exv4w72



 







    Exhibit 4.72



 




    Change
    Order Number 4



 


			
	
    DATED 		
    the
    18th January
    2007
	 
	
    BETWEEN 		
    Amarin Neuroscience Limited of Magdalen Centre North, Oxford
    Science Park, Oxford OX4 4GA UK (‘Amarin’)
	 
	
    AND 		
    ICON Clinical Research Limited of South County Business Park,
    Leopardstown, Dublin 18 (‘ICON’)
	 
	
    WHEREAS: 		

	 
	
    A. 		
    The parties entered into an Agreement for Services on
    30th June
    2005, concerning Study known as Protocol
    AN01.01.0012 — A Multi-centre, double-blind,
    randomized, parallel group, placebo-controlled trial of
    ethyl-epa (Ethyl-Icosapent) in patients with Huntington’s
    Disease. This is a Europe only study as amended by Change
    Order #2 dated
    8th of
    June 2006 and Change Order #3 dated
    30th of
    November 2006.
	 
	
    B. 		
    The parties have agreed to certain change to the services to be
    provided and the associated cost as set out herein.



 




    IT IS
    AGREED BY THE PARTIES AS FOLLOWS:



 



    1. The parties agree to amend the Agreement to reflect
    changes set out in the Appendix 1 which is attached hereto
    and incorporated hereby.



 



    2. Save as otherwise provided in this Change Order, all the
    terms and conditions of the Agreement dated the
    30th June
    2005 and subsequent change orders shall remain in full force and
    effect.



 



    3. The value of this Change Order shall be £573,158
    in direct fees and £364,500 in pass through
    costs. The payment schedule has been revised and attached herein
    as Appendix 2.













 






    IN WITNESS WHEREOF, the parties hereto have executed this
    Change Order by their duly authorised representatives on the
    date(s) written below.



 


	 	 	 
	

    Amarin Neuroscience Limited


	
 
	

    ICON Clinical Research Limited



	 

	

    NAME Alan Cooke
    


	
 
	
    Mr. Sean Leech
    

	

    TITLE CFO, Director
    


	
 
	
    TITLE: Executive VP
    Commercial &

    Organisational Development.
    

	

    DATE 15 February 2007
    


	
 
	
    DATE 29 January 2007
    

	

    SIGNED Alan Cooke
    


	
 
	
    SIGNED Sean Leech
    



















 







    Appendix 1



 


		
	
    1.  
	
    Introduction




 



    The main changes to the project specifications are the following:



 


			
	 	    • 
	
    Management of the one year Open Label
    Follow-Up
    trial to the Phase III study entitled “A multi-centre,
    double-blind, randomized, parallel group, placebo-controlled
    trial of Miraxion (ethyl-EPA) in patients with mild to moderate
    Huntington’s Disease in Europe” (AN01.01.0012).

	 
	 	    • 
	
    Study Timelines:  The overall study timelines
    have been assumed in line with the revised milestone dates as
    outlined in Table 1 below.

	 
	 	    • 
	
    It is assumed that 261 patients will roll over into this
    study extension. It is assumed that all 27 sites participating
    in the double-blind study will participate in the open label
    study also. The total number of patients to roll over into the
    extension study is based on 90% of the number of patients
    randomized in the main study. It is assumed that final site
    distribution will be as detailed in Table 2 below.

	 
	 	    • 
	
    Staff Allocation:  This is in line with the
    study extension timelines and the assumed number of monitoring
    visits to be undertaken per site. The clinical team proposed by
    ICON to conduct this study is illustrated in Table 3 below. This
    allocation is based on the participation of 27 sites in the
    project. During the double blind phase only the monitoring of
    Informed Consent forms for patients entering the extension study
    will be undertaken. A total of 4 monitoring visits (including
    the close-out visit) will be performed at each site. The first
    monitoring visit will occur in March/April, follow up visits
    will be scheduled at the 4 month safety
    follow-up
    and the second at the end of 12 months. The maximum
    allocation of each member to the extension study, in terms of a
    full-time equivalent (FTE) and main task required for each
    period are detailed in Table 3 below:

	 
	 	    • 
	
    Source document verification is restricted to Informed Consent,
    SAEs/AEs and 20% of patients full check of CRF data versus
    source.

