CLINICAL RESEARCH SERVICES AGREEMENT BETWEEN YM BIOSCIENCES, INC. AND PHARM- OLAM INTERNATIONAL LTD. YB1002-203Taxotere
CONFIDENTIAL
BETWEEN
YM
BIOSCIENCES, INC.
AND
PHARM-OLAM
INTERNATIONAL LTD.
YB1002-203Taxotere
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22 February, 2005
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CONFIDENTIAL
TABLE OF
CONTENTS
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4
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1.
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DEFINITIONS
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4
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2.
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INTERPRETATION
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7
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3
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APPOINTMENT
& RELATIONSHIP OF PARTIES
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7
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4.
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REPRESENTATIONS
& WARRANTIES
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8
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5.
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POI's
OBLIGATIONS
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8
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6.
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YM's
OBLIGATIONS
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10
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7.
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LIMITATION
OF LIABILITY
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10
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8.
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CRO
COMPENSATION
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11
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9.
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AUDIT
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11
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10.
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CLINICAL
STUDY AGREEMENT NEGOTIATION
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12
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11.
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INSURANCE
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12
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12.
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CONFIDENTIALITY
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13
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13.
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INTELLECTUAL
PROPERTY
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13
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14.
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ARBITRATION
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14
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15.
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NON-SOLICITATION
OF STAFF
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14
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16.
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TERM
& TERMINATION
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14
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17
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CONSEQUENCES
OF TERMINATION
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16
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18.
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REPETITION
OF THE STUDY
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17
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19.
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DELAYS
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17
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GENERAL
PROVISIONS
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17
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21.
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APPLICABLE
LAW
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19
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CONFIDENTIAL
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SCHEDULE
1 CONTRACT SERVICES COST SCHEDULE
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SCHEDULE
2 PAYMENT SCHEDULE
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SCHEDULE
3 INVESTIGATOR AGREEMENT TEMPLATE
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CONFIDENTIAL
AGREEMENT
This
Clinical Research Services Agreement (this Agreement) is made and entered into
effective as of 10 December 2004 (the “Effective Date”), by and between YM
BIOSCIENCES, INC. (hereafter “YM”), a Canadian corporation, with its principal
office at 5045 Orbitor Drive, Building 11, Suite 400, Mississauga, Ontario L4W
4Y4, Canada, and PHARM-OLAM INTERNATIONAL Ltd. (hereafter “POI”), a Texas
limited partnership, with its principal office at 000 X Xxx Xxxxxxx Xxxxxxx,
Xxxxx 000, Xxxxxxx, XX 00000, Xxxxxx Xxxxxx.
RECITALS
WHEREAS,
YM develops, manufactures, or sells pharmaceutical products; and
WHEREAS,
POI is a contract research organization that plans, implements, and manages
clinical trials; and
WHEREAS,
YM desires to engage POI to assist YM in planning, implementing, and managing a
clinical trial on the Investigational Product, as hereafter defined;
and
WHEREAS,
POI is willing to accept such engagement on the terms and conditions set forth
herein;
NOW,
THEREFORE, in consideration of the premises and the mutual covenants and
obligations set forth herein, and for other good and valuable consideration, the
receipt and sufficiency of which are acknowledged, the parties agree as
follows:
1.
DEFINITIONS
For
purposes of this Agreement and the Protocol, each capitalized term shall have
the meaning ascribed to it in this Agreement. Each capitalized term not defined
in this Agreement shall have the meaning ascribed to that term in the Protocol.
In the event of a discrepancy in the meaning ascribed to a term in the body of
this Agreement and the meaning ascribed to that term in the Protocol, the
definition utilized in the body of this Agreement shall control.
1.1 “Case
Report Form” or “CRF” means the record of pertinent information collected on
each subject who participates in the Study;
1.2
“Clinical Laboratory Agreement” means the Agreement between POI and the clinical
laboratory or laboratories that will provide clinical laboratory services for
the Study.
1.3
“Clinical Research Associate” or “CRA” means the person assigned by POI to
monitor one or more Study sites.
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CONFIDENTIAL
1.4
“Clinical Trial Agreement” means the agreement between POI and an Investigator
that details the respective rights and obligations of both parties in relation
to the Study;
1.5
“Clinical Trial Materials” means the Investigational Product, competitor
substances, the Protocol, the investigational drug brochure, informed consent
form, guidelines for use of the Investigational Product, and all other materials
provided by YM to conduct the Study.
1.6
“Closeout Services” means those services described in Section 17 to be performed
by POI upon termination of this Agreement, or as generally accepted as
GCP.
1.7
“Confidential Information” means any information, whether written or oral,
including all notes, studies, customer lists, forms, business or management
methods, marketing data, fee schedules, or trade secrets of any member of the
POI Group or of YM, as appropriate, disclosed or otherwise made available to one
party by the other party pursuant to this Agreement. Confidential Information
shall also include the terms and provisions of this Agreement and any
transaction or documents executed by the parties pursuant to this Agreement. In
addition, Confidential Information shall include any data, including clinical
study data, or information developed or generated in the course of performance
of this Agreement. Publication of the fact that YM and POI have entered into a
clinical research service agreement, without disclosing the terms and provisions
of this Agreement, shall not be construed as unauthorized disclosure of
Confidential Information.
Confidential
Information does not include any information that (i) is or becomes generally
available to and known by the public, other than as a result of an unauthorized
disclosure directly or indirectly by the receiving party or its affiliates,
advisors, or representatives; (ii) is or becomes available to the receiving
party on a non-confidential basis from a source other than the furnishing party
or its affiliates, advisors, or representatives, provided that such source is
not and was not bound by a confidentiality agreement with or other obligation of
secrecy to the furnishing party of which the receiving party has knowledge at
the time of such disclosure; or (iii) has already been or is hereafter
independently developed by the receiving party by persons not having access to
the Confidential Information of the furnishing party.
1.8 “Data
Safety Monitoring Board” means the group of individuals appointed to monitor
safety issues relating to the Study.
1.9 “CRO
Compensation” means the compensation to be paid by YM to POI as set out in
Schedules 1 and 2.
1.10
“Effective Date” means the effective date of this Agreement as set forth in the
initial paragraph of this Agreement.
1.11
“Food and Drug Administration” or “FDA” means the United States government
agency responsible for ensuring compliance with the Food, Drug, and Cosmetics
Act of 1938.
1.12
“Force Majeure Event” means an event beyond the reasonable control of the
relevant party including, but not limited to, acts of God, a public enemy, or a
civil or military authority; fires or other catastrophes; strikes, lockouts, or
other industrial action taken by the employees of any party or any third party;
delays in transportation; riots; or invasions, wars, or threats of
war.
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CONFIDENTIAL
1.13
“Good Clinical Practice” (GCP) means the clinical standards established by the
FDA and counterpart agencies of each country in which the Study will take place,
designed to regulate the activities of YM’s investigators, monitors, and
Institutional Review Boards involved in clinical drug testing.
1.14
“Institutional Review Board/Ethics Committee” or “IRB/EC” means the independent
group of professionals designated to ensure that the Study is safe and effective
for human participation and that the Study adheres to the regulations issued by
the FDA and any other applicable country-specific laws, regulations or
guidelines.
1.15
“Investigational New Drug Application” or “IND” means the petition filed by YM
with the FDA requesting the FDA to allow human testing on the Investigational
Product.
1.16
“Investigational Product” means the product (drug, device, or biologic)
described in the Protocol that will be evaluated in this Study.
1.17
“Investigator” means an individual who actually conducts a clinical
investigation, i.e., under whose immediate direction the Investigational Product
is administered or dispensed to, or used involving a subject, or, in the event
of an investigation conducted by a team of individuals, is the responsible
leader of that team.
1.18 “POI
Group” means the following persons and entities, as constituted at the date of
this Agreement or subsequently: (i) POI; and (ii) any person or entity that
directly, or indirectly through one or more intermediaries, controls, is
controlled by, or is under common control with POI.
1.19
“POI's Obligations” means the obligations of POI under this
Agreement.
1.20
“Project Manager” means the manager assigned by POI to be the primary contact
person between POI and YM during the Study.
1.21
“Protocol” means the plan that describes the objectives, study design, and
methodology of the Study entitled, “A
Pharmacokinetic Interaction and Safety and EfficacyPhase II, Open label Study
Evaluating Docetaxel plus Tesmilifene (YMB1002) in Patients with Metastatic
Breast Cancer Suitable for Treatment with Docetaxel”, and any approved
amendments thereto, which is herein incorporated by reference and numbered YMB
1002-203.
1.22
“Regulatory Requirements” means those laws, regulations, and professional and
ethical standards and guidelines then in effect in the countries in which the
Study is conducted that apply to the Investigational Product or clinical trials
in general.
1.23
“Related Products” means any product (drug, device, or biologic), other than the
Investigational Product, administered or utilized as part of this
Study.
1.24
“Serious Adverse Event” shall take the meaning given this term in the
Protocol.
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CONFIDENTIAL
1.25
“Services” means the services to be furnished by POI in connection with the
Study as set out in this Agreement including the schedules.
