CLINICAL TRIAL SERVICES AGREEMENT
This Agreement is made and entered into this 16th day
of March 2007 by and between:
HARVARD CLINICAL RESEARCH INSTITUTE, INC. ("HCRI")
000 Xxxxxxxxxxxx Xxxxxx
Xxxxxx, Xxxxxxxxxxxxx 00000
and
VICOR TECHNOLOGIES, INC. ("VICOR")
0000 XX Xxxxxxxxx Xxxxxxxxx, Xxxxx 000
Xxxx Xxxxx, XX 00000
"Prospective, Multi-Center Study Of The Ability Of The PD2i Cardiac Analyzer To
Predict Risk Of Ventricular TachyArrhythrnic Events Such As, Sudden Cardiac
Death( SCD), VentricuLar Fibrillation (VF) or Ventricular Tachycardia in High
Risk Patients"
Protocol # VTI-2003-03
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WHEREAS, VICOR desires to engage HCRI for the purpose of providing Clinical
Trial Services, as defined in Exhibit A to this Agreement, which will serve as
the Scope of Work and budget for the Agreement, for Protocol #VTI-2003-03,
entitled, Prospective, "Multi-Center Study Of The Ability Of The PD2i Cardiac
Analyzer To Predict Risk Of Ventricular TachyArrhythmic Events Such As, Sudden
Cardiac Death (SCD), Ventricular Fibrillation (VF) or Ventricular Tachycardia
(VT) in High Risk Patients," dated May 5, 2005 (incorporated herein by
reference);
WHEREAS, HCRI and its professionals have experience in the development and
administration of clinical trials of various Investigational Products; and
WHEREAS, the parties hereto deem it to be in their individual and mutual
best interest to set forth the terms and conditions of their relationship
herein; and
NOW, THEREFORE, in consideration of the mutual covenants and premises
herein contained, HCRI and VICOR agree as follows:
1. DEFINITIONS.
"Clinical Sites" shall mean the hospitals and other medical institutions
that are participating as clinical study sites and seeing patients in
accordance with the protocol.
"Clinical Trial Data" shall mean data provided in reference to this Study
by the Clinical Sites during the Trial and may include, but is not limited
to, information contained in case report forms, core laboratory data, if
any, and clinical laboratory data, if any.
"Clinical Trial Services" shall mean the Services described in Exhibit A to
this Agreement, which shall serve as the Scope of Work and budget for this
Agreement.
"Investigational Product" shall mean the device, pharmaceutical, or
biopharmaceutical product under investigation for this Trial.
"Pre-Existing Intellectual Property" means all proprietary rights,
including patents, copyrights, trade secrets and other proprietary
information relating to the Investigational Product and owned or licensed
by VICOR.
"Principal Investigators" shall mean collectively the investigator who
functions as overall principal investigator for the Trial and the
investigators who function as principal investigators at the Clinical
Sites.
"Protocol" shall mean the investigational plan developed pursuant to this
Agreement for performing the Trial.
"Trial" shall mean the clinical trial described in the Protocol.
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2. VICOR LIAISON.
VICOR shall designate a person who shall be VICOR's primary liaison (the
"Liaison") with HCRI for all purposes pursuant to this Agreement. The Liaison's
duties shall include responding promptly and fully to all reasonable requests
from HCRI. The Liaison may consult informally with HCRI's representatives, both
in person and by telephone, regarding the Trial. All notices and approvals to be
made by VICOR pursuant to this Agreement shall be made by or through the
Liaison, and HCRI shall be entitled to look solely to the Liaison for such
notices and approvals. The Liaison shall be Xx. Xxxxx Xxxxx, President, Chief
Executive and Financial Officer.
3. PRIMACY OF HEALTH CARE MISSION.
VICOR acknowledges that the primary mission of HCRI is health care,
education and the advancement of knowledge and, consequently, all Clinical Trial
Services, (described in Exhibit A), provided by HCRI under this Agreement shall
be performed in a manner best suited to carry out that mission. Furthermore,
HCRI does not guarantee specific results of the Trial.
4. DATA OWNERSHIP.
VICOR shall have ownership rights to the Clinical Trial Data, as well as to
the content of. analyses and reports relating to the Trial which are delivered
to VICOR by HCRI. VICOR shall be free to use the Clinical Trial Data and the
content of such analyses and reports for its own business purposes, provided
however that VICOR agrees that it shall be solely liable for the content of the
analyses or reports if it changes or otherwise modifies such analyses or reports
in any way at any time from the form in which they were delivered to VICOR. HCRI
shall own all rights to the procedures, methodologies, computer programs,
analytic tools, know how and work papers used and/or generated by HCRI in
conducting such analyses relating to the Trial (collectively, "HCRI Know-How").
VICOR agrees not to reproduce and/or disseminate such Know-How for its benefit
or the benefit of any third party.
5. VICOR'S OBLIGATIONS.
a. Compensation and Payment. In consideration for its services, HCRI will
receive remuneration equal to an estimated fee of $1,270,460 as detailed in
attached Exhibit A. VICOR and HCRI expressly agree that such fee represents an
estimate arrived upon in good faith and based on the parties' mutual
understanding of the Scope of Work at the outset of this Agreement. This
estimated fee will be invoiced according to the payment schedule provided in
attached Exhibit 13. VICOR agrees to pay each invoice upon receipt of the
invoice. To the extent there is no good faith dispute as to the validity of the
invoice; accounts not paid within thirty (30) days of receipt of an invoice will
be considered overdue. Overdue accounts will be charged 1.5% of the invoice
total for each month that the invoice remains unpaid.
b. Changes in Scope. Amounts paid by VICOR under this section may be
increased if the Scope of Work detailed in Exhibit A changes. If changes in
scope are required by VICOR, a Contract Change Order describing the modification
to the Scope of Work and detailing the associated adjustment to the project
costs will be issued by HCRI and agreed to in writing between HCRI and VICOR.
Additionally, VICOR acknowledges that certain adjustments to the estimated fee
may be necessary during the term of this Agreement along with a detailed
explanation of same. HCRI shall provide VICOR with prompt notice of any
adjustment deemed
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necessary. Further, the parties shall review and address any dispute relating to
all such adjustments.
c. Use of Funds. HCRI shall monitor expenditures, in accordance with its
policies, to ensure that the funds provided by VICOR are spent in accordance
with this Agreement and approved budgets. However, HCRI shall have the right to
rebudget funds between cost categories as deemed necessary by HCRI.
d. Representations Concerning the Investigational Product. VICOR represents
warrants and agrees that the Investigational Product is produced in accordance
with all applicable laws and regulations. VICOR further represents, warrants and
agrees that appropriate federal and state government authorization has been or
will be obtained for the use of the Investigational Product for the Trial.
e. Adverse Reactions. VICOR agrees that HCRI is not responsible for the
costs of diagnosis, care and treatment of any undesirable side effects, adverse
reactions, illness or injury to a participant in the Trial which result from
participation in the Trial, except to the extent such costs arise directly from
HCRI's gross negligence or reckless or intentional misconduct. This section is
not intended to create any third-party contractual benefit for any participants
in the Trial.
f. Immediate Notification of Adverse Reactions. VICOR shall immediately
transmit to HCRI any information regarding any Serious Adverse Events associated
with the use of the Investigational Product. HCRI shall immediately transmit to
VICOR and the sites, or their designees, any information regarding previously
unreported Serious Adverse Events experienced by participants in the Trial.
