CRF
** Revised CRF will have approximately 20% fewer pages than existing CRF.
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
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Other Assumptions
- CancerVax will have responsibility for clinical monitoring
activities.
- Cost estimates for data collected with FaxCollect assume that
images can be electronically routed to the correct patient id.
- It is assumed that immunologic data will be transferred to
Synteract in Access approximately quarterly for incorporation
into the SAS database.
- It is assumed that pre-recurrence data will be entered into a
database separate from the post-recurrence data, but that the
data will be analyzed as one.
- Programming cost estimates assume that Synteract standard
patient profiles will be adequate. Additional programming effort
would be required for custom profiles.
- There will be up to 3 interim analyses for each of the two
Studies. Approximately 15-20 tables, which are a subset of the
final, planned analysis, are planned.
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Cost Estimates
STAGE 3
<TABLE>
<CAPTION>
FAXCOLLECT DATA NEW DATA
ACTIVITY RATE UNIT EST. REQ. ESTIMATED CHARGE EST. REQ. ESTIMATED CHARGE
range (1) range (1) range (1) range (1)
<S> <C> <C> <C> <C> <C> <C> <C> <C> <C> <C>
DATABASE SETUP
CRF Revision / Barcoding [***] [***] [***] [***] [***] [***]
Database Creation / Testing [***] [***] [***] [***] [***] [***]
Data Mgt Plan/Define Edit Checks [***] [***] [***] [***] [***] [***]
Data Import [***] [***] [***] [***] [***] [***]
Image Import [***] [***] [***] [***] [***] [***]
Database Setup Subtotal [***] [***]
DATA MANAGEMENT
Initial Database QC [***] [***] [***] [***] [***] [***]
Data Entry/Final QC [***] [***] [***] [***] [***] [***] [***] [***] [***] [***]
Data Management [***] [***] [***] [***] [***] [***] [***] [***] [***] [***]
Laboratory Normal Ranges [***] [***] [***] [***] [***] [***] [***] [***] [***] [***]
Data Management Subtotal [***] [***] [***] [***]
BIOSTATISTICS & MEDICAL WRITING
Analysis Datasets [***] [***] [***] [***] [***] [***]
Programming / Validation [***] [***] [***] [***] [***] [***]
Interim Analysis Tables [***] [***] [***] [***] [***] [***]
Final Statistical Analysis [***] [***] [***] [***] [***] [***]
Interim Statistical Analysis [***] [***] [***] [***] [***] [***]
Statistical Report [***] [***] [***] [***] [***] [***]
Clinical Report [***] [***] [***] [***] [***] [***]
Biostats&Medical Writing Subtotal [***] [***]
PROJECT MANAGEMENT
Project Management [***] [***] [***] [***] [***]
STUDY SUBTOTAL [***] [***] [***] [***]
OVERALL TOTAL [***] [***]
</TABLE>
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
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Costs are based upon the study enrolling until completion, and are given as a
range to allow for flexibility. CancerVax and JWCI will only be charged for
actual time spent. Synteract shall notify CancerVax in writing immediately at
such time as Synteract anticipates that the minimum of the range will be
exceeded and shall obtain the prior written authorization of an officer of
CancerVax prior to exceeding such minimum. The maximum of the range will not be
exceeded.
STAGE 4
<TABLE>
<CAPTION>
FAXCOLLECT DATA NEW DATA
ACTIVITY RATE UNIT EST. REQ. ESTIMATED CHARGE EST. REQ. ESTIMATED CHARGE
range (1) range (1) range (1) range (1)
<S> <C> <C> <C> <C> <C> <C> <C> <C> <C> <C>
DATABASE SETUP
CRF Revision / Barcoding [***] [***] [***] [***] [***] [***]
Database Creation / Testing [***] [***] [***] [***] [***] [***]
Data Mgt Plan/Define Edit Checks [***] [***] [***] [***] [***] [***]
Data Import [***] [***] [***] [***] [***] [***]
Image Import [***] [***] [***] [***] [***] [***]
Database Setup Subtotal [***] [***]
DATA MANAGEMENT
Initial Data QC [***] [***] [***] [***] [***] [***]
Data Entry/Final QC [***] [***] [***] [***] [***] [***] [***] [***] [***] [***]
Data Management [***] [***] [***] [***] [***] [***] [***] [***] [***] [***]
Laboratory Normal Ranges [***] [***] [***] [***] [***] [***] [***] [***] [***] [***]
Data Management Subtotal [***] [***] [***] [***]
BIOSTATISTICS & MEDICAL WRITING
Analysis Datasets [***] [***] [***] [***] [***] [***]
Programming / Validation [***] [***] [***] [***] [***] [***]
Interim Analysis Tables [***] [***] [***] [***] [***] [***]
Final Statistical Analysis [***] [***] [***] [***] [***] [***]
Interim Statistical Analysis [***] [***] [***] [***] [***] [***]
Statistical Report [***] [***] [***] [***] [***] [***]
Clinical Report [***] [***] [***] [***] [***] [***]
Biostats&Medical Writing Subtotal [***] [***]
</TABLE>
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
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<TABLE>
<S> <C> <C> <C> <C> <C> <C> <C> <C> <C> <C>
PROJECT MANAGEMENT
Project Management [***] [***] [***] [***] [***]
STUDY SUBTOTAL [***] [***] [***] [***]
OVERALL TOTAL [***] [***]
</TABLE>
Costs are based upon the study enrolling until completion, and are given as a
range to allow for flexibility. CancerVax and JWCI will only be charged for
actual time spent. Synteract shall notify CancerVax in writing immediately at
such time as Synteract anticipates that the minimum of the range will be
exceeded and shall obtain the prior written authorization of an officer of
CancerVax prior to exceeding such minimum.
The maximum of the range will not be exceeded.
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
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WORK ORDER NO. 1
ATTACHMENT 4: PAYMENT TERMS AND SCHEDULE
1. Pass-Through Costs
Mailing, teleconference and travel costs are considered direct costs
and are not included in the above cost estimate. These costs will be
invoiced to CancerVax directly, without any markup.
2. Over Scope
If Synteract and CancerVax agree that it is likely that the scope of
the work to be performed by Synteract at the request of CancerVax will
exceed the scope of work contemplated in Schedule 1 to this Work Order,
then the parties hereto may agree to amend the Work Order in order to
reflect Synteract's anticipated costs associated with the expanded
scope of work, at the daily rates outlined above, not to exceed [***]
over the original estimate provided herein. The nature, time, and cost
of work over scope will be documented and the increased costs will not
be effective until such amendment is approved by of an officer of each
of the parties hereto.
Due to the duration of the Studies, Synteract reserves the right to
review the daily rates not more than once per twelve-month period to
ascertain if an increase is merited. Synteract would provide CancerVax
with written notification of any increase in rates at least ninety (90)
days prior to the effective date. Any such rate increases will not
exceed [***] per twelve-month period and will not be effective until
approved by an officer of each of the parties hereto in a written
amendment to the Work Order.
3. Payment Schedule
A payment of [***] is due within ten (10) working days following the
execution of this Work Order and will be retained by Synteract as a
deposit for the duration of the Work Order. (This is equal to the
estimated average amount of work to be done in a two-month period,
which is the average lag time in receiving payment for work actually
performed.) CancerVax will then be invoiced monthly, with a copy
provided by CancerVax to JWCI, for actual work performed. At the
completion of the project if payments received by Synteract exceed the
cost of the work completed, Synteract will promptly reimburse
CancerVax, as appropriate, for the amount overpaid.
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
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