exv4w75



 







    Exhibit 4.75



 




    Change
    Order Number 3



 


 


	 	 	 
	

    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.
    

	

    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 order number 2 dated 8th of June
    2006 shall remain in full force and effect.



 



    3. The value of this Change Order shall be £29,620
    in direct fees and £260,795 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 1 March 2007
    


	
 
	
    DATE 28 February 2007
    

	
 
	
 
	
 

	

    SIGNED Alan Cooke
    


	
 
	
    SIGNED Sean Leech
    



















 







    Appendix 1



 




    1.  Introduction



 



    The main changes to the project specifications are the following:



 


			
	 	    • 
	
    The patient numbers have been amended from 240 to 290 enrolled

	 
	 	    • 
	
    The clinical team allocation has been revised in line with the
    planned monitoring visit schedule (table 4) thus allowing
    for a reduced number of monitoring visits

	 
	 	    • 
	
    Study sites have decreased from 30 to 27 from July 2006 (reduced
    by 1 in Italy, 1 in UK and 1 in Portugal)

	 
	 	    • 
	
    The official Close Out visits will now be performed as part of
    the Open Label extension study as agreed with Amarin. It is
    assumed that during the last monitoring visit for the core study
    an additional 4 hours time on site will be added to allow
    for the final collection of all the core study data (as the
    close out visits will be deferred to the end of the extension
    phase). Therefore, costs associated with resource and travel for
    the close out activity has been removed from this revised
    costing.

	 
	 	    • 
	
    Study Timelines: The overall study timelines have been
    decreased in line with the revised milestone dates as outlined
    in the table 1 below. This allows for further cost reductions

	 
	 	    • 
	
    Staff Allocation: The revised staff allocation in presented
    in table 3. This is now in line with the revised study timelines
    and planned monitoring visit schedule.

	 
	 	    • 
	
    Medical Writing Cost for both studies (AN01.01.0011 and
    AN01.01.0012) not previously included in the contract are now
    included in this change order. These costs have been previously
    presented to and agreed by Amarin Neuroscience and attached
    hereafter as Appendix 3 (Cost Proposal Medical Writing
    Version 1, 4 July 2006).

	 
	 	    • 
	
    Data Management: The Data Management specifications have
    now been revised to include additional activities related to the
    increased patient numbers. The revised costs also include a
    reduction of month activities due to the revised study timelines
    (reduced by 1 month)

	 
	 	    • 
	
    Pass Through Cost: The pass through costs have been
    revised. This includes a reduction for CRA travel and an
    increase for Investigator fees

	 
	 	    • 
	
    Inclusion of a number of unscheduled visits: These visits
    will be performed at sites where issues have arisen. These
    visits will help to resolve any issue regarding Monitoring and
    Case Report Form query collection and resolution. The ICON
    clinical team have proposed the inclusion of 14 additional
    visits for the core study for these activities. It is
    anticipated that these visits may be required close to database
    lock. Each additional monitoring visit in additional to the
    monitoring visit plan as presented in table 4, will be
    billed to Amarin at a rate of £1,119 per visit. This
    unit cost based on 8 hours time on site, 6 hours
    travel time and 4 hours preparation/follow up (18 hrs/unit).




 




    2.  Revised
    Clinical Project Specifications



 



    The revised study timelines are presented below:



 


	 	 	 
	

    Milestones for Study Extension


	
 
	

    Timelines



	 

	

    ICON involvement begin
    


	
 
	
    1st of
    April 2005
    

	

    First patient in
    


	
 
	
    15th of
    December 2005
    

	

    Last patient screened (if
    applicable)
    


	
 
	
    End June 2006
    

	

    Last patient randomized (if
    applicable)
    


	
 
	
    End July 2006
    

	

    Last patient off treatment
    


	
 
	
    End January 2007
    

	

    Last patient out
    


	
 
	
    End February 2007
    

	

    DBL
    


	
 
	
    End March 2007
    

	

    Double Blind Study completed
    


	
 
	
    End June 2007
    



















 






    Table 1



 



    The site, country and patient distribution is detailed in the
    table below.