6. CONFIDENTIALITY; PUBLICATION.
a. VICOR Confidential Information Defined. "VICOR Confidential Information"
shall mean information provided to HCRI by VICOR pursuant to this Agreement
which is marked "Confidential" when disclosed or otherwise treated as
confidential by VICOR. If not in tangible form, VICOR agrees to identify such
information as confidential when disclosed and make reasonable efforts to
confirm in writing the confidential nature of the information within thirty (30)
days of such disclosure. Notwithstanding the foregoing, "VICOR Confidential
Information" shall not include information or materials that: (i) were in the
possession of HCRI before receipt from VICOR; (ii) were or become available to
the public through no fault of HCRI; (iii) have been received in good faith by
HCRI from a third party who does not owe a duty of confidentiality to VICOR;
(iv) have been independently developed by HCRI without any use of VICOR
Confidential Information; or (v) are required to be disclosed by law.
b. Limited Delivery of VICOR Confidential Information. The free
dissemination of information is an important policy of HCRI. To minimize
questions concerning the confidentiality of disclosures, trade secrets, or
proprietary data or information, VICOR agrees to limit to the extent possible
the delivery of VICOR Confidential Information to HCRI.
c. Publication. In accordance with this subparagraph (c), HCRI shall have
the right to publish or otherwise publicly disclose the results of the Trial and
other information gained in
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the course of this Agreement. During the term of this Agreement and for a period
of one (I) year following the termination or expiration of this Agreement, to
protect patent rights and VICOR Confidential Information, HCRI shall submit
manuscripts, abstracts and similar material generated by HCRI as a result of
this Agreement ("Publications") to VICOR via the VICOR Liaison for review and
comment thirty (30) days prior to the planned publication or disclosure date.
VICOR will advise HCRI within thirty (30) days of receiving any such
Publication of: (i) any disclosure of information that will result in a loss of
patent rights ("Patentable Material"), and (ii) any disclosure of VICOR
Confidential Information. If VICOR informs HCRI that it is desirable to file one
or more patent applications on Patentable Material disclosed in the Publication,
HCRI may, at its option: (i) delete the Patentable Material and publish or
disclose the Publication; or (ii) postpone Publication for not more than sixty
(60) days beyond the date on which the Publication was provided to VICOR to
provide time to file such patent applications. Upon mutual agreement that the
Publication contains VICOR Confidential Information, HCRI will delete such
information. Any dispute relating to the Publication shall be addressed and
resolved by the parties.
7. PUBLICITY.
No press release, advertising, promotional sales literature or other
promotional written statements or promotional oral statements to the public in
connection with or alluding to work performed under this Agreement or the
relationship between the parties created by it, having or containing any
reference to HCRI or any of its affiliates or VICOR, shall be made by either
party without the prior written approval of the other party. HCRI shall,
however, have the right to acknowledge VICOR's support of the investigations
under this Agreement in HCRI's brochure, web site, scientific publications and
other scientific communications.
8. INVENTIONS.
HCRI acknowledges VICOR's ownership interest in all Pre-Existing
Intellectual Property in the Investigational Product. HCRI agrees to take no
action inconsistent with VICOR's ownership of such Pre-Existing Intellectual
Property.
During the course of the Trial, should any new inventions, developments or
improvements (whether patentable or not) be conceived and reduced to practice by
HCRI or VICOR, the parties agree that ownership shall be determined by
inventorship in accordance with U.S. Patent Laws. The parties further agree to
provide each other with prompt notice of any such new invention, development or
improvement in order for the parties to address related issues, including but
not limited to, the preparation and filing of one or more patent applications
and negotiation of cross-licensing opportunities which may be mutually
desirable.
Notwithstanding the foregoing, the parties agree that nothing in this
Agreement by implication or otherwise shall constitute a grant of rights to any
Pre-Existing Intellectual Property or to any new invention, development or
improvement owned or developed by either party during or after the Trial.
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9. INDEMNIFICATION.
a. Vicor shall indemnify, defend and hold harmless HCRI and its trustees,
officers, medical and professional staff, employees, agents, subcontractors, and
their respective successors, heirs and assigns ("HCRI Indemnities"), against any
liability, damage, loss, or expense (including reasonable attorneys' fees and
expenses of litigation) incurred by or imposed upon the HCRI Indemnities or any
one of them in connection with any claims, suits, actions, demands or judgments:
(i) arising out of any theory of product liability (including, but not limited
to, actions in the form of tort, warranty, or strict liability) resulting from
the Protocol; (ii) arising out of any side effect or adverse reaction, illness
or injury resulting from the Protocol or the Indemnities' performance under this
Agreement and occurring to any person involved in the Trial; or (iii) arising
out of damage to any property resulting from and occurring during the
Indemnities' performance of this Agreement.
b. HCRI shall indemnify, defend and hold harmless Vicor and its trustees,
officers, medical and professional staff, employees, agents, subcontractors and
their respective successors, heirs and assigns ("Vicor Indemnities"), against
any liability, damage, loss, or expense (including reasonable attorneys' fees
and expenses of litigation) incurred by or imposed upon the Vicor Indemnities or
any one of them in connection with any claims, suits, actions, demands or
judgments arising out of or caused by: (i) the falsity of any representation or
the breach of any warranty made by HCRI in this Agreement; (ii) HCRI's default
under any term or provision hereof on its part to be observed and performed; or
(iii) the negligent activities, or reckless or intentional misconduct of HCRI,
its trustees, officers, medical and professional staff, employees, agents or
subcontractors. Notwithstanding the foregoing, HCRI's total liability for
indemnification hereunder shall not exceed one (I) times the compensation
received by HCRI under this Agreement.
c. Either party's indemnification under 9(a) (b) shall not apply to the
extent that any liability, damage, loss or expense is directly attributable to
the grossly negligent activities, or reckless or intentional misconduct of the
Indemnities.
d. Both parties agree, at its own expense, to provide attorneys reasonably
acceptable to the Indemnitee to defend against any actions brought or filed
against any party indemnified hereunder with respect to the subject of indemnity
contained herein, whether or not such actions are rightfully brought.
e. Both parties agree to provide each other with prompt written notice of
any claim, suit, action, demand or judgment as described in Section 9(a) of
which it has actual knowledge or a reasonable belief thereof.
f. This Section 9 shall survive expiration or termination of this
Agreement.
10. INSURANCE.
a. VICOR shall, at its sole cost and expense, procure and maintain
comprehensive general liability insurance in amounts not less than $2,000,000
per incident and $2,000,000 annual aggregate and naming the Index-al-lams as
additional insured. Such comprehensive general liability insurance shall provide
(i) product liability coverage and (ii) broad form contractual liability
coverage for VICOR's indemnification under the preceding section. If
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VICOR elects to self-insure all or part of the limits described above (including
deductibles or retentions which are in excess of $250,000 annual aggregate) such
self-insurance program must be acceptable to HCRI and HCRI's insurance carrier.
The minimum amounts of insurance coverage required under this section shall not
be construed to create a limit of VICOR's liability with respect to its
indemnification under the preceding section of this Agreement.
b. VICOR shall provide HCRI with written evidence of such insurance upon
request of HCRI. VICOR shall provide HCRI with written notice at least fifteen
(15) days prior to the cancellation, non-renewal or material change in such
insurance.
c. VICOR shall maintain such comprehensive general liability insurance (i)
during the continuance of the Trial or the term of this Agreement, whichever is
longer, and (ii) for a reasonable period after the period referred to in (c)(i)
above which in no event shall be less than six (6) years.
d. This Section 10 shall survive expiration or termination of this
Agreement.