1.26
“Standard Operating Procedures” or “SOP’s” means internal procedures for the
management of a clinical trial designed to ensure that the trial is carried out
in a consistent, controlled, and effective manner.
1.27
“Study” means the clinical trial of the Investigational Product, the details of
which are set out in the Protocol.
1.28
“Study Documents” means the documents produced by POI in connection with the
Study that are necessary for the production of the final study
report.
1.29
“Term” means the duration of this Agreement as set out in Section
16.
1.30
“YM’s Obligations” means the obligations of YM under this
Agreement.
2.
INTERPRETATION
2.1 Words
of any gender used in this Agreement shall be held and construed to include any
other gender, and words in the singular number shall be held to include the
plural, and the plural to include the singular, unless the context requires
otherwise.
2.2 The
headings of the sections of this Agreement are inserted for convenience only and
in no way define, limit, or prescribe the intent of this Agreement.
2.3
Unless otherwise specified, references in this Agreement to Sections and
Schedules are to the sections of, and schedules to, this Agreement. All
Schedules are deemed to be incorporated into, and form part of, this Agreement,
and the term “Agreement” shall be construed accordingly.
2.4
Unless otherwise specified, any reference to a statute, rule, or regulation
shall be to that statute, rule, or regulation as amended from time to
time.
2.5 If
the terms of this Agreement, including the Schedules, and the Protocol should
conflict, the terms of this Agreement shall control.
3
APPOINTMENT AND RELATIONSHIP OF PARTIES
3.1 YM
hereby engages the services of POI, and POI accepts such engagement, under the
terms and conditions contained in this Agreement.
3.2
During the Term, POI shall at all times be the independent contractor of YM, and
nothing in this Agreement is intended, nor shall be construed, to create between
YM and POI the relationship of principal and agent, employer and employee,
partnership, or joint venture, and the parties shall not represent themselves
otherwise.
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CONFIDENTIAL
3.3 YM
shall be liable for its own debts, obligations, acts or omissions, including but
not limited to the payment of all required compensation, withholding, social
security and other taxes or benefits for YM’s employees. Likewise, POI shall be
liable for its own debts, obligations, acts or omissions, including but not
limited to the payment of all required compensation, withholding, social
security and other taxes or benefits for the Investigators and POI’s
employees.
3.4 If
the Internal Revenue Service or any other government authority shall, at any
time, question or challenge the independent contractor status of POI, upon
receipt by either party of notice from the Internal Revenue Service or any other
governmental authority, the receiving party shall promptly notify the other
party and afford the other party the opportunity to participate in any
discussion or negotiation with the Internal Revenue Service or other government
authority, regardless as to who initiates such discussions or
negotiations.
4.
REPRESENTATIONS AND WARRANTIES
4.1 POI
warrants to YM that (i) it has the authority to enter into this Agreement; and
(ii) all consents and approvals required for the Study, have been, or will be
obtained prior to initiation of the Study, with the exception of regulatory
approval by Health Canada and the United States Food and Drug Administration,
which will be obtained by YM.
4.2 POI
warrants and represents that it has not been and is not currently an individual,
corporation, partnership, association or entity that has been debarred by the
FDA pursuant to United States regulation 21 U.S.C. §335a (a) or (b) (“Debarred
Person”). POI further warrants and represents that no Debarred Person has
performed or rendered, or will perform or render, any services or assistance
relating to activities taken pursuant to this Agreement. POI further warrants
and represents that it has not been excluded from participation in any Federal
health care program as defined in United States Xxxxxxxxxx 00 X.X.X 0000x-0x(x)
(“Excluded Person”). POI further warrants and represents that no Excluded Person
has performed or rendered, or will perform or render, any services or assistance
relating to activities taken pursuant to this Agreement.
4.3 YM
warrants to POI that it has the authority to enter into this
Agreement.
5. POI’S
OBLIGATIONS
In
addition to POI's Obligations set forth in the Schedules, the Protocol and
elsewhere in this Agreement, POI shall have the following
obligations:
5.1
Before commencement of the Study, POI shall assign to the Study a Project
Manager and sufficient personnel, including CRAs, with suitable experience and
training to fulfill POI’s obligations under this Agreement. Any change in the
Project Manager thereafter must be reasonably acceptable to YM. YM may request
that POI remove any personnel, including the Project Manager whom XX xxxxx, in
its sole discretion, to be unfit or otherwise unsatisfactory. POI shall promptly
replace any such personnel with personnel with the necessary skills and
experience to fulfill POI’s Obligations under this agreement.
5.2 POI
shall apply to the Study systems of quality control designed to ensure that the
generation of data, and the recording and reporting of data is in compliance
with the Regulatory Requirements, Good Clinical Practice, the Protocol, and this
Agreement, in that order.
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CONFIDENTIAL
5.3 POI
shall use its best efforts to perform the Services within the time frames
specified in the Schedules.
5.4 POI
shall be responsible for all the legal and regulatory requirements, including
applicable guidelines, in all countries in which the Study will be conducted,
with the exception of (i) regulatory approval by Health Canada and the United
States Food and Drug Administration to conduct the Study, which will be obtained
by YM, and (ii) adverse event reporting to Health Canada and the United States
Food and Drug Administration which will be done by YM. Such responsibilities of
POI shall include, but are not limited to, the procurement and maintenance of
all consents, approvals, licenses, and operating certificates required to
conduct the Study in the applicable country, including translations, and the
approval of the Protocol and the informed consent forms by an IRB/EC. POI shall
also develop, comply with, and require its agents, employees and contractors to
comply with, policies and procedures designed to assure, at all times, that such
consents, approvals, licenses, and operating certificates remain in effect
throughout the Term. POI shall ensure that any institutions and investigational
teams retained to participate in the Study have the necessary staff and other
resources to carry out the Study in accordance with the timelines required by
YM. POI further agrees to ensure that any institutions and investigational teams
retained to participate in the Study have the expertise and experience, and the
necessary licenses, required to perform the Study efficiently and that such
Study shall be performed with care and skill and to the best of their ability
commensurate with such skill and experience and adhering at all times to
applicable laws.
5.5 POI
shall retain all material Study Documents and CRFs until this Agreement has
terminated and all Closeout Services have been performed. All Study Documents
and CRFs will be forwarded to YM after the Study is completed or upon
termination of this Agreement. YM shall be permitted full access to such Study
Documents and CRFs at any time upon written request to POI.
5.6 YM
shall have the right to visit and co-monitor a Study site or inspect and audit
any of the Study Documents and CRFs maintained by POI. All such visits and
inspections must be conducted during normal working hours on regular business
days, unless otherwise agreed. POI shall arrange access to the Study site as
soon as reasonably practicable following notification by YM.
5.7 POI
will provide YM with written status reports in accordance with POI’s
SOPs.
5.8 POI
shall notify YM after becoming aware of a Serious Adverse Event in accordance
with the procedure set out in Schedule 4.
5.9 POI
shall indemnify and save harmless YM, its officers, agents, and employees from
all third party suits, actions, losses, damages, claims, or liability of any
character, types, or description, including without limiting the generality of
the foregoing, all expenses of litigation, court costs, and reasonable attorney’s
fees arising from (i) injury or death to any person, or injury to property,
received or sustained by any person or persons or property, arising out of, or
occasioned by POI (or its agents or employees), in connection with its execution
or performance of services under this Agreement; (ii) any negligent wrongful act
or omission, reckless conduct or willful misconduct of POI, its employees,
agents, directors and officers; or (iii) any deviation by POI from the
terms of the Protocol or this Agreement or requirements or restrictions imposed
by an IRB/EC. The Investigators are not and shall not be deemed the agents of
POI for purposes of this Section 5.9. YM will notify POI of any claim or suit
which may be subject to the provisions of this Section 5.9 as soon as reasonably
practicable after receiving notice of the claim. POI shall have the sole right
to control and settle any such claim or suits, and YM shall make all reasonable
efforts to cooperate (at POI’s expense) as requested by POI in handling any such
claim or suit.
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6. YM’S
OBLIGATIONS
In
addition to YM’s Obligations set forth in the Schedules and elsewhere in this
Agreement, YM shall have the following obligations:
6.1 YM
shall provide POI, at no expense to POI (i) with all information and
documentation reasonably necessary for POI to perform its duties hereunder,
including but not limited to, all Clinical Trial Materials; and (ii) with all
advice, guidance, and assistance reasonably requested by POI to fulfill its
duties under this Agreement, including the schedules, and the
Protocol.
6.2 YM
shall be responsible for (i) obtaining regulatory approval from Health Canada
and from the United States Food and Drug Administration to conduct the Study in
Canada and in the United States, if necessary; and (ii) reporting adverse events
to Health Canada and to the United States Food and Drug Administration in
conformance with the legal and regulatory requirements.