	 
	 	    • 
	
    The official Close-Out visits for the overall study (core and
    extension phase) will now be performed as part of the Open Label
    extension study as agreed with Amarin.

	 
	 	    • 
	
    Data Management:  The Data Management
    specifications have been proposed for the study extension and
    are presented in Section 3 below.




 


		
	
    2.  
	
    Clinical
    Research Management




 


		
	
    2.1  
	
    Clinical
    Research Specifications




 



    The revised study timelines are presented below:



 


	 	 	 
	

    Milestones for Study Extension


	
 
	

    Timelines — Open Label Study



	 

	

    ICON involvement begin
    


	
 
	
    15 July 2006
    

	

    First patient in
    


	
 
	
    September 2006
    

	

    Last patient in
    


	
 
	
    End January 2007
    

	

    Last patient off treatment
    


	
 
	
    31 January 2008
    

	

    Last patient out
    


	
 
	
    28 February 2008
    

	

    Data Base Lock
    


	
 
	
    Mid Apr 2008
    

	

    Open Label Study completed
    


	
 
	
    Jun 2008
    









 




    Table
    1



 












 





	 	 	 	 	 	 	 	 	 
	
 
	
 
	
 
	
 
	
 
	
    Number of

    
	
 

	

    Country


	
 
	
    Sites
	
 
	
 
	
    Patients
	
 

	 

	

    Austria
    


	
 
	
 
	
    2
	
 
	
 
	
 
	
    25
	
 

	

    Germany
    


	
 
	
 
	
    9
	
 
	
 
	
 
	
    77
	
 

	

    Italy
    


	
 
	
 
	
    3
	
 
	
 
	
 
	
    52
	
 

	

    Portugal
    


	
 
	
 
	
    1
	
 
	
 
	
 
	
    5
	
 

	

    Spain
    


	
 
	
 
	
    4
	
 
	
 
	
 
	
    26
	
 

	

    UK
    


	
 
	
 
	
    8
	
 
	
 
	
 
	
    76
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Total


	
 
	
 
	
    27
	
 
	
 
	
 
	
    261
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 









 




    Table
    2



 




    Revised
    Staff Allocation:



 


	 	 	 	 	 	 	 	 	 
	

    FTE


	
 
	
 
	

    Staff


	
 
	

    Time Allocation


	
 
	

    Main Tasks to be Performed



	 

	
 
	
    0.6
	
 
	
 
	
    Project Manager
    
	
 
	
    Allocated in April 2007
    
	
 
	
    General Management: Status
    tracking, Finance, Drug supply, Team training and follow up of
    1 month follow up visit. Hand Over preparation.
    

	
 
	
    0.3
	
 
	
 
	
    Project Manager
    
	
 
	
    Allocated in May 2007
    
	
 
	
    General Management and Hand Over
    activities.
    

	
 
	
    —
	
 
	
 
	
    Project Manager
    
	
 
	
    Allocated in June 2007
    
	
 
	
    Allocation for the core study as
    presented in C/O#3 will apply during this period. No additional
    allocation was assigned
    

	
 
	
    0.3
	
 
	
 
	
    Lead CRA
    
	
 
	
    Allocated from
    1st of
    May 2007 through
    31st of
    May 2008
    
	
 
	
    Starting May 2007 with handover
    activities. General Management of extension study
    (teleconferences, status updates and team management).
    

	
 
	
    0.6
	
 
	
 
	
    Clinical Research Associate
    
	
 
	
    Allocated from
    1st of
    July 2006 through
    31st of
    December 2006
    
	
 
	
    Set up time applied July-Sept now
    extended from July-Dec 06. Preparation of documentation and
    assist in submission to EC/CA, collection of essential
    documents, investigator agreements and Study Initiation.
    

