Examination of Witness (Questions 140
- 160)
WEDNESDAY 1 JULY 1998
DR ANDREW
MILLAR
140. What is your opinion now?
(Dr Millar) My opinion now, since the shareholders
pointed it out, is that they had to restart the study in order
to be consistent with the selling of the shares in January. To
me that is the most plausible construction. At the time I thought
it was because Keith was so optimistic about his company and he
had such belief about his product, he could not see the wood for
the trees.
141. But they did not accept your advice in
1995, why did you not go public with your concerns then?
(Dr Millar) They did accept my advice. That phase
three study never restarted. We finished up, against my better
judgment, starting a very, very limited, phase one type study—three
patients per dose with one-tenth of the dose we had used in the
phase three studies and we rapidly ran into problems with peritonitis.
We did that in October or November. From a personal professional
point of view, I actually regret having restarted that study.
I could see it was going nowhere, because we had not identified
the problem, we had not fixed it, so it was very predictable we
would run into the same problem.
Dr Williams
142. Returning to marimastat, I have two or
three questions. Generally what you have been telling us this
afternoon has been quite depressing and it is the case that any
hopes we had in some of these products, and that you had, were
slowly destroyed, yet with marimastat in your earlier comments
you still rate it not at a 2 per cent prospect of success but
something more like 30 or 40 per cent?
(Dr Millar) Yes. Pancreatic cancer, the first cancer
type we studied, is actually the least likely cancer type on theoretical
grounds you can envisage a drug like marimastat would be effective
against. Patients with pancreatic cancer have got tumours the
size of steaks on dinner plates which are sat right on some really
important clockwork at the back of the peritoneal cavity, and
they have a mortality which is reported in the literature of between
three and six months, but if you look at it carefully it is down
at around five or six weeks. These are very, very sick patients.
A drug which is simply going to stop the rate of growth of a tumour,
on theoretical grounds, you would think is not most likely to
work in that situation. The place in which it is most likely to
make advances is when you have just got the tumour growing on
a cellular basis as pinheads, but the trouble with doing clinical
studies on patients who have got cancers like that is that it
will take 15, 20 years and 2,000 patients. So you are caught in
a cleft stick and just the fact that the drug does not work in
pancreatic cancer in that situation does not in any way, in my
opinion, prove it will not work in other cancer types. It is consistent
with the idea, which I have always entertained as a possibility
or a probability, that it might not work in later stages of the
disease.
143. With these early press releases in 1995-96,
did you feel reasonably satisfied with the hype and the way they
were phrased?
(Dr Millar) My position on these is very strange and
difficult to represent. I had got more experience of the pharmaceutical
industry than anybody else at British Biotech at the time I was
Director of Clinical Research in terms of being a jobbing medical
director in a sales office. I had been a jobbing medical director
in a sales office for five years in Australia and in Japan, I
understood the regulations about what you can say about drugs
and what you cannot say very well. I understand what the medical
profession think in terms of what they want out of statements
about drugs and what you can say and cannot say. When we put out
that first press release on marimastat, I was very concerned indeed
that it would contravene the Medicines Act or the Food, Drugs
and Cosmetics Act, because both of them say, "You will not
promote an unlicensed product." Both of them had got attachments
to the Act—codicils, whatever you call them—about
the ABPI guidelines in the UK, which state that the press releases
which come from companies are considered promotional, and in the
United States they define any statement about efficacy or safety
of a drug as being promotional. So if you put out a press release
which says anything about the efficacy or safety of the drug,
you are actually making a promotional statement, and if the drug
is in clinical research it is about an unlicensed product. So
there is that particular possible contravention. But my second
concern was that it was very preliminary data we had at that time
and putting that preliminary data into the lay press raises hopes
of patients and doctors and causes all sorts of trouble in clinics
up and down the country because everybody goes in and says, "I
want British Biotech's new wonder drug." I was concerned
about that. I represented these concerns very strongly, I was
told that the regulations of the Stock Exchange were overriding
and we had a duty to disclose all available information to them.
144. I do not know whether this is Biotech's
figure or perhaps one imposed by the media but there was potentially
here an £800 million world market. Is that the case? Is it
a 30 or 40 per cent chance of something as wide ranging in its
application as that?