6.3 YM
shall indemnify and save harmless POI, its officers, agents, and employees from
all third party suits, actions, losses, damages, claims, or liability of any
character, types, or description, including without limiting the generality of
the foregoing, all expenses of litigation, court costs, and reasonable attorneys’
fees for injury or death to any person, or injury to property (collectively,
“Claims”), received or sustained by any person or persons or property, arising
out of, or occasioned by the Investigational Product or the acts or omissions of
YM (or its agents or employees), in connection with the Study or their execution
or performance of this Agreement except to the extent that such Claims arise
from or are caused (i) by POI’s (its agents or employees) execution or
performance of services under this Agreement; (ii) any negligent wrongful act or
omission, reckless conduct or willful misconduct of POI, its employees, agents,
directors and officers; or (iii) any deviation by POI from the terms of the
Protocol or this Agreement or requirements or restrictions imposed by an IRB/EC.
POI will notify YM of any claim or suit which may be subject to the provisions
of this Section 6.2 as soon as reasonably practicable after receiving notice of
the claim. YM shall have the sole right to control and settle any such claims or
suits, and POI shall make all reasonable efforts to cooperate (at YM’s expense)
as requested by YM in handling any such claim or suit.
7.
LIMITATION OF LIABILITY
NOTWITHSTANDING
THE ABOVE, NEITHER PARTY, NOR THEIR AFFILIATES, NOR ANY OF THEIR RESPECTIVE
DIRECTORS, OFFICERS, EMPLOYEES, OR AGENTS SHALL HAVE ANY LIABILITY FOR ANY
SPECIAL, INCIDENTAL, INDIRECT, OR CONSEQUENTIAL DAMAGES, INCLUDING BUT NOT
LIMITED TO THE LOSS OF OPPORTUNITY, OR LOSS OF REVENUE OR PROFIT.
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8. CRO
COMPENSATION
8.1 YM
shall pay POI the amounts set forth in Schedules 1 and 2 for all services
provided and expenses incurred by POI pursuant to this Agreement, according to
the payment schedule set forth in Schedule 2. Amounts due are calculated in
British Pound Sterling or £ or BPS and are converted to US Dollars at the time
of invoicing or payment. All payments to be made in USD or $.
8.2 POI
shall submit invoices to YM upon the completion of each payment milestone event
set forth in Schedule 2. YM shall make full payment of such sums by wire or in
cleared funds to such bank account in the United States as POI may reasonably
specify from time to time, upon receipt of invoice (“Due Date”), without any
deduction, set off or withholding except any tax, duties or governmental charges
which YM is required by law to deduct or withhold. Any amounts which remain
unpaid for thirty (30) days or more after the Due Date shall bear interest at
the rate equal to 10% per annum. Interest shall be computed on the basis of a
365 or 366-day year, as the case may be. If any amounts remain unpaid for sixty
(60) days or more after the Due Date, POI shall have the right to discontinue
all work and services under this Agreement until such amounts are paid in
full.
8.3 If YM
is required by law to make any tax deduction or withholding, YM shall provide
reasonable assistance as requested by POI to assist POI to claim exemption from,
or if that is not possible a credit for, the deduction or withholding under any
applicable double taxation or similar agreement. YM shall also supply POI from
time to time with proper evidence as to the deduction or withholding and payment
over of the tax deducted or withheld.
8.4 YM
shall reimburse POI for all reasonable expenses incurred by POI in its
performance of the Services, including but not limited to, travel expenses
incurred by POI in connection with initiation visits, monitoring visits, and
closeout visits and in connection with attendance at Project Meetings and
Investigators’ Meetings. YM shall also reimburse POI for all couriers, shipping,
regulatory fees, customs, supplies, related drugs, outside or contracted
services, including Investigator payments or grants, and other similar expenses
incurred by POI in its performance of its duties under this Agreement.
Notwithstanding the foregoing, YM shall not be responsible for any costs
described in this Section 8.4 that exceed the amounts budgeted for such expenses
in Schedule 1, without prior written approval being obtained from YM. Any
amounts approved by YM in excess of those specified in Schedule 1, shall be
separately invoiced to YM and YM shall pay these invoices according to the terms
of Paragraph 8.2.
9.
AUDIT
9.1 POI
shall maintain and shall cause to be maintained, complete and accurate books of
account containing all particulars that may be necessary for the purpose of
calculating any fees, expenses or other costs (collectively, the “Service
Costs”) relating to the Services and any deliverables as set out in Schedule 1.
Such books of record shall be kept at its principal place of
business.
9.2 Upon
the written request of YM, POI shall permit YM or its third party independent
auditors to have access during normal business hours, upon ten (10) days’ notice
to POI, to such records, including working papers and supporting documents, of
POI, its independent contractors and agents as may be reasonably necessary to
verify the accuracy of the Service Costs.
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9.3 If
any audit reveals any overpayment of Service Costs, POI shall forthwith pay the
amount of the overpayment to YM; provided however, that, in the event that POI
shall not be in agreement with the amount of the overpayment, such matter shall
be resolved pursuant to the provisions of Section 14 herein.
9.4 If
any audit reveals any underpayment of Service Costs, YM shall forthwith pay the
amount of the underpayment to POI, provided however, that, in the event that YM
shall not be in agreement with the amount of the overpayment, such matter shall
be resolved pursuant to the provisions of Section 14 herein.
9.5 Both
parties shall treat all financial information subject to review under this
Section 9 in accordance with the confidentiality provisions of this
Agreement.
9.6 The
costs of conducting any audit hereunder shall be borne by YM unless the audit
reveals an overpayment of Services Costs of greater than 5%. Any such audit fees
not to exceed £15,000 (BPS British Pound Sterlings).
10.
CLINICAL STUDY AGREEMENT NEGOTIATION
Where
possible, POI will endeavor to use the Clinical Study Agreement template
attached at Schedule 3 to this Agreement when entering into agreements with any
investigational teams or sites engaged for the purpose of conducting a clinical
trial on the Investigational Product. POI shall not make any modification to the
Clinical Study Agreement template attached at Schedule 3 or enter into any
clinical study agreement using such modified form of agreement without YM’s
prior written approval. In any case, POI shall not enter into any agreement with
any investigational teams or sites engaged for the purpose of conducting a
clinical trial on the Investigational Product, without YM’s approval of the form
and content of the agreement.
11.
INSURANCE
11.1 YM
and POI shall each maintain, at its sole cost and expense, insurance coverage
with a reputable insurer (which shall be either occurrence based or claims made
coverage) in an amount usual and customary for companies engaged in activities
as contemplated by this Agreement. All such insurance shall be in place before
the first patient is enrolled in the Study. Each shall designate the other party
as an additional named insured on all such policies, and an endorsement shall be
made on each such policy prohibiting the insurer from canceling the policy for
any reason or substantially modifying its terms without first giving the other
party at least twenty-eight (28) days written notice of its intention to do
so.
If either
party maintains a claims-made policy and this Agreement expires or terminates
for any reason, then that party shall either continue to maintain the same or
higher coverage with the same insurance carrier for a period of four (4) years
thereafter; or shall purchase “Tail Coverage” effective until the fourth (4th)
anniversary date of the expiration or termination of this Agreement or obtain
and maintain “Prior Acts” coverage equivalent in time and coverage as the “Tail
Coverage” described herein.
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11.2 Upon
request by either party, the other party shall provide evidence of that party’s
compliance with this Section.
12.
CONFIDENTIALITY
12.1
Except as specified in the following Section 12.2, each of the parties agrees
(i) that it shall not disclose any Confidential Information of the other party
to other persons without the express written authorization of the other party;
(ii) that such Confidential Information shall not be used in any way detrimental
to the other party or for any purpose not related to the performance of the
Services or the Study; and (iii) that the parties will keep such Confidential
Information confidential and will ensure that its affiliates and advisors who
have access to such Confidential Information comply with these non-disclosure
obligations.
12.2
Notwithstanding the foregoing, the parties may disclose Confidential Information
to (i) those of its representatives, including, but not limited to the other
party’s legal, financial and accounting advisors, who need to know Confidential
Information for the purpose of conducting this Study, it being understood and
agreed by the parties that such representatives will be informed of the
confidential nature of the Confidential Information, will agree to be bound by
this Section 12, and will be directed by the respective party not to disclose to
any other person any Confidential Information; and (ii) the FDA, an IRB/IEC, or
comparable governmental or professional body with jurisdiction over the Study
provided such disclosure is requested by the respective governmental or
professional body or is required in order to satisfy Section 5.4.
12.3 In
the event that either party determines that it is required by law to disclose
the other party’s Confidential Information, or such disclosure is in response to
a subpoena or a similar legal process, such disclosure shall be permitted
provided that the other party required to make such disclosure promptly notifies
the other party and assists the other party in obtaining a protective order or
other appropriate remedy.
13.
INTELLECTUAL PROPERTY
13.1 POI
acknowledges and agrees that any and all intellectual property rights
(including, but not limited to, inventions, discoveries, improvements and
know-how, whether patentable or not) that may arise or be conceived during, or
are related to, the Study , including without limitation all data generated in
the course of the Study, completed Case Report Forms and all Clinical Trial
Materials (hereinafter the “Intellectual Property”) shall belong solely to YM.