	
 
	
    —
	
 
	
 
	
    Clinical Research Associate
    
	
 
	
    1st of
    January 2007 through
    31st of
    March 2007
    
	
 
	
    Additional clinical team
    allocation for study extension was not assigned during this
    period
    

	
 
	
    2.6
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated in April 2007
    
	
 
	
    Site visits to monitor informed
    consent, SAEs/AEs, for 20% of patients, performance of a full
    check of CRF data versus source and monitoring month 7 follow up
    visit.
    

	
 
	
    1.4
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    May 2007 through
    30th of
    June 2007
    
	
 
	
    Follow up activities from April
    2007.
    














 





	 	 	 	 	 	 	 	 	 
	

    FTE


	
 
	
 
	

    Staff


	
 
	

    Time Allocation


	
 
	

    Main Tasks to be Performed



	 

	
 
	
    2.6
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    July 2007 through
    31st of
    August 2007
    
	
 
	
    All sites to be visited to collect
    4 month safety follow up data, including SAEs/AEs and for
    20% of patients, performance of a full check of CRF data versus
    source.
    

	
 
	
    0.6
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    September 2007 through
    31st of
    December 2007
    
	
 
	
    General tasks will be preformed
    during this period
    

	
 
	
    2.6
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    January 2008 through
    31st of
    May 2008
    
	
 
	
    In Jan and Feb all sites will need
    to be visited to collect 12 month follow up data. From
    March through May all sites will need to be visited for formal
    close out. Performance of study closure activities including
    study file finalization/reconciliation.
    

	
 
	
    1.2
	
 
	
 
	
    Clinical Research Assistant
    
	
 
	
    Allocated from
    15th of
    April 2007 through
    31st of
    May 2007
    
	
 
	
    Overall support to Lead CRA and
    CRAs; Set up and maintenance of ICOTrack,  Main study file,
    Monitoring files, Document control, CRF distribution, Drug
    supply tracking, Investigator Payments and support to sites.
    

	
 
	
    0.7
	
 
	
 
	
    Clinical Research Assistant
    
	
 
	
    Allocated from
    1st of
    June 2007 through
    31st of
    August 2007
    
	
 
	
    As above
    

	
 
	
    0.5
	
 
	
 
	
    Clinical Research Assistant
    
	
 
	
    Allocated from
    1st of
    September 2007 end
    30th of
    November 2007
    
	
 
	
    As above
    

	
 
	
    0.7
	
 
	
 
	
    Clinical Research Assistant
    
	
 
	
    Allocated from
    1st of
    December 2007 end
    30th of
    April 2008
    
	
 
	
    In addition to above, final study
    file preparation/reconciliation.
    

	
 
	
 
	
 
	
 
	
    Clinical Regulatory Compliance
    Associate
    
	
 
	
    Allocated for 12 days for the
    extension study duration
    
	
 
	
 

	
 
	
 
	
 
	
 
	
    Accounting Administrator
    
	
 
	
    Allocated for 30 days for the
    extension study duration
    
	
 
	
 









 





 




			
	
    Note: 		
    General site management, in-house study management and status
    reporting is calculated from April 07 onwards Some time per
    month is calculated for regular team teleconferences and 1:1
    conversations with Lead CRA



 



    Table 3













 





		
	
    2.2  
	
    Direct
    Cost Estimates (Clinical)




 


	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	
    Clinical Research

    
	
 
	
 
	
 
	
    Number of

    
	
 
	
 
	
    Price per

    
	
 
	
 
	
 
	
 

	

    Management


	
 
	
    Units
	
 
	
    Units
	
 
	
 
	
    Unit*
	
 
	
 
	
    Total (STG£)
	
 

	 

	

    Project Manager
    


	
 
	
    Days
    
	
 
	
 
	
    17
	
 
	
 
	
 
	
    970
	
 
	
 
	
 
	
    16,484
	
 

	

    Lead CRA
    


	
 
	
    Days
    
	
 
	
 
	
    74
	
 
	