(Dr Millar) In the most optimist scenarios, if marimastat
did work in all common solid cancers at all stages of disease,
I suspect £800 million is an under-estimate of how much drug
you would sell. But if marimastat actually only works like a drug
like Tamoxifen, which is for early stage cancer and for one cancer
type—in the case of Tamoxifen it is breast cancer—the
market is still there but it is about 400 million pounds or dollars,
that sort of magnitude. So 800 million may well be a reasonable
estimate but who knows until you have the data from the studies
and you see how it performs.
Dr Jones
145. You represented Biotech at the SEC inquiry;
could you tell us about that? You say you were obliged to defend
what the executive directors had said in their press releases
and you felt you had been put in an untenable situation. Dr McCullagh
said he did not discuss what you were saying with you, could you
tell us what happened and why you felt obliged in that way?
(Dr Millar) It is very complicated to explain my exact
mental state, but with regard to those press releases that the
SEC were enquiring about I had warned at the time I said, "Listen,
you guys, I know about these things. If I was a regulator and
I was wanting to sort something out on these press releases I
would make an example. Just the fact you say everybody else is
doing it is not a defence against getting a speeding ticket and
it will not be a defence against issuing a press release like
this." I anticipated that we were going to have problems
with those press releases. I was surprised when we did not. It
was not until September or October about ten months after the
press releases that we got the letter from DDMAC, the branch of
the FDA that looks at advertising, to say that they did not like
our press releases. I saw that and thought, "That is quite
interesting. I do not know how that is going to turn out but it
was not my signature on those press releases." I was not
an authorising signature on the press releases at that time. The
Executive Directors were authorising signatures on those press
releases. They carried the signatures of the Executive Directors
and in particular Peter Lewis, and so when the SEC launched their
inquiry and I was elected as the first person to go along and
speak to them I thought this was a bit rich actually that it should
be me as Director of Clinical Research, not an Executive Director,
who is sent along to defend press releases put out by the Executive
Directors. Why am I being sent along? It is because I am an extremely
plausible and knowledgeable presenter on the technical data and
it is actually the company's best chance of justifying these press
releases. With regard to press releases—
146. Did you object?
(Dr Millar) I objected with Peter Lewis. Peter Lewis
said to me, "Remember, Andy, united we stand, divided we
fall". I was just surprised that Paul Littlewood, the company
counsel, was the only person who had spoken to me about going
to see the SEC.
Chairman
147. Was objection at that stage not rather
late? We challenged Dr McCullagh about the fact you stated you
had no responsibility for press releases. The word "responsibility"
can be interpreted in a number of ways but most of us who have
worked in large organisations if there is something going on that
we have had an interest in we make certain that any statement
made about the work we are doing, whether an executive director
or board director, reflects the truth as we see it. We may not
have responsibility in the sense of being a director but we feel
a moral responsibility for the truth to come out for the organisation
we work for. Can you so lightly dismiss responsibility for those
press releases?
(Dr Millar) If you think I am dismissing it lightly
that is not the impression that I am attempting to give. With
regard to the press releases on marimastat the scenario was we
did not have a standard operating procedure for the issuing of
these press releases. What would happen when these marimastat
press releases went out was there would be three or four drafts
zipping around the building and they would be going from executive
director's desk to executive director's desk and I would be running
round the building trying to catch up with what was happening
and trying to tone the press releases down at the same time as
giving my advice that it was better not to issue any press release
but have a meeting in Waterman's Hall where we would speak to
the analysts but we would not be issuing things to the lay press.
It is the lay press I had the most trouble with. I had given my
advice as strongly as I could. With my subordinates I said, "I
am mortified by this." I spoke to Alan Cornish and Peter
Brown and I considered resigning at that time when the press releases
were put out about marimastat. But if I resigned I would not have
been discharging my responsibilities. I finished up toning down
those press releases enormously with the remonstrations that I
made about them. In some way I felt I had exercised my responsibility
and in fact my own view on the press releases on marimastat now
is that they just sail extremely close to the wind. With regard
to regulatory opinion on whether they actually transgress or whether
they are okay, it is really a matter of opinion.
Mr Beard
148. Could I take you along from that to the
beginning of this year when you approached Perpetual, Mercury
Asset Management and Kleinwort Benson. Why did you approach them
at that point? That contrasts rather with the more passive attitude
to the press releases? What were you attempting to achieve by
this?