POI shall cooperate with YM, and shall use its best efforts to ensure that any
institutions and investigational teams which participate in the Study, including
their employees and agents, cooperate with YM, in obtaining assignments or other
documents required to transfer to YM all Intellectual Property. In addition, POI
shall use its best efforts to ensure that any institutions and investigational
teams which participate in the Study, including their employees and agents,
cooperate with YM, at YM’s sole expense, in preparing patent applications
relating to the Intellectual Property, where required.
13.2 The
Parties agree that POI has no rights to publish or present, at any time, the
data generated in the course of the Study.
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CONFIDENTIAL
13.3 YM
acknowledges that, as between POI and YM, any and all intellectual property
rights in works authored by POI before the Effective Date of this Agreement and
works authored by POI independent of the Study shall belong to POI.
14.
ARBITRATION
All
disputes, disagreements, controversies, questions or claims arising out of or
relating to this Agreement and all other agreements entered into pursuant to the
terms of this Agreement, including, without limitation, with respect to their
formation, execution, validity, application, interpretation, performance,
breach, termination or enforcement (“Disputes”) shall be determined by
arbitration under the International Commercial Arbitration
Act (Ontario) (the “International Act”), provided that:
14.1 any
hearing in the course of the arbitration shall be held in Toronto,
Ontario;
14.2 the
number of arbitrators shall be one;
14.3 any
award or determination of the arbitrator shall be final and binding on the
parties and there shall be no appeal on any ground, including, for greater
certainty, on the ground of alleged errors of law. For greater certainty,
Article 34 of the International Act shall apply to an arbitration under this
section 14;
14.4
despite Article 26 of the International Act, the arbitrator shall not, without
the written consent of all parties to the arbitration, retain any
expert;
14.5 an
arbitrator may apportion the costs of the arbitration, including the reasonable
fees and disbursements of the parties, between or among the parties in such
manner as the arbitrator considers reasonable, provided that an arbitrator shall
not award costs on a distributive basis;
14.6 all
awards for the payment of money shall include prejudgment and postjudgment
interest in accordance with sections 127 to 130 of the Courts of Justice Act
(Ontario) with necessary modifications; and
14.7 all
matters in relation to the arbitration shall be kept confidential to the full
extent permitted by law, and no individual shall be appointed as an arbitrator
unless he or she agrees in writing to be bound by this dispute resolution
provision.
15.
NON-SOLICITATION OF STAFF
During
the term of this Agreement and for a period of twelve months following its
termination or expiration, YM shall not directly or indirectly (i) solicit or
entice any employee or contractor of POI with whom it comes into contact as a
result of participation in the Study, to become employees of YM or any other
person or entity; or (ii) approach any such employee or contractor for such
purpose or authorize or approve the taking of such action by any other
person.
16. TERM
AND TERMINATION
16.1 This
Agreement shall commence on the Effective Date and, unless terminated pursuant
to this Section 16, shall continue until such time as the Services and Closeout
Services have been completed. This Agreement does not cover any services
required for long-term patient follow up. The parties shall endeavour to enter
into a separate agreement for such services.
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CONFIDENTIAL
16.2 This
Agreement may be terminated upon the mutual, written consent of both parties.
This Agreement may also be terminated by YM without cause upon thirty (30) days
prior written notice to the other party.
16.3
Either party may immediately terminate this Agreement for cause, upon written
notice to the other party stating the date of termination, pursuant to the
following:
16.3.1
Termination by POI. POI
may terminate this Agreement for cause upon the occurrence of any of the
following events:
(i) YM
fails to maintain the insurance coverage required by Section 11.1;
(ii) The
FDA, IRB/EC, or any regulatory authority with jurisdiction over the Study
suspends or revokes any consent, approval, license, or operating certificate
required to conduct the Study;
(iii) YM
breaches any material provision of this Agreement, other than those specifically
referenced in this Section 16.3.1, and fails to remedy that breach within 30
days after receiving notice of such breach; or
(iv) YM
files a petition for the appointment of a receiver in liquidation or a trustee
with respect to itself or any of its property; or any person other than YM files
a petition for the appointment of a receiver in liquidation or a trustee with
respect to YM in bankruptcy, insolvency, or reorganization, compromise,
adjustment or other relief relating to the relief of debtors, and such
involuntary petition is not vacated or set aside or stayed within 60 days from
YM’s receiving notice of such petition.
16.3.2
Termination by YM: YM
may terminate this Agreement for cause upon the occurrence of any of the
following events:
(i) The
FDA, IRB/EC, or any regulatory authority with jurisdiction over the Study
suspends or revokes any consent, approval, license, or operating certificate
required to conduct the Study;
(ii} The
occurrence of a Serious Adverse Event which causes the study to be terminated
due to safety concerns by the Data Safety Management Board;
(iii) If
POI enters into a Clinical Trial Agreement with an Investigator relating to the
Study, and the Investigator or any member of the Investigator’s staff fails to
possess all qualifications, training, and licenses necessary to perform the
duties and obligations of that individual under that agreement or fails in any
material manner to abide by the provisions of the Regulatory Requirements or
this Agreement; provided, however, that POI may cure any such deficiency by
removing forthwith the affected individual from providing services under this
Agreement;
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CONFIDENTIAL
(iv) POI
breaches any material provision of this Agreement, other than those specifically
referred to in this Section 16.3.2, and fails to remedy that breach within 30
days after receiving notice of such breach;
(v) POI
files a petition for the appointment of a receiver in liquidation or a trustee
with respect to itself or any of its property; any entity POI controls makes a
-voluntary assignment for the benefit of creditors or files a petition in
bankruptcy or insolvency or for reorganization, compromise, adjustment, or other
relief; or if any person other than POI files a petition for the appointment of
a receiver in liquidation or a trustee with respect to POI or any entity it
controls in bankruptcy, insolvency, or reorganization, compromise, adjustment or
other relief relating to the relief of debtors, and such involuntary petition is
not vacated or set aside or stayed within 60 days from POI’s receiving notice of
the petition; or
(vi) POI
is unable to perform its obligations under this Agreement due to a Force Majeure
Event for a period greater than thirty (30) days.
16.4 In
the event of any change or reinterpretation of a Regulatory Requirement, the
adoption of any new law or regulation, or the initiation of an enforcement
action with response to laws, regulations, or guidelines applicable to this
Agreement, any of which shall affect the legality of this Agreement, the parties
agree to negotiate in good faith to amend this Agreement to comply with the
offended law or regulation. If the parties do not agree to such amendment within
30 days prior to the effective date of the offended law or regulation (or such
earlier time as may be required to comply), then either party may terminate this
Agreement immediately by giving written notice to such effect to the other
party.
17.
CONSEQUENCES OF TERMINATION
17.1 Upon
termination of this Agreement, POI shall immediately provide to YM complete and
up-to-date written records accounting for the full amount of Investigational
Product dispensed, and the amount of unused Investigational Product remaining in
the possession of POI, or the investigational teams or sites participating in
the Study. POI shall, and shall ensure that the investigational teams or sites
participating in the Study, return without delay any unused quantities of the
Investigational Product, including samples, unless YM requests that such
Investigational Product be destroyed, in which case POI shall arrange for such
destruction and provide appropriate proof to YM that such destruction has
occurred.
17.2 The
termination of this Agreement for any reason shall not affect any right or
remedy existing hereunder prior to the effective date of
termination.
17.3 Upon
early termination of this Agreement pursuant to Sections 16.2, 16.3, or 16.4, YM
shall continue to pay POI the amounts set forth in Schedules 1 and 2 for all
services actually provided and expenses actually incurred by POI prior to the
date of termination of this Agreement. Without limiting the foregoing, upon
termination of this Agreement, YM shall, in addition to all CRO Compensation
then due, compensate POI, as specified in Schedules 1 and 2, for all Closeout
Services required to terminate and closeout the Study, including but not limited
to, any activities necessary to satisfy the requirements of any governmental,
regulatory, or professional authority with jurisdiction over the Study. Further,
upon termination of this Agreement by YM prior to the completion of the Study
pursuant to Section 16.2, YM shall pay POI a termination fee that shall equal
10% of the remaining unbilled compensation, if any, pursuant to Section 8.1 and
Schedules 1 and 2 as of the date of termination. This termination fee shall be
paid, in part, to compensate POI for having to reassign its personnel and incur
out-of-pocket expenses not covered by Section 8.1 and Schedules 1 and
2.
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22 February,
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17.4 In
the event that, at the date of termination of this Agreement, the amount already
paid by YM to POI exceeds the total of: (1) the cost for services actually
provided by POI up to the date of termination, (2) expenses actually incurred by
POI up to the date of termination, (3) the cost for the Closeout Services; and
(4) the termination fee according to Section 17.3, if applicable, then the
excess amount shall be immediately refunded to YM.
17.5 In
no event shall the amount payable to POI by YM pursuant to this Agreement exceed
the maximum amounts specified in Schedule 1 or 2, without the prior written
agreement of the Parties.
18.
REPETITION OF THE STUDY
In the
event of a material error by POI as agreed to by POI in the performance of the
Services, POI shall repeat the applicable Services upon YM’s request at no
additional expense to YM.