 


	 	 	 	 	 	 	 	 	 
	

    Country


	
 
	
    Sites
	
 
	
 
	
    Number of Patients
	
 

	 

	

    Austria
    


	
 
	
 
	
    2
	
 
	
 
	
 
	
    29
	
 

	

    Germany
    


	
 
	
 
	
    9
	
 
	
 
	
 
	
    87
	
 

	

    Italy
    


	
 
	
 
	
    3
	
 
	
 
	
 
	
    52
	
 

	

    Portugal
    


	
 
	
 
	
    1
	
 
	
 
	
 
	
    6
	
 

	

    Spain
    


	
 
	
 
	
    4
	
 
	
 
	
 
	
    30
	
 

	

    UK
    


	
 
	
 
	
    8
	
 
	
 
	
 
	
    86
	
 

	

    Total


	
 
	
 
	
    27
	
 
	
 
	
 
	
    290
	
 









 




    Table
    2



 



    Staff Allocation:



 



    Based on the requested changes and patient distribution the
    clinical study team allocation has been revised as follows:



 


	 	 	 	 	 	 	 
	

    FTE


	
 
	
 
	

    Staff


	
 
	

    Time Allocation



	 

	
 
	
    0.4
	
 
	
 
	
    Project Manager
    
	
 
	
    Allocated in April 2005
    

	
 
	
    0.8
	
 
	
 
	
    Project Manager
    
	
 
	
    Allocated from
    1st of
    May 2005 through
    31st of
    December 2005
    

	
 
	
    0.6
	
 
	
 
	
    Project Manager
    
	
 
	
    Allocated from
    1st of
    January 2006 through
    31st of
    March 2006
    

	
 
	
    0.8
	
 
	
 
	
    Project Manager
    
	
 
	
    Allocated from
    1st of
    April 2006 through
    31st of
    31st March
    2007
    

	
 
	
    0.2
	
 
	
 
	
    Project Manager
    
	
 
	
    Allocated from
    1st of
    April 2007 through
    31st of
    June 2007
    

	
 
	
    1.5
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated in April 2005
    

	
 
	
    3.0
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    May 2005 through
    31st of
    December 2005
    

	
 
	
    2.8
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    January 2006 through
    31st of
    March 2006
    

	
 
	
    4.6
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    April 2006 through
    30th of
    September 2006
    

	
 
	
    3.6
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    October 2006 through
    31st of
    December 2006.
    

	
 
	
    3.5
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    January 2007 through
    28th of
    February 2007.
    

	
 
	
    3.0
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated in March 2007
    

	
 
	
    0.8
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated in April 2007
    

	
 
	
    0.7
	
 
	
 
	
    Clinical Research Assistant
    
	
 
	
    Allocated in April 2005
    

	
 
	
    1.4
	
 
	
 
	
    Clinical Research Assistants
    
	
 
	
    Allocated from
    1st of
    May 2005 through
    31st of
    December 2005
    

	
 
	
    1.2
	
 
	
 
	
    Clinical Research Assistants
    
	
 
	
    Allocated from
    1st of
    January 2006 through
    31st of
    March 2006
    

	
 
	
    1.4
	
 
	
 
	
    Clinical Research Assistants
    
	
 
	
    Allocation from
    1st of
    April 2006 through
    30th
    of September 2006
    

	
 
	
    1.3
	
 
	
 
	
    Clinical Research Assistants
    
	
 
	
    Allocation from
    1st of
    October 2006 through
    28th of
    February 2007
    

	
 
	
    1.1
	
 
	
 
	
    Clinical Research Assistants
    
	
 
	
    Allocated in March 2007
    

	
 
	
    0.6
	
 
	
 
	
    Clinical Research Assistants
    
	
 
	
    Allocated in April 2007
    

	
 
	
 
	
 
	
 
	
    Therapeutic Director
    
	
 
	
    Allocated for 5 days for study
    duration
    

	
 
	
 
	
 
	
 
	
    Clinical Regulatory Compliance
    Associate
    
	
 
	
    Allocated for 17 days for
    study duration
    

	
 
	
 
	
 
	
 
	
    Accounting Administrator
    
	
 
