Annex C
Schedule of documents returned to British
Biotech by Dr A W Millar on 28/5/98
This is a schedule of all original and copy
documents belonging to British Biotech which are in my possession
as of 28/5/98. The documents listed below are returned to British
Biotech under cover of this schedule. British Biotech has acknowledged
receipt of the documents listed in this schedule by signing a
copy of it which I have retained.
Andrew W Millar MRCP FRCS MFPM 29/5/98
For and on behalf of British Biotech. 29 May
1998.
All documents are copies unless otherwise stated
Documents relating to batimastat:
1994
28 September and 5 October (1 original 1 copy
of each)
Memos from Richard Erwin re glass shards as
possible cause of peritonitis
13 October
Memo from AM to 11 people including Keith McCullagh,
Peter Lewis and James Noble
"Intra-peritoneal adverse events and batimastat"
Advises of potential problems and need for caution
in ascites studies
October 14, 18, November 10, 11 and December
15
Telephone reports and correspondence re peritonitis
in batimastat studies
9 November
Letter to Dr David Miles re adverse events
24 November
Memo from Rod Baker re investigation of glass
spicules as cause of peritonitis
19 December x 2
Project team meeting minutes (sent to Peter
Lewis and Keith McCullagh) x 2
"real concerns on the adverse event profile"
18 January x 2
Project team meeting minutes—little mention
of problems, issued on 1 February
25 January
Letter to Professor Reubens to stop recruiting
24 February x 2
Memo to Peter Lewis copied to executive directors
recommending a change of strategy
1 March (original)
Memo from Neil Graham about regulatory requirements
to recommence studies
16 May (original)
Peter Lewis's hand-written changes on draft
batimastat document showing deletion of mention of deaths and
understatement of severity of problems
Documents relating to marimastat:
1996
6 May (1 copy 1 original)
Memo from Greg Hockel attaching draft letter
to FDA re designation of study 128 as phase II or phase III (AM
wanted "potentially pivotal phase II"—FDA objected
to "potentially pivotal")
September 13
Letter from DDMAC stating press releases were
in violation of FDCA
1997
15 May
Memo to Keith McCullagh outlining the unblinded
dosing data from study 128 indicating that marimastat was probably
not as good as gemcitabine at any dose and that Peter Lewis appeared
not to have been transmitting appropriate level of concern and
caution to other executive directors
3 June
Data inconsistent with outcome of pancreatic
cancer study sufficient for registration (shown to Keith McCullagh)
18 June (2.5 copies)
Memo to Keith McCullagh re Marimastat programme
urging caution
6 August
Data inconsistent with outcome of pancreatic
cancer study sufficient for registration
30 December (2 copies)
Request to FDA by Greg Hockel on my instruction
for permission to perform interim analysis (copied to Keith McCullagh
and Paul Littlewood)
1998
8 January (2 copies)
Memo from Greg Hockel to executive directors
to address concern over leaving "a legal paper trail about
data"
9 January (2 copies)
Telephone log between Jean McCarthy and FDA
re above
9th January (2 copies)
e-mail from AWM to Drummond, Fallen and Kirby
re "Furore" over unblinding
14 January (1 original 1 copy)
Four line fax from FDA approving request to
have unblinded interim look at data
19 January (2 copies)
Minutes of development management group minuting
KGM's decision not to unblind data
24 February (2 acetates and copies)
Unblinded data of different dosing groups shown
at Jensen's marimastat "product review board meeting".
Shows probable difference between doses and inferiority to gemcitabine
25 February (2 copies)
Memo from Amy Berrington showing possible significance
of results above and estimating study end for 128 as end of September
1998
Documents relating to lexipafant
1994
28 March (2 copies)
Memo from AM and Lloyd Curtis:
"Minimalist approach . . . provide
a basis for an application for marketing license which could be
shored up at the appeal stages by new data from (other) trials"
May 10, 16 and 17
Three memos (2 from PJL, one from Tony Mitchell),
in the final one of which, Lewis overrules Millar & Curtis
on need for a dose comparison study after intense debate. Millar
and Curtis warn that this will give regulatory and commercial
liability, but finish up shrugging shoulders and accepting written
ruling. (This later becomes major objection of EMEA)
23 June (2 copies)
Front sheet of protocol of study 214 (UK study)
issued as "A phase II . . . study . . ."
17 November (2 copies)
Protocol title changed to "Phase III"
at request of executive directors without change in study design
15 May (full copy of memo with copies of original
worksheets for each unblinding)
KM said "These allegations you are making
against Peter Lewis are very serious—would you be prepared
to back them up in court?" I said yes and gave him every
bit of "ultra-inside" clinical information in writing.
Worksheets demonstrate that unblinding was restricted to overall
intent to treat analysis without any assessment of availability,
categorisation or any other efficacy parameter or medical history.
The procedures were therefore unbiassable and caused no prejudice
to further analyses.
May
Counter-proposal from PL and KM of press release
to correct misleading press releases.
21 May (acetate, hard copy and b/w photocopy)
Presentation to the main board stating the estimated
probability of success of MAA at time of submission was 40 per
cent.
23 May (3 copies)
Memo to KGM, following extremely heated rows
after realistic board presentation and his irrational desire to
do more pancreatitis studies, a diplomatic attempt at finding
common ground before persuading him that less would be more sensible.
8 September
Memo to KGM, following his irrational request
to employ a CRO for the pancreatitis studies, a diplomatic attempt
at finding common ground before I became exasperated and unblinded
study 215 again, proving that it was and always would be negative.
12 September (2 copies)
Memo from KGM reprimanding me after informing
him, Kirby and Fallen of negative outcome of study 215.
Various assessment reports from regulators
DOCUMENTS RELATING
TO CONCEALMENT
OF 6 MONTH
TOXICOLOGY REPORTS
ON MARIMASTAT
1995
19 May R&D management minutes
"marmoset tox data are likely to come from
LSR in late July or early August"
16 June R&D management minutes
"data . . . is due in third week in July"
21 July R&D management minutes
Apologies Alan Drummond
22 September R&D management minutes
"PJL noted that the draft histology report
is due at the end of September"
ASSORTED DOCUMENTS
RELATING TO
OTHER CHRONIC
MANAGEMENT PROBLEMS
6 April 1993
Memo from Peter Lewis ordering large sepsis
study with BB-882 against AWMs advice—this was subsequently
overturned following contact by AWM to David Leathers.
22 September 1995
Memo from Moyna De Selincourt showing routine
for PJL to edit AWM's board report
22 April 1997 (originals)
Correspondence with Kirby on pricing and phase
IV medical matters indicating growing tensions and concerns within
clinical as commercial powerbase becomes disproportionately large
and dangerously out of touch.
23 May 1997
Declining Senior Medical Officer and board position
on BBP
2 June 1997 "Matchbox!!"
Memo re MGI pharma indicating extensive personal
prior knowledge of players and lack of benefit in doing a deal
12 June 1997 (3 copies)
Memo declining to do corporate presentations
26 June 1997 "Umbria!" (2 copies)
Memo re USB indicating extensive personal prior
knowledge of players and products and lack of benefit in doing
a deal
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