19.
DELAYS
19.1 YM
may, in its sole discretion, require POI to delay or suspend Services. If (a) YM
requests such a delay due to no fault of POI; and (b) YM requests that POI staff
continue to be assigned to the project during the period of such delay or
suspension; the parties shall negotiate in good faith a monthly maintenance fee
payable by YM during the period that Services are suspended and staff continue
to be assigned. While the monthly maintenance fee is being paid, payments due as
outlined in Schedules 1 and 2 shall continue to be payable. Such delay shall
last no longer than six (6) months, after which time POI shall have the right to
terminate this Agreement.
20.
GENERAL PROVISIONS
20.1 This
Agreement sets forth the entire agreement and understanding among the parties as
to the matters contained therein, and merges and supersedes any prior
discussions, agreements, and understanding of every kind and nature relating
thereto.
20.2 Any
amendment of or modification to this Agreement shall become effective only if it
is in writing and executed by the parties.
20.3 This
Agreement shall be binding upon, and inure to the benefit of, the parties and
their respective legal representatives, trustees, receivers, successors and
permitted assigns.
20.4
Except as otherwise specified in this Agreement or otherwise agreed to by the
parties in writing, all notices, requests, demands, and other communications
provided for in this Agreement shall be in writing in English and shall be
deemed to have been given at the time when personally delivered, or mailed by
registered or certified mail, return receipt requested, to the address of the
other party stated below or to such other address as any such party may have
fixed by notice, provided, however, that any notice of change of address shall
be effective only upon receipt by addressee.
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All
notices to YM shall be addressed to:
Xxxxx
X.X. Xxxxx
President
and CEO
0000
Xxxxxxx Xxxxx
Xxxxxxxx
00, Xxxxx 000
Xxxxxxxxxxx,
Xxxxxxx X0X0X0 Xxxxxx
If
notices or communications by telephone or facsimile are specifically authorized
in this Agreement or otherwise agreed to by the parties in writing, calls to YM
shall be placed and facsimiles to YM shall be sent to the following
numbers:
Phone:
(000) 000-0000
Fax:
(000) 000-0000
All
notices to POI shall be addressed to:
Xxxx
Xxxxx
Executive
Vice President
Pharm-Olam
International Ltd.
000 X Xxx
Xxxxxxx Xxxxxxx, Xxxxx 000,
Xxxxxxx,
XX 00000
Xxxxxx
Xxxxxx
If
notices or communications by telephone or facsimile are specifically authorized
in this Agreement or otherwise agreed to by the parties in writing, calls to POI
shall be placed and facsimiles to POI shall be sent to the following
numbers:
Phone:
(000) 000-0000,
Fax:
(000) 000-0000
The
parties shall give notice to each other of any change of their address or
telephone, facsimile, or similar number at the earliest possible
opportunity.
20.5 All
agreements of the parties, as well as any rights or benefits accruing to them,
pertaining to a period of time following the termination or expiration of this
Agreement or any of its provisions, including but not limited to Paragraph 5.9,
6.3, and Sections 7 through 15, and 17, shall survive such termination or
expiration hereof and shall not be merged.
20.6 The
waiver by any party of breach or default by any other party shall not operate as
a waiver of a continuing or subsequent breach or default of the same or a
different nature or kind.
20.7 If
any provision of this Agreement or the application of any such provision to any
person or circumstance is held invalid, the remainder of this Agreement and the
application of such provision to other persons or circumstances shall not be
affected unless the invalid provision substantially impairs the benefits of the
remaining provisions of this Agreement.
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22 February,
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CONFIDENTIAL
20.8 No
party may assign this Agreement or its rights and duties hereunder, without the
prior written consent of the other party, except that YM may assign this
Agreement to a purchaser or acquirer of substantially all of the business to
which this Agreement relates.
20.9 The
provisions of this Agreement shall be self-executing and shall not require
further agreement by the parties except as may otherwise be specifically
provided in this Agreement; provided, however, that, at the request of a party,
the other party shall execute such additional instruments and perform such
additional acts as may be reasonably necessary to effectuate this
Agreement.
20.10
This Agreement may be executed in counterpart originals, with each counterpart
to be deemed an original, but all counterparts together shall constitute a
single instrument.
20.11 In
the event that performance by a party of any of its obligations under the terms
of this Agreement shall be interrupted or delayed by a Force Majeure Event, that
party shall be excused from such performance for the same amount of time as such
occurrence shall have lasted or such period of time as is reasonably necessary
after such occurrence abates for the effects thereof to have
dissipated.
21.
APPLICABLE LAW
This
Agreement shall be governed by and be construed under the laws of Ontario,
Canada without giving effect to its choice-of-law rules, and exclusive venue of
any action or other proceeding that may be brought or arise out of, in
connection with, or by reason of this Agreement shall be in Ontario,
Canada.
IN
WITNESS WHEREOF, this Agreement is executed by the parties hereto and is
effective as of the day and year first above written.
|
YM
BIOSCIENCES, INC.:
|
|||||
|
By:
|
/s/
Xxxxx X.X. Xxxxx
|
Date: 8/12/05
|
|||
|
Xxxxx
X.X. Xxxxx, its President and CEO
|
|||||
|
PHARM-OLAM
INTERNATIONAL LTD.:
|
|||||
|
By:
|
/s/
Xxxx Xxxxx
|
Date:
2/22/05
|
|||
|
Xxxx
Xxxxx, Executive Vice-President
|
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MASTER
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Schedule
3
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INVESTIGATOR
AGREEMENT
This
Agreement is entered into as of the date on the signature page, between
Pharm-Olam International, Ltd., YM BioSciences Inc. and undersigned
parties:
|
Pharm-Olam
International, Ltd
|
Name
of Investigator
|
||
|
Investigator:
|
|||
|
000
X Xxx Xxxxxxx Xxxxxxx, Xxx 000
|
|||
|
Address:
|
Houston,
TX
|
Institution:
|
Name
of clinic/hospital
|
|
77060
USA
|
|||
|
Address:
|
|||
|
Clinic
address
|
|||
|
Tel
No:
|
(000)
000-0000
|
Tel
No:
|
(
)
|
|
Fax
No:
|
(000)
000-0000
|
Fax
No:
|
(
)
|
|
Xxxxx
X.X. Xxxxx, President & CEO
|
|||
|
Address:
|
0000
Xxxxxxx Xxxxx
|
||
|
Building
11, Suite 400
|
|||
|
Mississauga,
Ontario
|
|||
|
Canada
|
|||
|
X0X
0X0
|
|||
|
Tel
No:
|
000.000.0000
|
||
|
Fax
No:
|
000.000.0000
|
Pharm-Olam
International, Ltd. (hereafter referred to as “POI”) and YM BioSciences Inc.
(hereafter referred to as “YM”) desire PHYSICIAN NAME (hereafter
referred to as “the investigator”) to conduct the following clinical trial: ‘A
Pharmacokinetic Interaction Phase I, Open Label, Single Centre Study Evaluating
the Plasma Pharmacokinetics of Taxotere Alone and in Combination with YMB1002 in
Patients with Advanced Metastatic Breast Cancer or Other Advanced Cancer
Suitable for Treatment with Taxotere’ sponsored by YM. POI is a contract research
organization retained by YM for this
study.
The study
is planned to start in JANUARY
2005 all patients should be enrolled by MARCH 2005. These dates are
based on the current time-frame specified by YM.
The
investigator agrees to the following:
1. Scope of
work
The study
will be performed and directed by the investigator and his/her co-workers, under
his/her immediate supervision, according to the final, signed protocol and this
agreement. The investigator possesses the required skill, experience and
knowledge, staff and access to patients, to conduct the study. The investigator
shall: 1) provide an acceptable facility throughout the clinical trial: 2)
maintain adequate and confidential records of patients identification, clinical
observations, laboratory tests, study drug receipts and disposition: 3) complete
Case Report Forms (CRFs): and 4) deliver all unused drug supplies, all CRFs,
Serious Adverse Event reports and any other study related information to POI, YM or regulatory agencies, as
requested and in a timely manner.
|
Date
of template: 21 December 2004
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Date
of Agreement:
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MASTER
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The
investigator shall conduct the study to conform with local law and regulations,
institutional regulations, and according to the Declaration of Helsinki (2000
Edinburgh Scotland amendment) and applying consistently Principles of Good
Clinical Practice (GCP) as required by the ICH-CPMP Guidelines
(1996).
The
investigator will not concurrently conduct any study that may conflict with or
negatively impact upon the goals of this study.
The
investigator represents and warrants that he and the staff which will be
involved in this study have the necessary licenses and qualifications to conduct
the study.
2. Regulatory
responsibilities
The
investigator will obtain a signed Letter of Approval for the study and for the
Informed Consent Form from the appropriate Independent Ethics Committee prior
(IEC) to the study start and provide POI with a copy of the
approval documentation. The investigator will also provide a list of the
Committee members at the time when approval was given and their
titles/occupation/positions. The investigator will provide POI with the copy of any
direct correspondence with Ethics Committee and/or Regulatory Bodies concerning
the review and approval of study documentation. The investigator shall ensure
that written informed consent is obtained from each patient prior to enrolment
in the study. In order to support continuous review of the study by the IEC, the
investigator will periodically update the committee on trial progress, including
patient recruitment, safety issues, new information, etc. In addition, the
investigator will submit for review by the IEC any amendments to the study
documentation, which may impact upon patient rights, safety and/or
well-being.