(Dr Millar) First of all, I did not approach Perpetual.
Perpetual phoned me up when one of the analysts found that she
was unable to speak to me because in June of last year I declined
to take part in company presentations to shareholders and analysts
because I did not support the business plans. This analyst who
knew me over a long period was very concerned she could not meet
the Director of Clinical Research when she had been invited to
cover the stock. Perpetual phoned me. At that time my major concerns
were the decisions we were making on the clinical programmes,
particularly with regard to the dose of marimastat that we were
using in the whole programme and the continuation of the Zacutex
studies which to me looked like they were just wasting our money.
They were very, very big studies and the evidence we had at that
time was that the drug probably was not working, yet we were spending
money at the rate of £60 million a year. £60 million
pays for an awful lot of research. Chiroscience, another biotech
company, managed to operate on around £1Ö million a
month, or £18 million a year. So there were enormous amounts
of over-spend in that 60 million and we were going to run out
of money quickly. I was sat in the company watching us mismanaging
the clinical trials for which I was responsible and wasting our
money, it seemed to me because we had this business charade built
up which was preventing us from confronting reality. When the
shareholders approached me I was entertaining the idea that through
the threat of an extraordinary general meeting they would be able
to bring the business plans back into touch with technical reality,
to level with the public with regard to our prospects of success,
and by doing that take the spend rate down to about £18 million
a year, and to keep our operations going until such time as the
studies on marimastat which we are going to read out in 2002 or
2003 read out and we see whether the drug is working or not.
149. How do you answer the point which was made
earlier, the feeling that you approached them out of malice because
you felt you had been overlooked in the promotion into Dr Lewis'
place?
(Dr Millar) It did coincide with Dr Jensen's appointment,
the time when Jane Henderson, the analyst, phoned me up. They
did coincide. I had actually been looking forward to Dr Jensen
joining the company because I thought at that stage we would get
a medical opinion into the decision-making process which would
rationalise things. But, to be candid with you, within ten minutes
of starting to speak to Dr Jensen I realised that his understanding
of statistics and the probabilities associated with clinical research
was not as advanced as mine. That will sound arrogant but you
have to remember I have a first class degree in engineering and
I am particularly numerate for a doctor. He spoke to me in the
same way as if it had been Dr McCullagh. So he had represented
to me this last chance to put things right, which I always thought
I would be able to do throughout last year and the beginning of
this year. When I spoke to Dr Jensen and I realised this, that
was the second occasion when I requested voluntary redundancy.
150. So you are saying malice and disappointment
at being passed over had no part in your approaching these external
investors?
(Dr Millar) I cannot help but confess that I have
disappointment at being passed over for promotion. I think it
is natural. It is not a nice feeling to have someone brought in
as your superior when you think you can do that job. I have to
confess, of course, I had those thoughts. What you have to judge
is with regard to the substance of what I am saying on a technical
basis, the motives I demonstrated through my actions, whether
my actions are consistent just with being a trouble-maker or consistent
with actually rectifying the business plans of a company to which
I felt, and still do feel, deeply committed.
151. Did you realise at the time you were approaching
them what the consequences were likely to be?
(Dr Millar) I knew I was provoking a serious confrontation
between myself and the board of directors.
Dr Williams
152. Just to establish this clearly on the record,
it is not you who went to Perpetual, it is Perpetual that telephoned
you?
(Dr Millar) Correct.
153. And if Jane Henderson had not telephoned
you this story may not have been broken?
(Dr Millar) I do not know what I would have done if
Jane Henderson had not telephoned me. I knew that something had
to be done and I was in the middle of a lot of rows within the
company within my reporting lines.
154. Could you just give a little bit more background
on how she should have thought you had the views that you did?
