1
CONTRACT CLINICAL RESEARCH AGREEMENT
AMENDMENT # 2
--------------------------------------------------------------------------------
Pursuant to the Contract Clinical Research Agreement between ISTA
Pharmaceuticals (formerly known as Advanced Corneal Systems, Inc.) ("ISTA") and
CroMedica Global Inc. ("CroMedica"), dated May 19, 1999, and Amendment #1, dated
October 11, 2000, the following amendment(s) are hereby accepted by both
parties:
ADJUSTMENT TO SCOPE OF SERVICES
As agreed by both parties, the original scope of services provided by CroMedica
Global under the terms of the original contract are hereby revised to reflect
the increase in the number of monitoring visits, extension of project management
services, a revision to the SAE management estimate and increases to the data
management services, while removing unmasked monitoring visits, and the site
audit services.
A revised Attachment 2, Payment and Performance Schedule is attached hereto and
will replace any previous payment and performance schedules.
DATA COLLECTION IN FOLLOW UP PERIOD
This amendment further recognizes that ISTA may have a future need for Data
Management Services in the form of data collection during the 3 year follow up
period to the study. Once the scope of services required by ISTA is defined in
relation to this follow up period, and should it be the desire of ISTA to engage
CroMedica in such work, CroMedica hereby agrees to a today rate of USD $10.00
per CRF page to undertake the additional data collection services.
ACCEPTANCE OF AMENDMENT TO AGREEMENT BY AND BETWEEN:
SPONSOR: CONTRACTOR:
ISTA PHARMACEUTICALS CROMEDICA GLOBAL INC.
----------------------------------- -----------------------------------
NAME: ▇▇▇ ▇▇▇▇▇▇▇
-----------------------------
TITLE: PRESIDENT
-----------------------------
----------------------------------- -----------------------------------
DATE DATE
2
ATTACHMENT 2
PAYMENT AND PERFORMANCE SCHEDULE
REVISED - NOVEMBER 15, 2000
PAYMENT SCHEDULE
Sponsor shall reimburse reasonable costs and expenses at net thirty (30) days
terms upon receipt of invoice and any associated original receipts, and/or at
the occurrence of the below incidents enacted at Sponsor's request, pending
review for acceptableness and/or completeness. All figures are in US dollars:
FIXED-UNIT PRICE PAYMENT STRUCTURE
----------------------------------------------------------------------------------------------
ORIGINAL REVISED
UNIT COST STUDY TOTAL ADJUSTMENT STUDY TOTAL
----------------------------------------------------------------------------------------------
Up front (20%) $563,525 $563,525
----------------------------------------------------------------------------------------------
Australia Regulatory Submission $10,000 10,000 10,000
----------------------------------------------------------------------------------------------
CRF Finalization 8,580 8,580 8,580
----------------------------------------------------------------------------------------------
Site Recruitment:
Canadian 200 2,400 2,400
U.S. 240 2,880 2,880
Australia 240 2,400 2,400
----------------------------------------------------------------------------------------------
Initiation Visits:
Canadian 600 7,200 7,200
U.S. 720 18,720 18,720
Australia 1,080 10,800 10,800
----------------------------------------------------------------------------------------------
Interim Visits:
Canadian 1,200 183,600 276,000
U.S. 1,440 1,156,680 1,741,320
Australia 1,280 124,800 124,800
ADD:
7 additional monitoring
visits per site related to
3 interim analyses and
resolution of clinical
review queries not
originally contracted:
Canadian
11 sites x 7 visits 1,200 92,400
U.S.
58 sites x 7 visits 1,440 584,640
----------------------------------------------------------------------------------------------
REMOVE: Unmasked Visits:
Canadian 900 10,800 (10,800) 0
U.S. 1,080 68,040 (68,040) 0
----------------------------------------------------------------------------------------------
Close Out Visits: 10,800
Canadian 900 10,800 81,000
U.S. 1,080 81,000 9,600
Australia 960 9,600
----------------------------------------------------------------------------------------------
3
------------------------------------------------------------------------------------------------
ORIGINAL REVISED
UNIT COST STUDY TOTAL ADJUSTMENT STUDY TOTAL
------------------------------------------------------------------------------------------------
REMOVE: Site Audits 2,500 125,000 (125,000) 0
------------------------------------------------------------------------------------------------
Australia Investigator Meeting 12,000 12,000 12,000
------------------------------------------------------------------------------------------------
Study Training 24,550 24,550 36,640
ADD: Training for Protocol
Amendment, new CRFs, rescue data
-- CRAs and at sites -- 2 hours
per site.
($75 x 2hr x 11 sites) Canadian 150 1,650
($90 x 2 hr x 58 sites) U.S. 180 10,440
------------------------------------------------------------------------------------------------
SAE Management $300 per SAE 81,600 217,600
ADD: SAE Management Estimate of
272 additional SAEs representing
an overall 80% SAE rate for the $500 per SAE 136,000
study.
------------------------------------------------------------------------------------------------
Database Design 13,500 13,500 17,250
ADD: Additional 50 hours at
$75/hr for creation & distribution
of new CRF forms (BCVA & Efficacy) 3,750
------------------------------------------------------------------------------------------------
Data Entry:
1/3 Data Entered 50,000 50,000 50,000
2/3 Data Entered 50,000 50,000 50,000
3/3 Data Entered 50,000 50,000 50,000
------------------------------------------------------------------------------------------------
ADD: Data Management Services
relating to extra visit, all pts,
at 18 months
Original contract per page value 38,080 38,080
of $4/pg x 8 pgs x 1190 pts
------------------------------------------------------------------------------------------------
Project Management Fees
(per month for 25 months - 5,566 139,150 410,275
rate reflects absorption of fees
in up front payment)
ADD: 15 add'l months 18,075 271,125
(extended to September, 2002)
------------------------------------------------------------------------------------------------
Enrollment Tracking:
Effective October, 2000 - 2,519.71 120,946 120,946
per month for 48 months
------------------------------------------------------------------------------------------------
TOTAL CONTRACT $2,938,571 $934,245 $3,872,816
------------------------------------------------------------------------------------------------
PASS-THROUGH COSTS: SPONSOR shall reimburse CONTRACTOR for reasonable
pass-through costs (e.g., travel, lodging, meals) at net thirty (30) days term
upon receipt of original receipt(s)/invoice. Interest at 15% shall apply if net
thirty (30) days terms are not satisfied.