3. Clinical
data
All
information entered into the Case Report Forms should reflect the patient’s true
condition. The investigator shall review all CRFs and check the data against all
pertinent information in the patients clinical records for accuracy and
completeness of information, legibility of entries, correct any erroneous data,
record use of concomitant drugs, report adverse events, concurrent illnesses and
document reasons for any missing visits or examinations.
All study
related data and information will be the property of YM and may be freely utilized
by YM.
4. Adverse
experiences
The
investigator agrees to notify POI and/or YM within a maximum
of 24 hours (whenever possible immediately by telephone or fax) of any serious
(fatal, life threatening, requiring or prolonging hospitalisation, resulting in
persistent or significant disability, representing a significant hazard, a
congenital anomaly, or other medically important condition) and/or unexpected
adverse events. An SAE form with all available information should be submitted
within 24 hours to YM
and POI. Details should
be also noted on the appropriate form in the CRF, followed up and investigated
further when necessary. All events should be followed-up until resolution and
any new information should be promptly submitted to YM and POI on a follow-up SAE form.
The investigator should also notify the local Ethics Committee, within the time
frame specified by the Ethics Committee.
5. Monitoring and data
verification
According
to ICH-GCP guidelines, data entered on to the CRF have to be monitored and
verified against source documents for completeness, accuracy and consistency.
For complying with these regulations the POI study monitor will require
access to CRFs, patients clinical notes and other relevant patient information.
The investigator agrees to allow direct access to hospital records, etc., for
the purpose of Source Document Verification (SDV) by the POI study monitor. The
investigator also agrees to provide any missing information in the CRFs, correct
any data errors and complete
hospital records, for 100% consistency with data entered into the CRFs.
Hospital records should be completed before CRFs.
|
Date
of template: 21 December 2004
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of Agreement:
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MASTER
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Schedule
3
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6. Audit and
inspection
The
investigator will permit access to the facilities and provide patient data and
all study related information for the purpose of the Quality Assurance audit by
POI or YM personnel (or
their delegates) or to Regulatory Authorities representatives for the purpose of
inspection within usual working hours.
7. Retention of the
documents
The
investigator agrees to retain all study related documentation in secure, fire
retardant storage, for at least 2 years after the last approval of a marketing
application (and there are no pending or contemplated applications), or at least
2 years after clinical development of the medication has been terminated. If
local regulations require a longer period of retention, then these will take
precedence. YM will
inform the investigator when retention of trial documents is no longer
required.
8.
Confidentiality
The
investigator agrees that he/she and all his/her co-workers involved, will treat
all information related to the study as confidential to YM. Such information will be
kept in confidence and not used except in connection with the study and will not
be disclosed, without prior written consent of YM, to any third party other
than those who have a need for such information in conjunction with the approval
or conduct of the study. The information will remain confidential for 10 years
following study completion.
9.
Publications
All
clinical studies carried out by YM will be published wherever
possible. Any proposed publication or presentation by the investigator is
subject to the written approval by YM in advance. A copy of the
proposed publication will be sent to YM at least 30 days before the
intended date of submission/presentation for YM reference and comment. The
investigator agrees to comply with any amendments deletions or comments made by
YM , including delay or
non-publication of the article, if requested. YM will be included as
co-author of any publication or presentation. The obligations described in this
Section 9 shall survive the expiration or earlier termination of this
Agreement.
10. Amendments and
Addenda
This
agreement should not be amended or modified except in writing signed by POI.
11.
Invention
YM shall solely own all
intellectual property (including but not limited to, patentable and
non-patentable inventions, discoveries, improvements and know-how) made or
conceived in the course of or as a result of the study. The Investigator is
obliged to disclose any inventions or discoveries as a result of the study to
YM. The Investigator
hereby assigns and agrees to assign to YM all right, title and
interest in any such intellectual property and agrees to cooperate with YM, at YM’s expense, in preparing,
filing and executing patent applications and any and all other documents to
secure YM’s intellectual
property rights and to obtain, maintain, and enforce all worldwide rights in any
such intellectual property. Investigator shall promptly turn over to YM any and all records
relating to all such intellectual property and shall cause his/her co-workers
and staff involved in the study to comply with the terms and conditions of this
Section 11. The obligations described in this Section 11 shall survive the
expiration or earlier termination of this Agreement.
|
Date
of template: 21 December 2004
|
Page
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Date
of Agreement:
|
|
MASTER
|
Schedule
3
|
12.
Termination
YM reserves the right to
terminate the study prematurely for reasonable causes at a single centre or the
entire study for all centers at any time, which effectively would also terminate
their contract with POI.
If this situation should arise, POI reserves the right to
terminate this Investigator’s agreement. In this event, payments will be made on
pro-rata basis, for work done prior to termination of the agreement. The
Investigator may also terminate this agreement by giving POI 30 days notice if he/she
is no longer able to perform the study only for reasons beyond his/her control.
POI may terminate this
agreement if the investigator fails to comply with their obligations,
responsibilities and the terms and conditions of this Agreement and the
Protocol.
If this
study is terminated prematurely, the investigator agrees to furnish to POI all
CRFs completed and/or partially completed up to the date of termination of the
study, as well as all other study related materials including, but not limited
to study drug.
POI reserves the right to
instruct the Investigator not to enroll any patients into the study, in which
case payments will be made according to the payment structure in section 14 for
time already spent on the study.
POI also reserves the right to
instruct the investigator to enroll fewer patients than the number agreed at the
time of the signature of this Investigator’s agreement, in which eventually the
payment due to the Investigator will be made on a pro-rata basis.
13. Liability and
indemnification
The
investigator acknowledges that he is acting as an independent contractor and not
as an employee of POI.
YM shall indemnify the
investigator in accordance with the letter of indemnification. YM shall have no
indemnification, obligation or liability and the investigator shall indemnify,
defend and hold YM and
POI and their employees
and contractors harmless against any loss, claim, demand, costs and expenses, or
damage resulting from:
|
a.
|
Failure of the investigator or
his co-workers to adhere to the protocol or agreed amendments or written
recommendations and instructions relative to the administration of the
study drug.
|
|
b.
|
Failure of investigator or his
co-workers to comply with local law or regulations applicable to the
performance of its obligations under this
agreement.
|
|
c.
|
Negligent act or omission or
willful misconduct.
|
14.
Payments
POI will pay $4,650.00 for each completed and evaluable
patient. An evaluable patient is defined as follows:
a.
patients fulfill all selection criteria
b.
there are no protocol violations
c.
all examinations are conducted according to the study schedule
d.
CRFs are completed accurately and only in
English
Up to
30 eligible patients
will be DOSED in the
study by the study site.
|
Date
of template: 21 December 2004
|
Page
4 of 6
|
Date
of Agreement:
|
|
MASTER
|
Schedule
3
|
POI AND YM will pay according
to the schedule below:
|
VISIT
NO
|
AMOUNT US$
|
|||
|
BASELINE
|
300
|
|||
|
COURSE
1
|
250
|
|||
|
ICU
Unit day for PK sampling
(9-10
samples/24h)
|
550
|
|||
|
Day
2 PK sampling
|
150
|
|||
|
Day
3 PK sampling
|
150
|
|||
|
COURSE
2
|
300
|
|||
|
ICU
Unit day for PK sampling
(9-10 samples/24h) |
550
|
|||
|
Day
2 PK sampling
|
150
|
|||
|
Day
3 PK sampling
|
150
|
|||
|
COURSE
3
|
300
|
|||
|
COURSE
4
|
300
|
|||
|
COURSE
5
|
350
|
|||
|
COURSE
6
|
350
|
|||
|
COURSE
7
|
350
|
|||
|
FUp
Day l6O
|
250
|
|||
|
FUp
Day 190
|
200
|
|||
|
TOTAL
|
4650
|
|||
For
patients who withdraw/are withdrawn from the study, every effort should be made
to ensure the patient is assessed at the time of withdrawal and a final
termination visit is performed. The investigator will be responsible for the
payment of any local taxation (if applicable).
Payments
will be made quarterly according to monitored visits.
Study
Products:
All study
products (DPPE, taxotere, doxorubicin, epirubicin, cyclophosphamide) will be
provided or fully reimbursed by the sponsor.
Diagnostics:
Study-specific
diagnostics will be reimbursed to the investigator site upon receipt of
quarterly invoices for the following procedures and conditions:
|
|
·
|
The diagnostics tests/procedures
were required by the protocol,
and
|
|
|
·
|
Are not routinely included in the
standard of care assessments for non-study patients at this site,
and
|
|
|
·
|
Are not covered by the subject’s
health insurance or other health benefits payments to the site,
and
|
|
|
·
|
Do not exceed the below maximum
amounts per procedure.
|
|
Maximum Reimbursement
for Diagnostics
|
US$
|
|||
|
CT
Scan or Abdominal US
|
$
|
300
|
||
|
Bone
scan
|
$
|
100
|
||
|
MUGA
scan
|
$
|
125
|
||
15.