 
	
 
	
    696
	
 
	
 
	
 
	
    51,548
	
 

	

    Clinical Research Associate
    


	
 
	
    Days
    
	
 
	
 
	
    562
	
 
	
 
	
 
	
    529
	
 
	
 
	
 
	
    297,089
	
 

	

    Clinical Research Assistant
    


	
 
	
    Days
    
	
 
	
 
	
    169
	
 
	
 
	
 
	
    407
	
 
	
 
	
 
	
    68,746
	
 

	

    Clinical Regulatory Compliance
    Associate
    


	
 
	
    Days
    
	
 
	
 
	
    12
	
 
	
 
	
 
	
    561
	
 
	
 
	
 
	
    6,728
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    CLINICAL RESEARCH MANAGEMENT
    SUB-TOTAL


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £440,595
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 









 


	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	
 
	
 
	
 
	
 
	
    Number of

    
	
 
	
 
	
    Price per

    
	
 
	
 
	
 
	
 

	

    Support Services


	
 
	
    Units
	
 
	
    Units
	
 
	
 
	
    Unit*
	
 
	
 
	
    Total (STG£)
	
 

	 

	

    Local Ethics Committee Study
    Extension Submissions
    


	
 
	
    Sites
    
	
 
	
 
	
    21
	
 
	
 
	
 
	
    276
	
 
	
 
	
 
	
    5,797
	
 

	

    Central Ethics Committee Study
    Extension Submission
    


	
 
	
    Sites
    
	
 
	
 
	
    6
	
 
	
 
	
 
	
    414
	
 
	
 
	
 
	
    2,484
	
 

	

    Regulatory Submission for Study
    Extension
    


	
 
	
    Submission
    
	
 
	
 
	
    6
	
 
	
 
	
 
	
    1,502
	
 
	
 
	
 
	
    9,015
	
 

	

    ICOTrack Maintenance
    


	
 
	
    Months
    
	
 
	
 
	
    24
	
 
	
 
	
 
	
    177
	
 
	
 
	
 
	
    4,238
	
 

	

    SUPPORT SERVICES
    SUB-TOTAL


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £21,534
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    ICON CLINICAL RESEARCH
    MANAGEMENT FEE


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £462,129
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 









 





 




			
	
    * 		
    Figures in the “Price per unit” column have been
    rounded, figures in the “Total” column are Correct.



 



    Table 4













 





 


		
	
    2.3  
	
    Pass-through
    Estimates (Clinical)




 


	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	
 
	
 
	
 
	
 
	
    Number of

    
	
 
	
 
	
    Price per

    
	
 
	
 
	
 
	
 

	

    Estimated Pass-Through Costs


	
 
	

    Units


	
 
	
    Units
	
 
	
 
	
    Unit
	
 
	
 
	
    Total (STG£)
	
 

	 

	

    Travel


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Site Visit Unit Cost Adjustment
    


	
 
	
    Visits
    
	
 
	
 
	
    81
	
 
	
 
	
 
	
    300
	
 
	
 
	
 
	
    24,300
	
 

	

    Team Meetings
    


	
 
	
    Meetings
    
	
 
	
 
	
    1
	
 
	
 
	
 
	
    629
	
 
	
 
	
 
	
    629
	
 

	

    Sponsor Meetings
    


	
 
	
    Meetings
    
	
 
	
 
	
    2
	
 
	
 
	
 
	
    1,118
	
 
	
 
	
 
	
    2,236
	
 

	

    Translations


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Protocol synopsis (1,000 words)
    


	
 
	
    Language
    
	
 
	
 
	
    5
	
 
	
 
	
 
	
    391
	
 
	
 
	
 
	
    1,953
	
 

	

    Informed consent document
    


	
 
	
    Language
    
	
 
	
 
	
    5
	
 
	
 
	
 
	
    783
	
 
	
 
	
 
	
    3,917
	
 

	

    EC documents
    


	
 
	
    Submission
    
	
 
	
 
	
    21
	
 
	