11. LIMITATION OF LIABILITY AND REMEDIES.
a. IN THE EVENT OF ANY MA'T'ERIAL BREACH, OMISSION, OR NEGLIGENCE BY HCRI
IN THE PERFORMANCE OF ITS OBLIGATIONS UNDER THIS AGREEMENT, VICOR AGREES THAT
ITS FIRST RECOURSE SHALL BE TO SEEK REPERFORMANCE, BY HCRI, OF THE SERVICES
DETRIMENTALLY IMPACTED BY SUCH ERROR OR OMISSION AT THE SOLE COST AND EXPENSE OF
HCRI. IN NO EVENT SHALL HCRI'S LIABILITY FOR SUCH MATERIAL BREACH OR OMISSION
EXCEED THE FEES PAID TO HCRI FOR THE AFFECTED SERVICE. VICOR FURTHER AGREES THAT
HCRI SHALL NOT BE LIABLE TO VICOR FOR ANY SPECIAL, INDIRECT, EXEMPLARY,
INCIDENTAL OR CONSEQUENTIAL DAMAGES INCLUDING BUT NOT LIMITED TO ANY DAMAGES
RESULTING FROM LOSS OF DATA, DELAY IN- THE STUDY, LOSS OF PROFITS OR LOSS OF
BUSINESS ARISING OUT OF OR IN CONNECTION WITH THIS AGREEMENT OR ANY PRODUCTS,
SERVICES OR MATERIALS FURNISHED HEREUNDER, EVEN IF HCRI HAS BEEN ADVISED OR
SHOULD KNOW OF THE POSSIBILITY OF SUCH DAMAGES.
b. EXCEPT AS EXPRESSLY STATED TO THE CONTRARY, THE LIMITATIONS STATED IN
SECTION 11 (a) SHALL APPLY WHETHER THE ASSEKLED CLAIM, LIABILITY OR DAMAGES ARE
BASED ON CONTRACT (INCLUDING BUT NOT LIMITED TO BREACH OF WARRANTY), TORT
(INCLUDING BUT NOT LIMITED TO NEGLIGENCE AND STRICT LIABILITY) OR ANY OTHER
LEGAL OR EQUITABLE GROUNDS, AND REGARDLESS OF WHETHER THE ASSERTED CLAIM,
LIABILITY OR DAMAGES ARISE FROM PERSONAL INJURY, PROPERTY DAMAGE, ECONOMIC LOSS
OR ANY OTHER KIND OF INJURY, LOSS OR DAMAGE. EACH OF SUCH LIMITATIONS IS
INTENDED TO BE ENFORCEABLE REGARDLESS OF WHETHER ANY OTHER EXCLUSIVE OR
NONEXCLUSIVE REMEDY UNDER THIS AGREEMENT FAILS OF ITS ESSENTIAL PURPOSE.
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c. VICOR acknowledges that the fees described in Exhibit A and the other
economic terms of this Agreement and its Exhibits reflect the allocation of
risks and the limitations of HCRI' s liability hereunder.
12. TERM; TERMINATION.
a. Term. This Agreement shall continue in full force and effect until VICOR
has provided final payment to HCRI. Termination of this Agreement, however,
shall not relieve the obligations undertaken by the parties in Sections 6, 7, 8,
9, 10, and 11.
b. Termination without Cause. Either party may terminate this Agreement
without cause by providing sixty (60) days written notice to the other party.
c. Termination for Bankruptcy/Insolvency. Either party may immediately
terminate this Agreement if the other party files a petition in bankruptcy or is
adjudicated as bankrupt or insolvent, or makes an assignment for the benefit of
creditors, or an arrangement pursuant to any bankruptcy law, or if the other
party discontinues its business or if a receiver is appointed for the other
party or the other party's business who is not discharged within thirty (30)
days.
d. Termination for Cause. Either party may terminate this Agreement for
cause after providing the breaching party with thirty (30) days written notice
of the breach and the opportunity to cure the breach during such period.
e. Effect of Termination. Upon termination of this Agreement for any
reason, VICOR shall promptly pay HCRI on a time and materials basis for all work
performed and expenses incurred through the effective date of termination
including, without limitation, amounts due for closeout costs and non-cancelable
commitments incurred through that date, if such costs exceed the amounts
previously paid under this Agreement. Upon termination or expiration of this
Agreement, HCRI shall retain title to all equipment purchased or fabricated by
it with funds provided by VICOR under this Agreement.
13. COMPLIANCE WITH LAWS AND POLICIES.
a. Compliance with Law. VICOR and HCRI shall comply with all applicable
federal, state and local laws, regulations and guidelines, including but not
limited to any such laws, regulations or guidelines concerning human subject
research.
b. Adherence to Policies. VICOR recognizes that in performing services
under this Agreement, HCRI is bound by and all rights of VICOR will be subject
to the Faculty of Medicine of Harvard University's Faculty Policies on Integrity
in Science.
c. Financial Disclosure. Pursuant to any applicable federal, state and
local laws, regulations or guidelines, VICOR, Clinical Sites, Principal
Investigators and any employees under the supervision of Principal Investigator
who are directly involved in this Study ("Parties of Interest") may be required
to complete and sign a financial conflicts of interests disclosure form(s). Such
forms must disclose any financial interests and/or investments in VICOR held by
Parties of Interest. VICOR agrees that it shall retain primary responsibility
for reporting all financial interests of Parties of Interest in accordance with
any and all applicable regulations,
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statutes or guidelines and HCRI shall be responsible for obtaining any required
forms from the Clinical Sites. In compliance with any applicable regulatory
requirement Parties of Interest shall promptly update forms, as needed to
maintain their accuracy and completeness during the Study and for one year after
its completion.
14. NON-SOLICITATION; FINANCIAL INTEREST IN VICOR.
a. VICOR shall not solicit for employment or employ, at any time during the
term hereof or for a period of one (1) year thereafter, any person employed by
HCRI at any time during the term hereof, without the prior written consent of
HCRI. If VICOR employs a staff member of HCRI without HCRI's prior written
consent, VICOR agrees to pay a fee of 100% of the individual's salary or
expected compensation for the first year of service.
b. Neither VICOR nor any affiliate or subsidiary of VICOR shall grant,
issue or provide or agree to grant, issue or provide any financial interest,
including any consulting or other fee or stock or other equity, to any person
employed by HCRI or any immediate family member of any person employed by HCRI
without the prior written consent of the President and Chief Executive Officer
of HCRI.
15. ARBITRATION.
a. The parties shall settle by arbitration any controversy or claim between
them arising directly or indirectly under this Agreement, whether based on
contract, tort, fraud, misrepresentation or other legal theory, and whether or
not arbitration has been expressly referenced elsewhere in a particular section
or a particular subsection of this Agreement. The arbitration shall occur in
Boston, Massachusetts under the then current rules and supervision of the
American Arbitration Association. If the dispute involves a claim for money in
the amount of $500,000 or less and does not involve any claims relating to
ownership, use, or disclosure of intellectual property, the arbitration shall be
before a single arbitrator whom the parties shall select from a panel of persons
knowledgeable in the therapeutic area addressed by the Trial and clinical
research; otherwise, the arbitration shall be before three arbitrators, one
selected by VICOR, one selected by HCRI, and the third selected by the two
arbitrators so selected. The arbitrator or arbitrators shall not have the power
to award punitive or exemplary damages. The decision. and award of the
arbitrator or arbitrators shall be final and binding and the award rendered may
be entered in any court having competent jurisdiction. The parties shall each
pay their own attorneys' fees associated with the arbitration, and shall pay the
other costs and expenses of the arbitration as the rules of the American
Arbitration Association or the arbitrator provide.
b. Any party may request arbitration to resolve any controversy or claim,
between them, as provided above, by written notice to the other proposing an
arbitrator. The other party receiving such written notice shall have thirty (30)
days in which to agree with such choice of arbitrator or, if three arbitrators
are required, to propose its arbitrator.