Counterparts
This
Agreement may be signed by facsimile and in counterparts and each of such
counterparts will constitute an original document and such counterparts, taken
together, will constitute one and the same document.
|
Date
of template: 21 December 2004
|
Page
5 of 6
|
Date
of Agreement:
|
|
MASTER
|
Schedule
3
|
To
demonstrate the full agreement with this document the investigator should sign
below and write his/her
initials in the right hand bottom corner of each page, then return the
signed copy to POI. The
original should be retained for the investigator’s record
|
The
Investigator
|
An
authorised signatory of
Pharm-Olam
International, Ltd
|
|||
|
Name:
|
Name:
|
|||
|
Signature:
|
Signature:
|
|||
|
Date:
|
Date:
|
|||
|
An
authorised signatory of
|
||||
|
Name:
|
||||
|
Signature
|
||||
|
Date:
|
|
|||
17. Payment
procedures:
|
—
|
transfer
to specified bank account
|
|
—
|
other
(please specify or discuss with POI
monitor) |
|
Bank:
|
|
|
Address
of the Bank:
|
|
|
Account
No:
|
|
Date
of template: 21 December 2004
|
Page
6 of 6
|
Date
of Agreement:
|
SCHEDULE
2
Pharm-Olam
International
Payment
Schedule
Study:
Taxotere PK YMB Study YB1002-203
Number
of Patients: 30 Randomised
Countries: Serbia (2 sites)
Date: 25th January 2005
Total
Contracted Services
|
£114,333
|
$217,232
|
|||||||
|
1 20% due
now
|
22,867.00 | 43,446.00 | ||||||
|
2
Monthly Jan 05
|
10,163.00 | 19,310.00 | ||||||
|
3
Monthly Feb 05
|
10,163.00 | 19,310.00 | ||||||
|
4
Monthly Mar 05
|
10,163.00 | 19,310.00 | ||||||
|
5
Monthly Apr 05
|
10,163.00 | 19,310.00 | ||||||
|
6
Monthly May 05
|
10,163.00 | 19,310.00 | ||||||
|
7
Monthly Jun 05
|
10,163.00 | 19,310.00 | ||||||
|
8
Final Payment: To be paid when YM Bioscience, Inc. recieves the final
report and all appropriate documents.
|
30,487.00 | 57,926.00 | ||||||
|
Total
Payments
|
114,332.00 | 217,232.00 | ||||||
|
Page
1 of 1
|
CONFIDENTIAL
|
SCHEDULE
1
Pharm-Olam
International
Clinical
Services Cost
Study:
Taxotere PK YMB Study YB1002-203
Number
of Patients: 30 Randomised
Countries: Serbia (2
sites)
Date:
25th January 2005
|
Number of Hours per task per position
|
|||||||||||||||||||||||||||||
|
Task
|
Position
|
Admin
|
CRA
|
PM
|
OA Auditor
|
||||||||||||||||||||||||
|
No.
|
Hourly Rate
|
£26
|
£50
|
£66
|
£81
|
Cost (£)
|
Cost (US$)
|
Assumptions
|
|||||||||||||||||||||
|
1.
|
Selection
of Investigators
|
||||||||||||||||||||||||||||
|
Investigator
Identification
|
£ | 0 | $ | 0 |
Using
same sites as Doxirubicin study
|
||||||||||||||||||||||||
|
Approval
of Sites
|
£ | 0 | $ | 0 |
“
|
||||||||||||||||||||||||
|
Assemble
pre-study documents and distribute to sites
|
£ | 0 | $ | 0 |
“
|
||||||||||||||||||||||||
|
2.
|
Documentation
|
||||||||||||||||||||||||||||
|
Protocol
Review
|
12 | 4 | £ | 1,116 | $ | 2,120 |
12
hrs PM and 4 hrs QA to review final protocol
|
||||||||||||||||||||||
|
CRF
Review
|
16 | £ | 1,056 | $ | 2,006 |
16
hrs for PM to comment on design before finalisation
|
|||||||||||||||||||||||
|
Generation
of master PIL/ICF
|
£ | 0 | $ | 0 |
Assume
not required
|
||||||||||||||||||||||||
|
PK
Protocol development
|
£ | 0 | $ | 0 |
None
|
||||||||||||||||||||||||
|
Translations
|
0 | £ | 0 | $ | 0 |
(see
translation table for assumptions and breakdown)
|
|||||||||||||||||||||||
|
3.
|
Site
Selection Visits
|
||||||||||||||||||||||||||||
|
Site
Visits
|
£ | 0 | $ | 0 |
Using
same sites as Doxirubicin study
|
||||||||||||||||||||||||
|
Approval
of Sites by PM
|
£ | 0 | $ | 0 |
0.5
hr PM per site
|
||||||||||||||||||||||||
|
Selection
of Central Laboratory
|
NA
|
£ | 0 | $ | 0 |
Assume
not needed
|
|||||||||||||||||||||||
|
4.
|
Regulatory
& EC Approval
|
||||||||||||||||||||||||||||
|
Regulatory
Submissions
|
4 | 16 | £ | 904 | $ | 1,718 |
8
hrs CRA per site and 4 hrs admin to collate documents
|
||||||||||||||||||||||
|
Ethics
Submissions
|
2 | 16 | £ | 852 | $ | 1,619 |
8
hrs CRA per site. 2 hrs admin per site
|
||||||||||||||||||||||
|
Obtain
Import/Export License
|
£ | 0 | $ | 0 |
Not
needed
|
||||||||||||||||||||||||
|
5.
|
Study
Preparation
|
||||||||||||||||||||||||||||
|
Monitoring
Guidelines
|
4 | £ | 264 | $ | 502 |
4
hrs for PM to modify and final
|
|||||||||||||||||||||||
|
Investigator/Hospital
Contracts
|
8 | 8 | £ | 928 | $ | 1,763 |
4
hrs per site for PM write + 4 hrs CRA per site to
negotiate/distribute
|
||||||||||||||||||||||
|
Local
Insurance
|
16 | £ | 800 | $ | 1,520 |
16
hrs to obtain
|
|||||||||||||||||||||||
|
6.
|
Sponsor
Meetings & teleconferences
|
||||||||||||||||||||||||||||
|
Bi-weekly
teleconferences with CRA, PM & research secretary
|
9 | 9 | 9 | £ | 1,278 | $ | 2,428 |
On
average 0.5 hrs bi-weekly teleconference for 9 months
|
|||||||||||||||||||||
|
Kick-off
Meeting
|
£ | 0 | $ | 0 |
Assume
not required
|
||||||||||||||||||||||||
|
7.
|
Monitor
Training
|
||||||||||||||||||||||||||||
|
CRA
training preparation
|
8 | £ | 528 | $ | 1,003 |
8
hrs (PM) to prepare presentation
|
|||||||||||||||||||||||
|
CRA
training attendance
|
6 | 6 | 6 | £ | 852 | $ | 1,619 |
6
hrs
|
|||||||||||||||||||||
|
8.
|
Investigator
Meetings
|
||||||||||||||||||||||||||||
|
Investigator
Meeting preparation
|
0 | 0 | 0 | £ | 0 | $ | 0 |
No
Investigator Meeting
|
|||||||||||||||||||||
|
Investigator
Meeting attendance
|
0 | 0 | 0 | £ | 0 | $ | 0 |
N/A
|
|||||||||||||||||||||
|
Page
1 of 6
|
CONFIDENTIAL
|
SCHEDULE
1
|
Number of Hours per task per position
|
||||||||||||||||||||||||||||
|
Task
|
Position
|
Admin
|
CRA
|
PM
|
OA Auditor
|
|||||||||||||||||||||||
|
No.
|
Hourly Rate
|
£26
|
£50
|
£66
|
£81
|
Cost (£)
|
Cost (US$)
|
Assumptions
|
||||||||||||||||||||
|
9.
|
Site
Initiation Visits
|
|||||||||||||||||||||||||||
|
Site
Visits
|
23 | £ | 1,150 | $ | 2,185 |
1
local site – 9 hrs to include 2 hrs preparation, 4 hr visit, 1 hr travel
and 2 hrs for report writing and related administration
1
provincial site – 14 hrs to include 2 hrs preparation, 4 hr visit, 6 hrs
travel and 2 hrs for report writing and related
administration
|
||||||||||||||||||||||
|
10.
|
Monitoring
|
|||||||||||||||||||||||||||
|
Routine
monitoring Visits
|
248 | £ | 12,400 | $ | 23,560 |
8
monitoring visits per site: (once every 3 weeks during recruitment and PK
sampling period: over 4 months = 6) and once every 6 weeks over the next 3
months = 2; 1 local site – 13 hrs to include 2 hrs preparation, 8 hr
visit, 1 hr travel and 2 hrs for report writing and related
administration
1
provincial site – 18 hrs to include 2 hrs preparation, 8 hr visit, 6 hrs
travel and 2 hrs for report writing and related
administration
|
||||||||||||||||||||||
|
Internal
monitoring
|
72 | £ | 3,600 | $ | 6,840 |
1 hr
per week per site for 9 months – CRF tracking and status
update
|
||||||||||||||||||||||
|
Tel.