 
	
 
	
    433
	
 
	
 
	
 
	
    9,085
	
 

	

    Medication instructions
    


	
 
	
    Language
    
	
 
	
 
	
    5
	
 
	
 
	
 
	
    120
	
 
	
 
	
 
	
    600
	
 

	

    Regulatory documents
    


	
 
	
    Submission
    
	
 
	
 
	
    5
	
 
	
 
	
 
	
    866
	
 
	
 
	
 
	
    4,330
	
 

	

    Patient Cards
    


	
 
	
    Language
    
	
 
	
 
	
    5
	
 
	
 
	
 
	
    53
	
 
	
 
	
 
	
    265
	
 

	

    Investigator Contracts
    


	
 
	
    Site
    
	
 
	
 
	
    19
	
 
	
 
	
 
	
    800
	
 
	
 
	
 
	
    15,200
	
 

	

    Other


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Teleconferencing (3 lines)
    


	
 
	
    Meetings
    
	
 
	
 
	
    48
	
 
	
 
	
 
	
    84
	
 
	
 
	
 
	
    4,025
	
 

	

    Investigator Fees
    


	
 
	
    Patients
    
	
 
	
 
	
    261
	
 
	
 
	
 
	
    950
	
 
	
 
	
 
	
    247,950
	
 

	

    Ethics Committee Fees
    


	
 
	
    Sites
    
	
 
	
 
	
    27
	
 
	
 
	
 
	
    559
	
 
	
 
	
 
	
    15,094
	
 

	

    Regulatory Fees
    


	
 
	
    Submission
    
	
 
	
 
	
    6
	
 
	
 
	
 
	
    800
	
 
	
 
	
 
	
    4,800
	
 

	

    Courier
    


	
 
	
    per site/month
    
	
 
	
 
	
    648
	
 
	
 
	
 
	
    15
	
 
	
 
	
 
	
    9,631
	
 

	

    Mobile phones
    


	
 
	
    per CRA per month
    
	
 
	
 
	
    30
	
 
	
 
	
 
	
    42
	
 
	
 
	
 
	
    1,243
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £345,259
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 









 



    Table 5













 





		
	
    3.  
	
    Data
    Management




 


		
	
    3.1  
	
    Data
    Management Specifications




 



    ICON Data Management will apply the same standards and implement
    the same processes for the extension study as we are currently
    using for the core study. The specifications for the extension
    study are outlined below:



 


	 	 	 	 	 
	

    Activity


	
 
	

    Unit Type


	
 
	

    Specification



	 

	

    Project Management


	
 
	
 
	
 
	
 

	

    Study Duration:
    


	
 
	
    Month
    
	
 
	
    12*
    

	

    Frequency of Status Reports:
    


	
 
	
    Monthly
    
	
 
	
    12
    

	

    Meetings


	
 
	
 
	
 
	
 

	

    Teleconferences with Amarin
    (weekly):
    


	
 
	
    Hours/Meeting
    
	
 
	
    1 x 48
    

	

    Face to Face Meetings:
    


	
 
	
    Hours/Meeting
    
	
 
	
    1 x 20
    

	

    Project
    Set-up


	
 
	
 
	
 
	
 

	

    Updates to study documentation:
    


	
 
	
    Documentation
    
	
 
	
    Yes
    

	

    Modification of existing database:
    


	
 
	
    Database Panel
    
	
 
	
    18
    

	

    Modification of existing data
    listings:
    


	
 
	
    Listings
    
	
 
	
    Yes
    

	

    Additional edit check programs:
    


	
 
	
    Program
    
	
 
	
    220
    

	

    Program External Data and
    Review


	
 
	
 
	
 
	
 

	

    Central laboratory interface:
    


	
 
	
    Laboratory
    
	
 
	
    12
    

	

    Genetic & EFA interface:
    


	
 
	
    Interface
    
	
 
	
    No
    

	

    Data Processing


	
 
	
 
	
 
	
 

	

    Total Number of Patients
    


	
 
	
 