16. FORCE MAJEURE.
a. Neither party shall be liable for any unforeseeable event beyond its
reasonable control not caused by the fault or negligence of such party, which
causes such party to be unable
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to perform its obligations under this Agreement, and which it has been unable to
overcome by the exercise of due diligence.
b. In the event of the occurrence of such a force majeure event, the party
unable to perform shall promptly notify the other party. It shall further use
its best efforts to resume performance as quickly as possible and shall suspend
performance only for such period of time as is necessary as a result of the
force majeure event.
17. MISCELLANEOUS.
This Agreement constitutes the entire agreement among the parties, and all
prior negotiations, representations, agreements and understandings are
superseded hereby. No agreements amending, altering or supplementing the terms
hereof may be made except by means of a written document signed by the duly
authorized representatives of the parties. Any notice required by this Agreement
shall be given by prepaid, first class, certified mail, return receipt
requested, to the parties at their addresses set forth above. This Agreement
shall be governed by and construed in accordance with the laws of The
Commonwealth of Massachusetts. The invalidity or unenforceability of any term or
provision hereof shall not affect the validity or enforceability of any other
term or provision hereof. Failure of either party to enforce a right under this
Agreement shall not constitute a waiver of that right or the ability to later
assert that right. The headings in this Agreement are for convenience of
reference only and shall not alter or otherwise affect the meaning hereof. This
Agreement shall be binding upon and inure to the benefit of each of the parties
hereto and their successors and permitted assigns; provided, however, this
Agreement may not be assigned by either party without the prior written approval
of the other party. For the purposes of this Agreement, the parties shall be
deemed to be independent contractors and not employees or agents of the other.
IN WITNESS WHEREOF, the parties have caused this Agreement to be executed
by their duly authorized representatives.
VICOR TECHNOLOGIES INC. HARVARD CLINICAL RESEARCH INSTITUTE, INC.
By: By:
---------------------------------- --------------------------------------
Name Name:
--------------------------------- ------------------------------------
Title: Title:
------------------------------ -----------------------------------
Date: Date:
------------------------------- ------------------------------------
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EXHIBIT A
SCOPE OF WORK AND BUDGET
------------------------
"Prospective, Multi-Center Study Of The Ability Of The PD2i Cardiac Analyzer
To Predict Risk Of Ventricular TachyArrhythmic Events Such As, Sudden
Cardiac Death( SCD), VentricuLar Fibrillation (VF) or Ventricular Tachycardia
in High Risk Patients"
Protocol # VTI-2003-03
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VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
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PROJECT PARAMETERS:
================================================================================
Number of Patients Enrolled: 900
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Number of Sites 30
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Enrollment Period (Approximately):: 12 months
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Enrollment Rate: 3 patients/site/month
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Follow-u. Period/Patient: 12 months
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Follow Ups: 6M, 12M
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Project Period: 30 months
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Estimated Number of Statistical Tables, 25 tables, 8 figures, 2 listings
Listings, and Figures to be Prepared by
HCRI for the Final Statistical Anal sis:
--------------------------------------------------------------------------------
Outside Vendors: Target Health
--------------------------------------------------------------------------------
Estimated Number of DSMB Meetings: 3
--------------------------------------------------------------------------------
Total Number of DSMB reports: 2
--------------------------------------------------------------------------------
Total Number of Endpoint Reports: 2 (1 6M second, 1 12M primary)
--------------------------------------------------------------------------------
Total Number of Annual Safety Reports: 2
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Estimated CEC Event Rate: 30%
--------------------------------------------------------------------------------
Estimated Number of Events to be Adjudicated: 270
================================================================================
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TASK MATRIX:
-------------------------------------------------------------------------------------------------------------------------
VICOR HCRI MFH TARGET
-------------------------------------------------------------------------------------------------------------------------
CLINICAL DOCUMENT DEVELOPMENT
-------------------------------------------------------------------------------------------------------------------------
Protocol
-------------------------------------------------------------------------------------------------------------------------
Perform literature review Yes
-------------------------------------------------------------------------------------------------------------------------
Develop statistical plan (including sample size) Yes
-------------------------------------------------------------------------------------------------------------------------
Develop protocol summary Yes
-------------------------------------------------------------------------------------------------------------------------
Develop full protocol Yes Input
-------------------------------------------------------------------------------------------------------------------------
Protocol submission to FDA o Yes Yes
-------------------------------------------------------------------------------------------------------------------------
Create TOC for Manual of Operations Yes Input
-------------------------------------------------------------------------------------------------------------------------
Distribute protocol to sites (for IRB/Ethics submission)) Yes
-------------------------------------------------------------------------------------------------------------------------
Draft Protocol amendments Yes
-------------------------------------------------------------------------------------------------------------------------
Provide notice of protocol amendments Yes
-------------------------------------------------------------------------------------------------------------------------
Distribute revised protocol to sites Yes
-------------------------------------------------------------------------------------------------------------------------
Train sites on protocol/ECG/ICD log collection Yes Yes
-------------------------------------------------------------------------------------------------------------------------
Train sites on data collection Yes
-------------------------------------------------------------------------------------------------------------------------
Train sites on protocol and protocol revisions Yes Yes
-------------------------------------------------------------------------------------------------------------------------
Case Report Forms (eCRFs)
-------------------------------------------------------------------------------------------------------------------------
Develop eCRFs Yes Yes
-------------------------------------------------------------------------------------------------------------------------
Format eCRFs Yes
-------------------------------------------------------------------------------------------------------------------------
Develop eCRF Completion Guidelines, EDC manual Yes Review
-------------------------------------------------------------------------------------------------------------------------
eCRF Changes (post final approval by sponsor) Input Yes
-------------------------------------------------------------------------------------------------------------------------
Informed Consent Form (ICF) Yes
-------------------------------------------------------------------------------------------------------------------------
Develop other study reference materials (pocket cards) Yes
-------------------------------------------------------------------------------------------------------------------------
REGULATORY STRATEGY CONSULTING
-------------------------------------------------------------------------------------------------------------------------
FDA meetings I conference calls Yes Yes Yes
-------------------------------------------------------------------------------------------------------------------------
Attend meeting
-------------------------------------------------------------------------------------------------------------------------
FDA Meeting
-------------------------------------------------------------------------------------------------------------------------
Prepare materials for meetings Yes Yes Yes
-------------------------------------------------------------------------------------------------------------------------
Prepare responses to FDA letters Yes Yes Yes
-------------------------------------------------------------------------------------------------------------------------
STUDY MANAGEMENT AND MAINTENANCE
-------------------------------------------------------------------------------------------------------------------------
Site / Investigator identification in collaboration with Sponsor Yes
-------------------------------------------------------------------------------------------------------------------------
Investigator meeting attendees:
-------------------------------------------------------------------------------------------------------------------------
Project Manager Yes
-------------------------------------------------------------------------------------------------------------------------
Inhouse Clinical Research Associate Yes
-------------------------------------------------------------------------------------------------------------------------
Clinical Site Management Coordinator Yes
-------------------------------------------------------------------------------------------------------------------------
Data Manager Yes
-------------------------------------------------------------------------------------------------------------------------
Representative from ECG Core Lab Yes
-------------------------------------------------------------------------------------------------------------------------
Site Monitors Yes
-------------------------------------------------------------------------------------------------------------------------
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007 2
Harvard Clinical Research Institute, Inc. o VICOR Technologies, Inc.