	
    Allocated for 69 days for
    study duration
    



















 







    Table
    3



 




    3.  Detailed
    monitoring visit plan



 



    The table below represents the detailed monitoring visit
    schedules as discussed with the Amarin Clinical team



 


	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	

    CRA


	
 
	

    Country


	
 
	
    Site
	
 
	
 
	
    Oct
	
 
	
 
	
    days
	
 
	
 
	
    Nov
	
 
	
 
	
    days
	
 
	
 
	
    Dec
	
 
	
 
	
    days
	
 
	
 
	
    Jan
	
 
	
 
	
    days
	
 
	
 
	
    Feb
	
 
	
 
	
    days
	
 

	 

	

    James
    


	
 
	
    UK
    
	
 
	
 
	
    11
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    UK
    
	
 
	
 
	
    12
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
    UK
    
	
 
	
 
	
    14
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
    UK
    
	
 
	
 
	
    15
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 

	
 
	
 
	
    UK
    
	
 
	
 
	
    16
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
    UK
    
	
 
	
 
	
    18
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    UK
    
	
 
	
 
	
 
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
    6
	
 
	
 
	
 
	
    6
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
    3
	
 

	

    Leena
    


	
 
	
    UK
    
	
 
	
 
	
    13
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    UK
    
	
 
	
 
	
    17
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    UK
    
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    2
	
 

	
 
	
 
	
    Ger
    
	
 
	
 
	
    31
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	

    Corinna
    


	
 
	
    Ger
    
	
 
	
 
	
    35
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
    Ger
    
	
 
	
 
	
    37
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    Ger
    
	
 
	
 
	
    39
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
    Aus
    
	
 
	
 
	
    91
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
    Aus
    
	
 
	
 
	
    92
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    Ger
    
	
 
	
 
	
 
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    6
	
 
	
 
	
 
	
    6
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
    3
	
 

	
 
	
 
	
    Ger
    
	
 
	
 
	
    32
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Julia
    


	
 
	
    Ger
    
	
 
	
 
	
    33
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    Ger
    
	
 
	
 
	
    34
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
    Ger
    
	
 
	
 
	
    36
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
    Ger
    
	
 
	
 
	
    38
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
    Ger
    
	
 
	
 
	
 
	
 
	
 
	
 
	
    5
	
 
	
 
	
 
	
    5
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    Port
    
	
 
	
 
	
    41
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	

    Pedro
    


	
 
	
    ESP
    
	
 
	
 
	
    61
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    ESP
    
	
 
	
 
	
    62
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
    ESP
    
	
 
	
 
	
    63
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    ESP
    
	
 
	
 
	
    64
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    0
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    5
	
 
	
 
	
 
	
    5
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    5
	
 
	
 
	
 
	
    5
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    4
	
 

	

    Silvia
    


	
 
	
    ITA
    
	
 
	
 
	
    71
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    ITA
    
	
 
	
 
	
    74
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
    ITA
    
	
 
	
 
	
    73
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    5
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
    1
	
 
	
 
	
 
	
    1
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    2
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    4
	
 
	
 
	
 
	
    5
	
 
	
 
	
 
	
    5
	
 
	
 
	
 
	
    3
	
 
	
 
	
 
	
    3
	
 

	

    Totals


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    15
	
 
	
 
	
 
	
    35
	
 
	
 
	
 
	
    16
	
 
	
 
	
 
	
    40
	
 
	
 
	
 
	
    18
	
 
	
 
	
 
	
    41
	
 
	
 
	
 
	
    28
	
 
	
 
	
 
	
    60
	
 
	
 
	
 
	
    16
	
 
	
 
	
 
	
    33
	
 



















 







    Table
    4



 




    4.
    Revised Cost Estimates (Clinical)



 


	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	
 
	
 
	
 
	
 
	
 
	
    Number of

    
	
 
	
 
	
    Price per

    
	
 
	
 
	
 
	
 

	

    Clinical Research Management


	
 
	
    Units
	
 
	
 
	
    Units
	
 
	
 
	
    Unit*
	
 
	
 
	
    Total (STG£)
	
 

	 

	