	
 
	
 

	

    Drop-out patients:
    


	
 
	
    Patient
    
	
 
	
    0
    

	

    Completed patients:
    


	
 
	
    Patient
    
	
 
	
    261 (ext)
    

	

    Total pages processed:
    


	
 
	
    Page
    
	
 
	
    7830
    

	

    Coding


	
 
	
 
	
 
	
 

	

    Coded Terms (60% autoencode):
    


	
 
	
    Item
    
	
 
	
    1436
    

	

    Query Processing


	
 
	
 
	
 
	
 

	

    Data Queries:
    


	
 
	
    Query
    
	
 
	
    783
    

	

    Data Transfers to
    Amarin


	
 
	
 
	
 
	
 

	

    Final Transfer:
    


	
 
	
    Transfer
    
	
 
	
    1
    

	

    Quality Control
    Reviews


	
 
	
 
	
 
	
 

	

    100% Reviews of CRFs:
    


	
 
	
    Patients
    
	
 
	
    16
    

	

    Critical Variable Reviews (20
    items):
    


	
 
	
    Patients
    
	
 
	
    261
    

	

    Closeout Activities


	
 
	
 
	
 
	
 

	

    Return of CRFs to Amarin:
    


	
 
	
    Pages
    
	
 
	
    7830
    

	

    Other Activities


	
 
	
 
	
 
	
 

	

    SAE Reconciliation:
    


	
 
	
    SAE
    
	
 
	
    30
    









 





 




			
	
    * 		
    Please note that we have included an additional 12 project
    months for the extension study on the basis that costs up to
    JUNE 2007 are including in the main study.



 



    Note: ICON has assumed the number of coded terms and the
    query rate based on previous experience. If ICON finds there is
    a significant differences in these figures throughout course of
    the study, Amarin will be notified immediately and a review of
    the costs associated with these items shall occur.



 



    Note: Total Number of Pages are based on the following
    assumption: that the extension study runs for one year it is
    estimated that all patients will complete the first 4
    visits — Visit 4(5 pages), Telephone Visit (5), Visit
    5 (9) and Visit 6 (11).













 





 




    Table
    6



 




    Reconciliation
    of Serious Adverse Events



 



    ICON will perform SAE reconciliation. ICON will perform SAE
    Reconciliation between the Clinical Database and the Kendle
    Database. This will be done on a monthly basis. It will take
    approximately 1 hour to reconcile each SAE.



 




    Case
    Record Form Scanning



 



    ICON will scan all CRFs received into the OptICON system. ICON
    will file and store the CRFs in a secure and confidential manner
    throughout the course of the study.



 


		
	
    3.2  
	
    CRF
    Design Specifications




 



    ICON will design two additional unique Case Record Form (CRF)
    pages for the extension study (using Framemaker). Amarin will
    review and approve these pages prior to release.



 


		
	
    3.3  
	
    Direct
    Cost Estimates (Data Management)




 



    These costs are based on the assumption that Data Management
    will be done in Europe



 


	 	 	 	 	 
	

    Data Management Activity


	
 
	
    Costs GBP
	
 

	 

	

    Project Management
    


	
 
	
 
	
    £20,975
	
 

	

    Revisions to database and
    development of new edit checks
    


	
 
	
 
	
    £12,816
	
 

	

    Meetings and teleconferences
    


	
 
	
 
	
    £6,940
	
 

	

    External Data Review and
    Reconciliation
    


	
 
	
 
	
    £891
	
 

	

    CRF Page Scanning
    


	
 
	
 
	
    £4,567
	
 

	

    Data Entry
    


	
 
	
 
	
    £14,588
	
 

	

    Validation
    


	
 
	
 
	
    £29,372
	
 

	

    Queries
    


	
 
	
 
	
    £8,658
	
 

	

    Coding
    


	
 
	
 
	
    £1,517
	
 

	

    Data Transfers
    


	
 
	
 
	
    £348
	
 

	

    SAE Reconciliation
    


	
 
	
 