--------------------------------------------------------------------------------
-------------------------------------------------------------------------------------------------------------------------
Clinical Reviewer Yes
-------------------------------------------------------------------------------------------------------------------------
Participate in conference calls (weekly) Yes Yes Yes Yes
-------------------------------------------------------------------------------------------------------------------------
Coordinate core labs, external vendors, etc. (as applicable) Yes Yes
-------------------------------------------------------------------------------------------------------------------------
Work with selected core labs, external vendors, etc. (as applicable Yes Yes Yes
-------------------------------------------------------------------------------------------------------------------------
Develop study timelines Yes Yes Yes Yes
-------------------------------------------------------------------------------------------------------------------------
-------------------------------------------------------------------------------------------------------------------------
VICOR HCRI MFH TARGET
-------------------------------------------------------------------------------------------------------------------------
SITE MANAGEMENT
-------------------------------------------------------------------------------------------------------------------------
Distribute confidentiality agreements (CDAs) to potential sites after
approval from Vicor Yes
-------------------------------------------------------------------------------------------------------------------------
Track receipt of confidentiality agreements from potential sites Yes
-------------------------------------------------------------------------------------------------------------------------
Screen potential investigators: Develop eligibility questionnaires, track Yes
sending/receipt of questionnaires
-------------------------------------------------------------------------------------------------------------------------
Collect all regulatory documents (for example CVs, Statement of Investigator,
IRB approval, 1RBNicor approved consent form, financial Yes disclosure, etc.)
following FDA, GCP, and local requirements
-------------------------------------------------------------------------------------------------------------------------
Assist sites with informed consent modifications Yes
-------------------------------------------------------------------------------------------------------------------------
Provide weekly status tracking report of document collection Yes
-------------------------------------------------------------------------------------------------------------------------
Approve sites' complete regulatory packets for device shipment Yes
-------------------------------------------------------------------------------------------------------------------------
Submit package containing originals of each site's regulatory documents to Yes
sponsor
-------------------------------------------------------------------------------------------------------------------------
Distribute regulatory documents binder to each site Yes
-------------------------------------------------------------------------------------------------------------------------
Shipping of all study materials including core lab instructions/manuals Yes
-------------------------------------------------------------------------------------------------------------------------
Negotiate contract terms, language, and payment schedule with sites Yes
-------------------------------------------------------------------------------------------------------------------------
Track status of contracts Yes
-------------------------------------------------------------------------------------------------------------------------
Approve final contracts with sites Yes Yes
-------------------------------------------------------------------------------------------------------------------------
Negotiate and finalize letters of indemnification with sites (if required Yes Yes
by sites
-------------------------------------------------------------------------------------------------------------------------
Develop/finalize Monitoring Plan Yes Input
-------------------------------------------------------------------------------------------------------------------------
Develop/finalize Data Flow Plan/Regulations Document/Project Plan Yes
-------------------------------------------------------------------------------------------------------------------------
Develop Communications Plan Yes Yes Input Yes
-------------------------------------------------------------------------------------------------------------------------
Develop/finalize AE reporting Plan Yes
-------------------------------------------------------------------------------------------------------------------------
Conduct communication with sites to ensure enrollment targets are met,
document collection and source documents for event adjudication is Yes Yes
completed.
-------------------------------------------------------------------------------------------------------------------------
Issue investigator payments to all sites Yes
-------------------------------------------------------------------------------------------------------------------------
Provide quarterly investigator payment accounting to Vicor. Yes
-------------------------------------------------------------------------------------------------------------------------
Create and maintain a running list of FAQs for the stud Yes Input Yes
-------------------------------------------------------------------------------------------------------------------------
Manage AE reporting from site to the CEC Yes Yes
-------------------------------------------------------------------------------------------------------------------------
Re-supply study materials to sites Yes
-------------------------------------------------------------------------------------------------------------------------
INVESTIGATORS MEETING
-------------------------------------------------------------------------------------------------------------------------
Plan, organize, manage, and facilitate meeting Input Yes Input
-------------------------------------------------------------------------------------------------------------------------
Prepare agenda and distribute meeting materials Input Yes Input
-------------------------------------------------------------------------------------------------------------------------
Collect and prepare speakers' slides Input Yes Input
-------------------------------------------------------------------------------------------------------------------------
Prepare meeting minutes and distribute to attendees Yes
-------------------------------------------------------------------------------------------------------------------------
Present science/protocol/safety profile Input Yes Input
-------------------------------------------------------------------------------------------------------------------------
Present overview of device, i.e., Instructions for Use Yes
-------------------------------------------------------------------------------------------------------------------------
Present AE reporting flow Yes
-------------------------------------------------------------------------------------------------------------------------
EDC, eCRF, overview Yes
-------------------------------------------------------------------------------------------------------------------------
ECG Core Lab information/training Yes
--------------------------------------------------------------------------------------------------------------------------
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007 3
Harvard Clinical Research Institute, Inc. o VICOR Technologies, Inc.
--------------------------------------------------------------------------------
-------------------------------------------------------------------------------------------------------------------------
VICOR HCRI MFH TARGET
-------------------------------------------------------------------------------------------------------------------------
SITE MONITORING ACTIVITIES
--------------------------------------------------------------------------------------------------------------------------
Provide training for CRAs to conduct qualification/ initiation visits Yes Yes EDC Input
--------------------------------------------------------------------------------------------------------------------------
Conduct qualification/initiation visits Yes
--------------------------------------------------------------------------------------------------------------------------
Provide written qualification/initiation report Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Conduct interim on-site monitoring visits Yes
--------------------------------------------------------------------------------------------------------------------------
Review and verification of source documentation to the eCRFs Yes
--------------------------------------------------------------------------------------------------------------------------
Provide written interim visit report Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Verify Investigator's compliance with protocol and regulatory Yes Yes
requirements as part of monitoring visits
--------------------------------------------------------------------------------------------------------------------------
Obtain corrections to eCRF/Query resolution Yes Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Maintain site training of personnel Yes Yes EDC Input
--------------------------------------------------------------------------------------------------------------------------
Conduct close-out visits Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Perform post study device accountability Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Provide written-close-out reports Yes Yes
--------------------------------------------------------------------------------------------------------------------------
As
As necessary
Maintain regular contact with sites necessary Yes Yes for DM
issues
--------------------------------------------------------------------------------------------------------------------------
Coordinate investigational product distribution Yes
--------------------------------------------------------------------------------------------------------------------------
DATA MANAGEMENT ACTIVITIES (PLEASE REFER TO TARGET HEALTH INC. PROPOSAL Yes
DATED 12/29/04 FOR CLARIFICATION OF TASKS, TO INCLUDE ELECTRONIC
SIGNATURES AND ONLINE/OFFLINE EDIT CHECKS)
--------------------------------------------------------------------------------------------------------------------------
CLINICAL / SAFETY EVENT MANAGEMENT
--------------------------------------------------------------------------------------------------------------------------
Clinical adjudication management Yes
--------------------------------------------------------------------------------------------------------------------------
Identification of Endpoint events (w/Core Lab) Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Provide complete Event Packets to HCRI ( Involve ECG Core Lab) Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Track Event Packets using tracker database Yes
--------------------------------------------------------------------------------------------------------------------------
Clinical reviewer event coding & summary preparation Yes
--------------------------------------------------------------------------------------------------------------------------
Develop CEC manual of operations Yes
--------------------------------------------------------------------------------------------------------------------------
Clinical review internal adjudication of selected endpoints Yes
--------------------------------------------------------------------------------------------------------------------------
Produce report quality narratives Yes
--------------------------------------------------------------------------------------------------------------------------
Produce & distribute CEC minutes Yes
--------------------------------------------------------------------------------------------------------------------------
Clinical Event Committee (CEC) meeting coordination Yes
--------------------------------------------------------------------------------------------------------------------------
Program and validate event database Yes
--------------------------------------------------------------------------------------------------------------------------
Clinical event database management, including cleaning Yes
--------------------------------------------------------------------------------------------------------------------------
Code adverse events Yes
--------------------------------------------------------------------------------------------------------------------------
Code concomitant medications Yes
--------------------------------------------------------------------------------------------------------------------------
Safety reconciliation Yes
--------------------------------------------------------------------------------------------------------------------------
Notification of SAE's to responsible party Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Submission of SAE's to regulatory authorities Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Medical monitoring (Xx. Xxxxx) Yes
--------------------------------------------------------------------------------------------------------------------------
STATISTICS AND DATA HANDLING / ANALYSIS
--------------------------------------------------------------------------------------------------------------------------
Biostatistician input into clinical trial protocol Yes
--------------------------------------------------------------------------------------------------------------------------
Data transfers, annotated casebooks as part of EDC systems to HCRI Yes
--------------------------------------------------------------------------------------------------------------------------
Statistical Analysis Plan (SAP) and definition of data listings Yes
--------------------------------------------------------------------------------------------------------------------------
Program statistical tables, listings, and figures Yes
--------------------------------------------------------------------------------------------------------------------------
Provide data listings Yes
--------------------------------------------------------------------------------------------------------------------------
Perform analyses Yes
--------------------------------------------------------------------------------------------------------------------------
Provide format for report Yes Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Provide template report tables Yes Input/ICH
Report
--------------------------------------------------------------------------------------------------------------------------
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007 4
Harvard Clinical Research Institute, Inc. o VICOR Technologies, Inc.