    Clinical Research Associate
    


	
 
	
 
	
    Days
	
 
	
 
	
 
	
    (84
	
    )
	
 
	
 
	
    513
	
 
	
 
	
 
	
    (43,076
	
    )

	

    Clinical Research Assistant
    


	
 
	
 
	
    Days
	
 
	
 
	
 
	
    (23
	
    )
	
 
	
 
	
    400
	
 
	
 
	
 
	
    (9,211
	
    )

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    CLINICAL RESEARCH MANAGEMENT
    SUB-TOTAL


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £(52,851
	
    )

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 









 


	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	
 
	
 
	
 
	
 
	
    Number of

    
	
 
	
 
	
    Price per

    
	
 
	
 
	
 
	
 

	

    Estimated Pass-Through Costs


	
 
	

    Units


	
 
	
    Units
	
 
	
 
	
    Unit
	
 
	
 
	
    Total (STG£)
	
 

	 

	

    Travel


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Site Visit Unit Cost Adjustment
    


	
 
	
    Visits
    
	
 
	
 
	
    (25
	
    )
	
 
	
 
	
    300
	
 
	
 
	
 
	
    (7,500
	
    )

	

    Investigator Fees


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Investigator Fees
    


	
 
	
    Patient
    
	
 
	
 
	
    50
	
 
	
 
	
 
	
    4,900
	
 
	
 
	
 
	
    245,000
	
 

	

    Pharmacy Fees
    


	
 
	
    Site
    
	
 
	
 
	
    (3
	
    )
	
 
	
 
	
    340
	
 
	
 
	
 
	
    (1,020
	
    )

	

    Hospital Overheads
    


	
 
	
    0% per patie
    
	
 
	
 
	
    50
	
 
	
 
	
 
	
    490
	
 
	
 
	
 
	
    24,500
	
 

	

    Other


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Mobile phones
    


	
 
	
    CRA per mo
    
	
 
	
 
	
    (4.4
	
    )
	
 
	
 
	
    42
	
 
	
 
	
 
	
    (185
	
    )

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £260,795
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    CLINICAL RESEARCH
    TOTAL


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £(52,851
	
    )

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    ESTIMATED PASS THROUGH
    COSTS


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £260,795
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    OVERALL TOTAL


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £207,944
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 



















 







    Table
    5



 



    Note: Cost for each additional monitoring visit will be billed
    at a rate of £1,119 per unit (visit).



 




    5.  Revised
    Cost Estimates (Data Management)



 


	 	 	 	 	 	 	 	 	 
	

    Data Management Activity


	
 
	

    Description


	
 
	

    Resource/Time/Duration


	
 
	
    CO Value
	
 

	 

	

    Project Management
    


	
 
	
    Increase in Project Management due
    to the increase in the number of pages processed. (reduction
    in the project timelines by one month has been included in the
    costs)
    
	
 
	
    Additional Project Management Time
    Required
    
	
 
	
 
	
    £6,765
	
 

	

    Scanning: increase in number of
    pages: 5008
    


	
 
	
    Increase in the number of pages
    
	
 
	
    Additional Resource Time Required.
    
	
 
	
 
	
    £2,934
	
 

	

    Data Entry: increase in number of
    pages: 5008
    


	
 
	
    Increase in the number of pages
    
	
 
	
    Additional Resource Time Required.
    
	
 
	
 
	
    £9,354
	
 

	

    Validation: increase in number of
    pages 5008. Cost includes increase in obvious corrections
    and Data Listings also.
    


	
 
	
    Increase in the number of pages
    
	
 
	
    Additional Resource Time Required.
    
	
 
	
 
	
    £17,430
	
 

	

    Queries: increase in number of
    queries from 2182 to 2682. Total increase 500.
    


	
 
	
    Increase in the number of queries
    
	
 
	
    Additional Resource Time Required.
    
	
 
	
 
	
    £4,636
	
 

	

    Coding: increase in number of
    coded terms from 4680 to 5802. Total increase 1122
    


	
 
	
    Increase in the number of coded
    terms
    
	
 
	
    Additional Resource Time Required.
    