Contacts/Correspondence
|
18 | £ | 900 | $ | 1,710 |
0.5
hr bi-weekly per site for 9 months (duration of the study)
|
||||||||||||||||||||||
|
Query
Management
|
60 | £ | 3,000 | $ | 5,700 |
Assume
8 queries per patient 0.25 hrs per query for CRA to answer
|
||||||||||||||||||||||
|
SAE
reporting to Sponsor
|
60 | £ | 3,000 | $ | 5,700 |
2
hrs per SAE (assume 1 SAE/patient)
|
||||||||||||||||||||||
|
11.
|
Medical
Safety
|
|||||||||||||||||||||||||||
|
SAE
reporting to Regulatory
|
30 | £ | 1,500 | $ | 2,850 |
Assume
1 hr per SAE
|
||||||||||||||||||||||
|
12.
|
Project
Management
|
|||||||||||||||||||||||||||
|
Set-up
& Maintenance, Project Coordination, Sponsor Contact, Project
Tracking, Investigator fee payments
|
343 | £ | 22,638 | $ | 43,012 |
12
hrs per week for the first 2 months then 8 hrs per week for the remaining
7 months
|
||||||||||||||||||||||
|
13.
|
Quality
Assurance/Audits
|
|||||||||||||||||||||||||||
| 24 | £ | 1,944 | $ | 3,694 |
Assume
1 site audit
24
hours each to include:
4
hours preparation, 8 hours return International travel, 8 hours at site
and 4 hours report writing.
|
|||||||||||||||||||||||
|
14.
|
Sponsor
Audits
|
|||||||||||||||||||||||||||
| £ | 0 |
None
assumed for now
|
||||||||||||||||||||||||||
|
15.
|
Site
Close-Out
|
|||||||||||||||||||||||||||
|
Site
Visits
|
23 | £ | 1,150 | $ | 2,185 |
Same
assumptions as initiation visits
|
||||||||||||||||||||||
|
16.
|
Study
Follow Up
|
|||||||||||||||||||||||||||
| £ | 0 | $ | 0 |
Costs
included in Close-Out Visits
|
||||||||||||||||||||||||
|
17.
|
Administration
|
|||||||||||||||||||||||||||
|
Study
File set up
|
18 | £ | 468 | $ | 889 |
3
hrs per file, 6 files (4/site, 1/country & 1 master)
|
||||||||||||||||||||||
| 46 | £ | 1,196 | $ | 2,272 |
2
hrs/week for the first 2 months, then 1 hr/week for the remaining 7
months
|
|||||||||||||||||||||||
| 6 | £ | 156 | $ | 296 |
Payments
to investigators – assume 2 payments per site. 1 hour per payment Research
Secretary and 0.5 hours per payment Finance Admin
|
|||||||||||||||||||||||
|
18.
|
PK
Sampling
|
|||||||||||||||||||||||||||
| 32 | £ | 1,600 | $ | 3,040 |
Time
for handling, tracking and shipping.
|
|||||||||||||||||||||||
|
Page
2 of 6
|
CONFIDENTIAL
|
SCHEDULE
1
|
Number of Hours per task per position
|
||||||||||||||||||||||||||||
|
Task
|
Position
|
Admin
|
CRA
|
PM
|
OA Auditor
|
|||||||||||||||||||||||
|
No.
|
Hourly Rate
|
£26
|
£50
|
£66
|
£81
|
Cost (£)
|
Cost (US$)
|
Assumptions
|
||||||||||||||||||||
|
19.
|
Data
Management: Stats and Randomisation
|
|||||||||||||||||||||||||||
| £ | 51,053 | $ | 97,000 |
To
include data management, statistical analysis and report writing (draft
& final).
|
||||||||||||||||||||||||
|
20.
|
Passthroughs
|
See
passthrough table
|
||||||||||||||||||||||||||
|
Calculation
based on £1 = $1.9
|
£ | 144,333 | $ | 217,232 | ||||||||||||||||||||||||
Subject
to exchange rate fluctuations and marked to British Pound.
|
Page
3 of 6
|
CONFIDENTIAL
|
SCHEDULE
1
Pharm-Olam
International
Pass
Through Costs
Study:
Taxotere PK YMB Study YB1002-203
Number
of Patients: 30 Randomised
Countries: Serbia (2
sites)
Date:
25th January 2005
|
Note: The below costs are estimates only
|
|||||||||
|
Item
|
Cost (£)
|
Cost ($)
|
Note
|
||||||
|
Fixed
charge for Paper, photocopying, faxes, telephone, mobile telephone, Study
Files
|
£ | 8,003 | $ | 15,206 |
To
be charged on a monthly basis based on 12 months @ £667 per
month
|
||||
|
Purchase
of Drug Taxotere
|
£ | 157,895 | $ | 300,000 |
Average
$10,000 per patient. (assumes 20pts @ 2 cycles & 10 pts @ 7
cycles)
|
||||
|
Auditor
Travel
|
£ | 684 | $ | 1,300 |
Assume
1 site audit – Approx. $1,300/audit for travel, meals and
accommodation
|
||||
|
Monitor
travel including meals (selection, initiation, monitoring and close out
visits)
|
£ | 2,321 | $ | 4,410 |
26
visits per site in total x $63 per visit = $882
Note:
This is an approximate fee. Mileage will be charged @ $0.65 per
mile.
|
||||
|
CRF
Printing
|
£ | 947 | $ | 1,800 |
40
CRF’s @ $45/CRF
|
||||
|
Regulatory
and Ethics
|
£ | 900 | $ | 1,620 |
Regs.
-£200 GBP; Provincial Site Ethics £700 GBP
|
||||
|
Local
Insurance certificates
|
£ | 5,789 | $ | 11,000 |
Approximately
$11,000 for 500,000 Euros coverage
|
||||
|
PK
specialist consultancy for Protocol finalization
|
£ | 0 |
None
|
||||||
|
Investigator
fees to include labs, etc*
|
£ | 53,263 | $ | 101,200 |
For
pts completing 2 cycles = $2,140 + $525 labs = $2,665, For Pts completing
all 7 cycles = $3,740 + $1,050 labs = $4,790 Assume 20 pts 2 cycles &
10 pts 7 cycles
|
||||
|
Bank
charges for Investigator fees payment
|
£ | 133 | $ | 240 |
Assume
$60 per payment (total of 4 payments)
|
||||
|
Total
|
£ | 229,936 | $ | 436,776 |
£1
=
$1.9
|
||||
The
following are INCLUDED in the fixed charge (based on the
net service value and to be amended if the service costs alter): Paper,
photocopying, faxes, telephone, mobile telephone, Study Files
The
following Non-Fixed
costs will be charged extra (see above table for details) and will be subject to
a 5% handling charge with an accompanying receipt; Couriers, Printing,
Teleconference, Travel (flights or per km mileage), Meals, Accommodation,
Regulatory and Ethics fees, Investigator fees)
|
Page 4
of 6
|
CONFIDENTIAL
|
SCHEDULE
1
Pharm-Olam
International
Translation
Times
Study:
Taxotere PK YMB Study YB1002-203
Number
of Patients: 30 Randomised
Countries: Serbia
(2 sites)
Date:
25th January 2005
Note:
This is an assumption and depends on the final number of pages to be
translated
|
Document
|
Assumptions
|
Number of Hours
|
||
|
Patient
information sheet
|
8
hours per country
|
|||
|
Consent
form
|
4
hours per country
|
|||
|
Drug
labels
|
NA (assume not needed)
|
NA
|
||
|
EC
aspproval letter
|
4
hours per site
|
|||
|
Import
licence and regulatory approval letter
|
8
hours per country
|
|||
|
Insurance
certificate
|
4
hours per country
|
|||
|
Hospital/Investigator
Contract
|
8
hours per site
|
|||
|
Total
|
0
|
N.B.
These translation times are an estimate, a more accurate costing can be provided
after a review of the full study documentation. If you require local language
correspondence ( e.g. to/from Regulatory Authorities, EC’s and investigators) to
be translated this will be charged at £75 per page.
|
Page 5
of 6
|
CONFIDENTIAL
|
SCHEDULE
1
Pharm-Olam
International
Timelines
Study:
Taxotere PK YMB Study YB1002-203
Number
of Patients: 30 Randomised
Countries:
Serbia (2 sites)
Date:
25th January 2005
|
Start
Date
|
December
1, 2004
|
|
|
First
patient in (FPI)
|
February
1, 2005
|
|
|
Last
patient in (LPI)
|
May
31, 2005
|
|
|
Last
patient out
|
October
30, 2005
|
|
|
Close
out
|
December
31, 2005
|
|
Page 6
of 6
|
CONFIDENTIAL
|