--------------------------------------------------------------------------------
-------------------------------------------------------------------------------------------------------------------------
VICOR HCRI MFH TARGET
-------------------------------------------------------------------------------------------------------------------------
Review report tables Yes
--------------------------------------------------------------------------------------------------------------------------
Provide ICH compliant report (I Final) Input Yes
--------------------------------------------------------------------------------------------------------------------------
Coordinate data requests, including listings and meeting presentations. Yes Yes
(Not included in budget, will be billed as an out of scope.)
--------------------------------------------------------------------------------------------------------------------------
REPORTS
--------------------------------------------------------------------------------------------------------------------------
Study reports
--------------------------------------------------------------------------------------------------------------------------
Weekly (or as needed) study reports to sponsor/sites Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Endpoint Clinical Summary Report (1 @ 6M) Yes Yes
--------------------------------------------------------------------------------------------------------------------------
Final Clinical Summary Report (1 at 12M) Yes Yes
--------------------------------------------------------------------------------------------------------------------------
DSMB
--------------------------------------------------------------------------------------------------------------------------
Develop DSMB Charter Yes
--------------------------------------------------------------------------------------------------------------------------
Obtain DSMB member agreement to participate Yes
--------------------------------------------------------------------------------------------------------------------------
Obtain DSMB member confidentiality agreement Yes
--------------------------------------------------------------------------------------------------------------------------
Coordinate DSMB meetings Yes
--------------------------------------------------------------------------------------------------------------------------
Provide study update information to DSMB as needed Yes
--------------------------------------------------------------------------------------------------------------------------
ARCHIVING
--------------------------------------------------------------------------------------------------------------------------
Organize and index all necessary study-related documents to be archived Yes
--------------------------------------------------------------------------------------------------------------------------
Arrange archiving of the study-related documents Yes
--------------------------------------------------------------------------------------------------------------------------
Box and transfer documents to archive Yes
--------------------------------------------------------------------------------------------------------------------------
ECG/ICD CORE LAB
--------------------------------------------------------------------------------------------------------------------------
Evaluate study ECGs/ICD labels Yes
--------------------------------------------------------------------------------------------------------------------------
Data entry of PD2i Scores Yes
--------------------------------------------------------------------------------------------------------------------------
Quality Control of PD2i Scores Yes
--------------------------------------------------------------------------------------------------------------------------
Develop ECG/ICD MOP, ECG/ICD labels Yes
--------------------------------------------------------------------------------------------------------------------------
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007 5
Harvard Clinical Research Institute, Inc. o VICOR Technologies, Inc.
--------------------------------------------------------------------------------
ESTIMATED BUDGET:
================================================================================
TRIAL DESIGN & DEVELOPMENT
--------------------------------------------------------------------------------
Protocol Development $28,000
--------------------------------------------------------------------------------
SUBTOTAL $28,000
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
CLINICAL TRIAL MANAGEMENT $21,000
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
PROJECT MANAGEMENT
--------------------------------------------------------------------------------
Project Oversight $166,200
--------------------------------------------------------------------------------
Internal/External Conferencing $26,800
--------------------------------------------------------------------------------
SUBTOTAL $193,000
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
DATA MANAGEMENT
--------------------------------------------------------------------------------
Database Programming $5,400
--------------------------------------------------------------------------------
Database Maintenance $3,510
--------------------------------------------------------------------------------
Data Receipt & Tracking $4,480
--------------------------------------------------------------------------------
Data Maintenance & Administration $10,800
--------------------------------------------------------------------------------
SUBTOTAL $24,190
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
STATISTICAL ANALYSIS & REPORTING
--------------------------------------------------------------------------------
Statistical Analysis Plan $15,000
--------------------------------------------------------------------------------
Primary Endpoint $80,520
--------------------------------------------------------------------------------
Secondary Endpoint $48,120
--------------------------------------------------------------------------------
Annual Safety $32,240
--------------------------------------------------------------------------------
DSMB $35,490
--------------------------------------------------------------------------------
Final
--------------------------------------------------------------------------------
SUBTOTAL $211,370
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
CEC SERVICES $136,400
--------------------------------------------------------------------------------
SITE MANAGEMENT SERVICES $656,500
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
ESTIMATED TOTAL COSTS $1,270,460
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
ESTIMATED PASS-THROUGH COSTS
--------------------------------------------------------------------------------
Estimated ECG Costs $243,250
--------------------------------------------------------------------------------
Estimated Site Payment Costs $1,560,000
--------------------------------------------------------------------------------
Estimated Monitoring Costs $782,371
--------------------------------------------------------------------------------
Estimated CEC Participant Costs $94,500
--------------------------------------------------------------------------------
Estimated DSMB Participant Costs $12,000
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
TOTAL ESTIMATED PASS-THROUGH COSTS $2,692,121
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
ESTIMATED GRAND TOTAL $3,962,581
================================================================================
Note: The amounts presented above are total estimated costs for clinical trial
services, site payments and monitoring costs provided by HCRI and for estimated
CEC meeting and Core Laboratory costs. VICOR will pay HCRI for CEC meeting and
Core Laboratory fees based on the actual number of events brought to the CEC and
DSMB for adjudication and the actual number of TCDs and ECGs read, respectively.
Costs such as printing and shipping of CRFs and related materials, travel
expenses, overnight shipping, and other expenses incurred in connection with the
trial are not included and will be invoiced to VICOR as a pass-through expense.
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007 6
Harvard Clinical Research Institute, Inc. o VICOR Technologies, Inc.