(Dr Millar) She phoned me up (I cannot remember the
date but it is somewhere in one of the documents I have given
you). Around June 11 or 12 of last year, because of the degree
of the disagreement I had with Dr McCullagh over the business
plans and over the clinical research programmes, I said I would
not present at any more presentations to shareholders and analysts
because on a personal basis I did not believe that our business
plans, or indeed our press releases, were sensible or indeed truthful
or honest at that stage. That was after the press release on May
12 saying we are going to a get marketing authorisation for Zacutex
or certainly to my mind implied it. Throughout that period I did
not present to analysts. Jane Henderson had just joined Goldman
Sachs when she was invited to cover the stock on behalf of Goldman
Sachs and she tried to arrange a meeting with British Biotech
and to meet me, but when Katie Arber, the PR Manager at British
Biotech, asked me if I would attend that meeting, I said no. So
Jane Henderson was unable to meet with me. Because over the years
I have played a very central part in the interaction of the company
with the analysts and I believe Jane Henderson had a reasonable
opinion of my ability, she was disturbed by that and she phoned
me up in my office three or four times I think altogether and
in the end I finished up saying to her, "Actually, Jane,
I am very concerned about the business plans. I do not know what
to do about it. It is just me against ten directors. Am I right
or am I wrong? How can I do anything about this?"
Chairman: Are there any quick questions by members
of the Committee?
Dr Jones
155. Going back to Zacutex, given your reservations
about it in February/March 1997—you had said that the data
continued to give a pessimistic view—why did you in May
of 1997 advise the Board that the drug had, I think, a 40 per
cent chance of having approval without conditions, a 30 per cent
chance of approval with conditions and therefore an overall chance
of a positive outcome of 68 per cent?
(Dr Millar) This has to be put in careful context.
It has been taken out of context in that circular to shareholders.
156. It is exactly the same—
(Dr Millar) That is my memo. I wrote that memo, absolutely,
on 23 May. On 21 May I presented to the whole board, the executive
directors and the non-executive directors and I showed them an
acetate which until a few weeks ago I kept a copy of—I have
returned it to the company now because of returning all the documents—and
on that acetate it says the estimated chance of approval at the
time of submission was 40 per cent. I was trying to tell the board
that the whole business plan was thoroughly over-egged. 40 per
cent was my realistic perception at the time we submitted the
marketing authorisation application. I said it needs to be discounted
now at that presentation. After that presentation Dr Kirby was
incredibly angry. She walked around the building talking in a
raised voice in a highly critical way about me. I saw Dr McCullagh
or I spoke to him at about 7 o'clock that evening and he told
me, "Dr Kirby is fully justified in being angry. Clinical
research is a complete mess. With a single action you have destroyed
all the work she has been doing over the last eight months."
I did not understand this as a rational explanation of the situation.
What I did know is that I had a supervisor who was extremely angry
and another Executive Director who was extremely angry, and they
appeared not to have taken on board this advice that we needed
caution and I still had to attempt to find some way of bringing
them back to a more realistic view point. That memorandum was
an attempt to find common ground. If I went in there and said,
"Keith, this drug has got a 20 per cent of being approved",
I just would not have communicated. I ended up putting 40 per
cent with conditions, 30 per cent needs discounting. I hinted
in that 40 per cent—
157. It is the other way round.
(Dr Millar) 40 per cent without conditions, needs
discounting, 30 per cent with conditions and in the paragraph
underneath it I said there are some reasons.
158. You put that it was prudent to be more
cautious.
(Dr Millar) Yes because Keith knew at that stage that
the data on 215 indicated that the drug may not work.
Dr Jones: We like prudence around here.
Chairman
159. I must draw this to a conclusion. My final
question to you is do you feel that as a result of your actions
over the last 15 months, where you have stood up for what you
believe to be right, that you have enhanced your reputation as
a clinical trials director and a physician and a medical man or
do you think your reputation is damaged? In answering that question,
would you with hindsight do exactly the same again?
(Dr Millar) Gosh! You can judge my reputation better
than I can. I can just judge—I can just judge—
160. You can just judge what others think perhaps?
(Dr Millar) I can just judge how I feel myself. With
regard to my actions, I regret very much being put in the situation
where I had to undertake the actions which I have undertaken.
I do not know whether they were right or wrong. I regret, after
I was dismissed, the press release. Keith McCullagh told me at
the time of my disciplinary panel—I said, "Will you
put out a press release that I have been dismissed?" He said,
"I have to, it is a price sensitive matter." I knew
at that stage that I was going to be hurled into something. My
actions showed that I was not looking for a media confrontation
at the time of my suspension and indeed when I was phoned up by
that journalist from Sunday Business, I was forced into
it.
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