	
    £2,428
	
 

	

    Quality Reviews
    


	
 
	
 
	
    £5,357
	
 

	

    CRF Redesign Costs
    


	
 
	
 
	
    £2,572
	
 

	
 
	
 
	
 
	
 
	
 

	

    TOTAL ADDITIONAL DATA
    MANAGEMENT COSTS


	
 
	
 
	
    £111,029
	
 

	
 
	
 
	
 
	
 
	
 









 





 





    NOTE 1: Data Management costs are based on the
    specifications outlined in section 3.1 and may be deemed as
    “ballpark” until the final specifications for the
    extension study have been agreed.



 



    NOTE 2: Biostatistics costs have not been included at
    this time as we await confirmation of ICON’s involvement in
    this activity and agreement of the final specifications.



 



    Table 7













 





		
	
    3.4  
	
    Pass-through
    Costs Estimates (Data Management)




 


	 	 	 	 	 
	
 
	
 
	
    Total Cost

    
	
 

	

    Activity


	
 
	
    (GBP)
	
 

	 

	

    Teleconferencing
    


	
 
	
 
	
    £874
	
 

	

    Communication
    


	
 
	
 
	
    £2,524
	
 

	

    Travel
    


	
 
	
 
	
    £3,747
	
 

	

    CRF Printing
    


	
 
	
 
	
    £11,096
	
 

	

    CRF Distribution
    


	
 
	
 
	
    £1,000
	
 

	
 
	
 
	
 
	
 
	
 

	

    Total Cost


	
 
	
 
	
    £19,241
	
 

	
 
	
 
	
 
	
 
	
 









 



    Table 8



 


		
	
    4.  
	
    Cost
    Summary




 


	 	 	 	 	 
	

    ICON Service


	
 
	
    Total Cost (GBP)
	
 

	 

	

    Clinical Research Management Europe
    


	
 
	
 
	
    462,129
	
 

	

    Data Management
    


	
 
	
 
	
    111,029
	
 

	
 
	
 
	
 
	
 
	
 

	

    Sub-total
    (ICON Service)


	
 
	
 
	
    £573,158
	
 

	
 
	
 
	
 
	
 
	
 









 


	 	 	 	 	 
	

    Estimated Pass-Through Costs


	
 
	
    Total Cost (GBP)
	
 

	 

	

    Clinical Research Management Europe
    


	
 
	
 
	
    345,259
	
 

	

    Data Management
    


	
 
	
 
	
    19,241
	
 

	
 
	
 
	
 
	
 
	
 

	

    Sub-total
    (ICON Service)


	
 
	
 
	
    £364,500
	
 

	
 
	
 
	
 
	
 
	
 

	

    Total Study Cost
    Estimate


	
 
	
 
	
    £937,658
	
 

	
 
	
 
	
 
	
 
	
 









 




    Table
    9













 







    Appendix 2-Payment
    Schedule



 


	 	 	 	 	 
	

    Change Order Clinical Direct
    Fee Value: £462,129


	
 
	
 
	
 
	
 

	

    Initial Payment 10% on signature
    of Change Order (Feb 07)
    


	
 
	
 
	
    £46,213
	
 

	

    Monthly Payments x 1 month
    Feb 07 (for the period July06 — Feb 07)
    


	
 
	
 
	
    £138,640
	
 

	

    Monthly Payments x 16 months
    (Mar07 — Jun08) £17,330 per month
    


	
 
	
 
	
    £277,280
	
 

	

    Change Order Direct Fee Value:
    £111,029


	
 
	
 
	
 
	
 

	

    Initial Payment 10% on signature
    of Change Order (Feb 07)
    


	
 
	
 
	
    £11,103
	
 

	

    Monthly Payments x 1 month
    Feb 07 (for the period July06 — Feb 07)
    


	
 
	
 
	
    £33,304
	
 

	

    Monthly Payments x 16 months
    (Mar07 — Jun08) £4,163 per month
    


	
 
	
 
	
    £66,608
	
 

	