--------------------------------------------------------------------------------
================================================================================
COST DETAIL: SITE MONITORING
--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
COST SUMMARY
--------------------------------------------------------------------------------
Lead CRA (HCRI) $10,000
--------------------------------------------------------------------------------
Total Start up Cost (1 visit/ site) (30 visits total) $15,840
--------------------------------------------------------------------------------
Total Qualification (1 visit/ site) (25 visits total) $49,500
Visits
--------------------------------------------------------------------------------
Total Site Initiation (1 visit/ site) (25 visits total) $49,500
Visits
--------------------------------------------------------------------------------
Total Cost Interim Site (6 visits/ site) (150 visits total) $376,200
Visits
--------------------------------------------------------------------------------
Total Administration $221,931
Costs
--------------------------------------------------------------------------------
Total Cost Close-out (1 visit/ site) (30 visits total) $59,400
Visits
--------------------------------------------------------------------------------
TOTAL COSTS $782,371
================================================================================
BUDGET COMPANION:
TRIAL DESIGN & DEVELOPMENT
PROTOCOL
HCRI's Trial Design and Development and Biostatistics Departments will work
closely with Vicor to develop a protocol which meets the scientific and clinical
needs of the study, which includes the selection of appropriate study endpoints,
development of the trial design and statistical rationale, inclusion and
exclusion criteria, and data collection guidelines. Protocol drafts are reviewed
by all operating departments at HCRI, as well as clinical experts from the
therapeutic area being studied. The review process is conducted to confirm not
only the completeness of the scientific and clinical justifications, but also
the clearness of detail for site compliance and conformity with both US and
outside of the US regulatory guidelines. HCRI staff has written over 100
protocols which have been used in the US, Canada, Europe, South America, New
Zealand and Australia.
INFORMED CONSENT
HCRI's Trial Design and Development and Site Management groups will draft a
template informed consent in English to be used by each site for submission to
its Institutional Review Board (IRB) or Ethics Committee. The informed consent
will meet the ICH Guidelines for Good Clinical Practice (May 1997) and Good
Clinical Practice Standards as referred to in the 21 CFR, and incorporate
relevant items described in the Helsinki Doctrine and the Belmont Report. HCRI
will work with Vicor to ensure that the document incorporates language which
will meet their corporate needs as well.
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007 7
Harvard Clinical Research Institute, Inc. o VICOR Technologies, Inc.
--------------------------------------------------------------------------------
PROJECT MANAGEMENT
A Project Manager will lead the HCRI team in completing the scope of work
for this project. The PM will provide project oversight of all study-related
activities on behalf of Vicor. The PM will facilitate communication among all
team members and serve as the Sponsor's point of contact for all study-related
activities. The Project Manager will manage the study timelines, budgets and
milestones. In addition, the Project Manager will provide review of study
deliverables, including the eCRFs, eCRF completion guidelines, and reports.
PROJECT COMMUNICATION
HCRI's project team will meet weekly to review all current matters relating
to the study. The team members for this study will include the Project Manager,
in-house Clinical Research Associate, Regional Clinical Research Associates,
Project Assistant, Trial Design & Development staff member, Clinical Reviewer
and Biostatistician. In addition, a weekly conference call with Vicor will be
coordinated by the HCRI Project Manager and Inhouse Clinical Research Associate
and will include a review of study timelines and milestones as well as any other
issues which may arise during the course of the study_
SITE MANAGEMENT AND MONITORING
HCRI understands that the management of study sites is fundamental to the
success of a clinical trial. Being able to work collaboratively with study
sponsors and site personnel assures a more efficient and timely study execution.
Contact with sites on a regular basis ensures pertinent information will be
forwarded in a timely fashion to the appropriate resources.
Clinical Operations will be directed by HCRI's Clinical Site Manager who
has over 18 years of Site Management and Monitoring experience.
HCRI Site Management will staff this trial with experienced in-house staff
and contract monitors with an expertise in monitoring clinical trials specific
to this disease indication and ensure that enough staff is available to meet the
needs of the trial.
Site Management services for the study will be performed by HCRI in
accordance with the task matrix. Services include site selection, regulatory
document collection, site agreements, site payments and site start-up and close
out. The site monitors will be subcontracted from Monitor for Hire, a firm
specializing in contract study monitors.
DATA MANAGEMENT
INVESTIGATORS' MEETING
Appropriate project team individuals will be identified to attend
Investigator Meetings. These individuals are typically from the Project
Management, Site Management and Trial Design/Development Departments. These
individuals discuss their role in the project and review specific processes
being performed at HCRI. At Vicor's request, the Project Manager and Inhouse
Clinical Research Associate can provide training in specific HCRI procedures
which will apply to the study. The Trial Design/Development representative is
available to review the protocol and trial design issues.
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007 8
Harvard Clinical Research Institute, Inc. o VICOR Technologies, Inc.
--------------------------------------------------------------------------------
DATABASE PROGRAMMING
A study-specific tracking database will be developed to track the arrival
of source documents (for use by the Clinical Reviewer) and ECGs and ICD's.
DATABASE MAINTENANCE
The IT Department oversees export of data from the trial database (resident
at Target) to SASTM for analysis by HCRI's Biostatistics group.
DATA RECEIPT & TRACKING
The tracker reviews, stamps, initials and sends the source documents to the
file room for inclusion in the patient's folder. Original source documents will
be forwarded to off-site storage and a working copy will be used by the Clinical
Reviewer. All working copies of the source documents will be kept in the HCRI
file room. The file room uses a barcode system to log the source documents in
and out.
ADMINISTRATION
Administration consists of several components that are critical to a study.
HCRI maintains file rooms for the original and working file copies of the source
documents. The working (yellow) copy of the source document, once it has been
data entered, is maintained in the file room and access is maintained on a
secure basis. The original copy is filed in a secure location. At the conclusion
of the study, HCRI can arrange for secure long-term storage of the source
documents and other study documents, or the documents can be boxed and forwarded
to the sponsor for storage.
STATISTICAL ANALYSIS & REPORTING
STATISTICAL ANALYSIS PLAN
The Statistical Analysis Plan (SAP) is a comprehensive and detailed
description of the methods and presentation of data analyses proposed for a
clinical trial prior to database locking and treatment code unblinding, in order
to avoid post hoc decisions that may affect the interpretation of the
statistical analysis. A unique SAP is designed for every study at HCRI.
The analysis plan is finalized prior to data analysis and before database
locking and treatment code unblinding, to provide full details, and includes
templates of tables, listings, and figures to be presented in the statistical
report. The SAP contains a statement of the objectives of the trial, as stated
in the protocol. The SAP also refers to any relevant literature review, the
clinical development plan and results from any other similar trials, as
appropriate. The SAP includes a definition of all the populations to be analyzed
(e.g., intention-to-treat, as-randomized, per-protocol).
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007 9
Harvard Clinical Research Institute, Inc. o VICOR Technologies, Inc.
--------------------------------------------------------------------------------
DSMB REPORTS
Two (2) reports will be generated for the DSMB. DSMB reports consist of the
tables described in the DSMB charter, and are assembled by a biostatistician and
statistical programmer. The Chief Medical Officer reviews the reports for
completeness and accuracy before they are sent to the members of the DSMB.
12 M (PRIMARY ENDPOINT) REPORT
The final summary report will include all the analyses specified in the
SAP. The final clinical study report will be reviewed by all the team members,
as well as the Chief Scientific Officer, Chief Medical Officer and any outside
core laboratories. HCRI statisticians will prepare the tables, figures and
listings, and the report will be written by Target Health. Vicor's report will
also be reviewed by several physicians and statisticians who have been advising
the company on its trial design, endpoints and sample size.
6 M (SECONDARY ENDPOINT) REPORT
The secondary endpoint report will include all the analyses specified in
the SAP. The study report will be reviewed by all the team members, as well as
the Chief Scientific Officer, Chief Medical Officer and any outside core
laboratories. HCRI statisticians will prepare the tables, figures and listings.
Vicor's report will also be reviewed by several physicians and statisticians who
have been advising the company on its trial design, endpoints and sample size.
DSMB SERVICES & REPORTING
HCRI will manage Data Safety and Monitoring Board (DSMB) services for this
study. A DSMB charter will be generated by the Chief Medical Officer, for
approval by the DSMB. DSMB members will be identified (either by Vicor or Vicor
and HCRI), and HCRI will negotiate and execute confidentiality and consulting
agreements with the members. The Project Manager/Clinical Site Manager will
schedule DSMB teleconferences, and manage the production of the DSMB report
while remaining blinded to the results.