	
 
	
 
	
    £971
	
 

	

    Close Out Activity
    


	
 
	
 
	
 
	
    Additional Resource Time Required.
    
	
 
	
 
	
    £1,727
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Total


	
 
	
 
	
 
	
 
	
 
	
 
	
    £43,816
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 









 



    NOTE: Awaiting confirmation of Biostats Specs/Costs are not
    included in the above grid. Stats Timelines may change



 




    6.  Change
    Order Cost Summary



 


	 	 	 	 	 
	

    ICON Service


	
 
	
    Total Cost (GBP)
	
 

	 

	

    Clinical Research Management Europe
    


	
 
	
 
	
    (52,851
	
    )

	

    Data Management
    


	
 
	
 
	
    43,816
	
 

	

    Medical Writing AN01.01.0011
    


	
 
	
 
	
    20,999
	
 

	

    Medical Writing AN01.01.0012
    


	
 
	
 
	
    17,656
	
 

	
 
	
 
	
 
	
 
	
 

	

    Sub-total
    (ICON Service)


	
 
	
 
	
    £29,620
	
 

	
 
	
 
	
 
	
 
	
 









 


	 	 	 	 	 
	

    Estimated Pass-Through Costs


	
 
	
    Total Cost (GBP)
	
 

	 

	

    Clinical Research Management Europe
    


	
 
	
 
	
    260,795
	
 

	
 
	
 
	
 
	
 
	
 

	

    Sub-total
    (ICON Service)


	
 
	
 
	
    £260,795
	
 

	
 
	
 
	
 
	
 
	
 

	

    Total Study Cost
    Estimate


	
 
	
 
	
    £290,415
	
 

	
 
	
 
	
 
	
 
	
 



















 







    Appendix 2-Payment
    Schedule



 


	 	 	 	 	 
	

    Change Order Clinical Direct
    Fee Value: −£52,851


	
 
	
 
	
 
	
 

	

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


	
 
	
 
	
    £(5,282
	
    )

	

    Monthly Payments x 1 months
    in Feb 07 (for period Jan 07 — Feb 07)
    


	
 
	
 
	
    £(15,856
	
    )

	

    Monthly Payments x 4 months
    (Mar07 — Jun07) −£7,928 per month
    


	
 
	
 
	
    £(31,712
	
    )

	

    Change Order Direct Fee Value:
    £82,471


	
 
	
 
	
 
	
 

	

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


	
 
	
 
	
    £8,247
	
 

	

    Monthly Payments x 1 month in
    Feb 07 ( for the period Jan ’07 to Feb ’07)
    


	
 
	
 
	
    £24,742
	
 

	

    Monthly Payments x 4 months
    (Mar ’07 to June ’07) £12,371 per month
    


	
 
	
 
	
    £49,484
	
 

	

    SUMMARY: Change Order 2 Payment
    Schedule


	
 
	
 
	
 
	
 

	

    Change Order Direct Fee Value:
    Clinical
    


	
 
	
 
	
    £82,473
	
 

	

    Change Order Direct Fee Value:
    Data Management
    


	
 
	
 
	
    £(52,850
	
    )

	
 
	
 
	
 
	
    £29,623
	
 

	

    SUMMARY OF COSTS (CHANGE
    ORDER #3)


	
 
	
 
	
 
	
 

	

    10% upon signature
    


	
 
	
 
	
    £2,962
	
 

	

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


	
 
	
 
	
    £8,886
	
 

	

    Monthly Payments x 4 months
    (Mar ’07 to Jun ’07) £4,443 per month
    


	
 
	
 
	
    £17,772
	
 

	
 
	
 
	
 
	
    £29,620
	
 









 




    REVISED
    ICON EU PAYMENT SCHEDULED (CHANGE ORDER #3)



 




    Milestone
    Payments



 


	 	 	 	 	 
	

    Task Completed


	
 
	
    Contract Value
	
 

	 

	

    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
	
 

	

    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


	
 
	
 
	
    £1,399,147
	
 

	
 
	
 
	
 
	
 
	
 









 




    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
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Total Monthly
    payments


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £603,064
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Total payments


	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £2,002,211