    SUMMARY: Change Order 2 Payment
    Schedule


	
 
	
 
	
 
	
 

	

    Change Order Direct Fee Value:
    Clinical
    


	
 
	
 
	
    £462,133
	
 

	

    Change Order Direct Fee Value:
    Data Management
    


	
 
	
 
	
    £111,015
	
 

	
 
	
 
	
 
	
    £573,148
	
 

	

    SUMMARY OF COSTS (CHANGE
    ORDER #4)


	
 
	
 
	
 
	
 

	

    10% upon signature
    


	
 
	
 
	
    £57,315
	
 

	

    Monthly Payments x 1 month
    Feb 07 (for the period July06 — Feb 07)
    


	
 
	
 
	
    £171,944
	
 

	

    Monthly Payments x 16 months
    £21,493 (Mar07 — Jun08)
    


	
 
	
 
	
    £343,888
	
 

	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
 
	
    £573,147
	
 

	
 
	
 
	
 
	
 
	
 









 




    REVISED
    ICON EU PAYMENT SCHEDULED (CHANGE ORDER #4)



 


	 	 	 	 	 
	

    Milestone Payments


	
 
	
    Contract Value
	
 

	 

	

    Task Completed


	
 
	
 
	
 
	
 

	

    Contract Signed
    


	
 
	
 
	
    342,550
	
 

	

    All sites initiated
    


	
 
	
 
	
    192,684
	
 

	

    50% of patients enrolled
    


	
 
	
 
	
    192,684
	
 

	

    Initial Payment 10% on signature
    of C/O#2
    


	
 
	
 
	
    25,984
	
 

	

    Initial Payment 10% on signature
    of C/O#3
    


	
 
	
 
	
    2,962
	
 

	

    Initial Payment 10% on signature
    of C/O#4
    


	
 
	
 
	
    57,315
	
 

	

    100% of patients enrolled
    


	
 
	
 
	
    192,684
	
 

	

    Mid-point of treatment phase
    


	
 
	
 
	
    192,684
	
 

	

    All patients completed and data at
    DM
    


	
 
	
 
	
    192,684
	
 

	

    All sites closed
    


	
 
	
 
	
    38,537
	
 

	

    Final Tables & Listings
    


	
 
	
 
	
    25,691
	
 

	
 
	
 
	
 
	
 
	
 

	

    Total Milestones
    payments


	
 
	
 
	
    £1,456,462
	
 

	
 
	
 
	
 
	
 
	
 









 


	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	

     Monthly Payments


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Monthly Payments contract
    


	
 
	
    April ‘05 - Jan’ 07
    
	
 
	
 
	
    22
	
 
	
 
	
 
	
    15,570
	
 
	
 
	
 
	
    342,550
	
 

	

    Monthly Payments change
    order #2
    


	
 
	
    Jun ‘06 - May’ 07
    
	
 
	
 
	
    12
	
 
	
 
	
 
	
    19,488
	
 
	
 
	
 
	
    233,856
	
 

	

    Monthly Payments change
    order #3
    


	
 
	
    Feb’ 07
    
	
 
	
 
	
    1
	
 
	
 
	
 
	
    8,886
	
 
	
 
	
 
	
    8,886
	
 

	

    Monthly Payments change
    order #3
    


	
 
	
    Mar ‘07 - June’ 07
    
	
 
	
 
	
    4
	
 
	
 
	
 
	
    4,443
	
 
	
 
	
 
	
    17,772
	
 

	

    Monthly Payments change
    order #4
    


	
 
	
    Feb’ 07
    
	
 
	
 
	
    1
	
 
	
 
	
 
	
    171,944
	
 
	
 
	
 
	
    171,944
	
 

	

    Monthly Payments change
    order #4
    


	
 
	
    Mar ‘07 - June’ 08
    
	
 
	
 
	
    16
	
 
	
 
	
 
	
    21,493
	
 
	
 
	
 
	
    343,888
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Total Monthly
    payments


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £1,118,896
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Total payments


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £2,575,358