The reports are generated from live data, which has not completed the
"cleaning" process. The report is reviewed by the Chief Medical Officer and the
Biostatistics Department before being distributed to the DSMB.
CEC SERVICES
HCRI has established a standing Clinical Events Committee-under the
guidance of the CMO, Xxxxxx Xxxxxx, MD. CEC members are chosen based on their
clinical expertise have no association with any trial for which they adjudicate
events. The CEC drafts and agrees upon its working charter for each study prior
to performing any work. Clinical events related to the primary and secondary
endpoints are identified through the use of edit checks pre-specified by Xx.
Xxxxxx and the project team to identify potential endpoint related events. After
review of the identified events by the Clinical Reviewer, support documentation
for identified events is obtained from the site, if necessary, and a summary is
written to describe the significant details of the event. These summaries, with
appropriate support documentation, are presented to the physician members of the
CEC at regularly scheduled CEC Meetings held at HCRI. The results of the
adjudications are entered into the Complications database after the CEC meeting.
The Complications database is specifically created within the overall study
database and is used in the preparation of DSMB reports, as well as in all
analyses of endpoint results.
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007 10
Harvard Clinical Research Institute, Inc. o VICOR Technologies, Inc.
--------------------------------------------------------------------------------
BUDGET ASSUMPTIONS AND NOTES:
ESTIMATES CONTAINED HEREIN:
The Estimated Budget for this Agreement is based upon the Project
Parameters and Project Responsibilities detailed above. Should any of these
Parameters or Responsibilities change, HCRI will prepare and submit a Contract
Change Order as detailed in Section 5(b) of this Agreement.
DOCUMENTS AND DELIVERABLES:
All study documents and deliverables shall be delivered by HCRI in
accordance with timelines established. The determination of deliverable
timelines shall reflect the reporting requirements of Vicor together with the
operational requirements of HCRI. All study documents (e.g., reports) will
require two. (2) drafts before finalization. Vicor will submit one (1) set of
consolidated comments for the review of all draft documents and deliverables.
HCRI processing time requirements for delivery of initial draft documents and
deliverables are specified as shown below.
Costs are based on 2006 labor rates. HCRI reserves the right to review and
renegotiate labor rates with Vicor on an annual basis.
Travel costs for attending and participating in the Investigators' Meeting
are not included. Actual travel costs will be invoiced to Vicor on a time and
materials basis. Meeting expenses will be invoiced to Vicor as a pass-through
expense.
Costs for face-to-face project meetings with Vicor are not included in the
budget. Should face-to-face project meetings be held, HCRI will invoice Vicor on
a time and materials basis for actual time associated with meeting attendance.
Travel expenses (flight, lodging, food) associated with this proposal, if any,
will be invoiced as a pass-through expense.
Estimated costs for ECG Core Laboratory services have been provided. Vicor
will be invoiced for actual ECG Core Laboratory costs as a pass-through expense
based on the actual number of readings conducted at a rate of $75 per ICD
interrogation and $60 per ECG read.
Estimates for DSMB participant costs have been estimated at a rate of
$4,000 per meeting and will be invoiced to Vicor separately based upon the
actual number of meetings held.
CEC physician costs will be invoiced at a rate of $350 per actual event
adjudicated by the CEC.
HCRI will invoice Vicor for any printing, shipping, or binding required
during the course of the project as a pass-through expense.
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007 11
--------------------------------------------------------------------------------
EXHIBIT B
SCHEDULE OF FEES
----------------
The fees identified below will be paid by VICOR to HCRI for the services
described in this Agreement.
TRIAL SITE SITE TOTAL
SERVICES MONITORING PAYMENTS
commencement of work $214,910 $124,880 $135,000 $474,790
Upon enrollment of 100 patients $68,571 $50,576 $77,083 $196,230
Upon enrollment of 200 patients $68,571 $50,576 $77,083 $196,230
Upon enrollment of 300 patients $68,571 $50,576 $77,083 $196,230
Upon enrollment of 400 patients $68,571 $50,576 $77,083 $196,230
Upon enrollment of 500 patients $68,571 $50,576 $77,083 $196,230
Upon enrollment of 600 patients $68,571 $50,576 $77,083 $196,230
Upon enrollment of 700 patients $68,571 $50,576 $77,083 $196,230
Upon enrollment of 800 patients $68,571 $50,576 $77,083 $196,230
Upon enrollment of 900 patients $68,571 $50,576 $77,083 $196,230
Six months post first patient enrolled $67,500 $67,500
Twelve months post first patient enrolled $180,000 $180,000
Eighteen Months post first patient enrolled $219,375 $219,375
Twenty Four months post first patient enrolled $185,625 $185,625
Twenty Seven months post first patient enrolled $78,750 $78,750
three months post last patient enrolled $92,631 $50,576 - $143,207
six months post last patient enrolled $68,571 $50,576 - $119,147
nine months post last patient enrolled $108,831 $50,576 - $159,407
Twelve months post last patient enrolled $68,571 $50,576 - $119,147
Upon delivery of first annual safety report $17,745 - $17,745
Upon delivery of second annual safety report $17,745 - $17,745
Upon delivery of 6 month secondary endpoint -
report $24,060 $24,060
Upon delivery of 12 month primary endpoint $40,260 - $40,260
report
---------------------------------------------------------------------------
Total Milestones $1,270,460 $782,371 $1,560,000 $3,612,831
---------------------------------------------------------------------------
TO BE BILLED MONTHLY AS INCURRED
ECG $243,250 $243,250
CEC participant costs $94,500 $94,500
DSMB participant costs $12,000 $12,000
---------------------------------------------------------------------------
Subtotal $349,750 $349,750
---------------------------------------------------------------------------
---------------------------------------------------------------------------
Grand Total $1,620,210 $782,371 $1,560,000 $3,962,581
===========================================================================
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007
Harvard Clinical Research Institute, Inc. o VICOR Technologies, Inc.
--------------------------------------------------------------------------------
Payments of $86,440 and $247,753 have been made by VICOR under the two (2)
separate Preliminary Services Agreements dated June 14, 2004 and April 5, 2006,
respectively. The total payments of $334,193 will be deducted from the Execution
of Agreement milestone payment under this Agreement.
VICOR agrees to pay each invoice upon receipt of the invoice. Accounts not
paid within thirty (30) days of receipt of an invoice will be considered
overdue.
In the event the Agreement is terminated prior to reaching a payment
milestone, VICOR agrees to pay HCRI for a pro-rated portion of the milestone on
a time and materials basis for actual work performed and documented.
PAYMENT INSTRUCTIONS:
BY CHECK:
---------
Checks should be payable to "Harvard Clinical Research Institute, Inc."
All funds must be remitted in US Dollars
Contact: Xxxx Xxxxxxxxxx @ HCRI # (000) 000-0000
Regular Mail:
-------------
Harvard Clinical Research Institute, Inc. X.X. Xxx 000000
Xxxxxx, XX 00000
Overnight Carriers:
-------------------
Harvard Clinical Research Institute, Inc. Lockbox Department
1VIMF250
00 Xxxxx Xxxx
Xxxxxxx, XX 00000
BY WIRE TRANSFER:
-----------------
Account Name: Harvard Clinical Research Institute, Inc.
Account Number: 1105095700
Bank Name: Citizens Bank
870 Xxxxxxxxxxx
Xxxxxxxxxx, XX 00000
ABA Number: 000000000
Bank Telephone: (000) 000-0000
FTL 321721.1
--------------------------------------------------------------------------------
VICAR PD2i Cardiac Analyzer CTSA (VIC00) (Final)
Date: March 16, 2007 2
