Examination of Witness (Questions 380
- 399)
TUESDAY 28 JULY 1998
DR PETER
LEWIS
Chairman
380. Dr Lewis, good afternoon and thank you
very much indeed for coming along to the Science and Technology
Select Committee to assist us in our inquiry into British Biotech
this afternoon. You have been kind enough to send us written evidence
so far and we will refer to that in a moment or two. We understand
that you resigned from British Biotech last year and that you
now are the Chief Executive of a company called Prolifix. We were
hoping this afternoon that you would come along perhaps as an
independent witness, as independent as you can be, to tell us
about the unfortunate happenings at British Biotech, and we understand
that you have some sympathy with the company, British Biotech,
which employed you for five years or so, but in the Mail on
Sunday, this last Sunday, there is quite a substantial article
that indicates that for the last two years you have been receiving
monthly payments from British Biotech, £2,000 a month up
until recently, £1,000 a month at the present time. We only
found this out of course yesterday and we have to wonder now whether
you are in any sense at all an independent witness or whether
you are just another voice from the Biotech payroll, so my first
question is could you please explain the situation to us?
(Dr Lewis) Certainly, Chairman. There
is nothing underhand at all about these arrangements. As I said
in my memorandum, when I resigned from the Board of British Biotech,
which was at the end of June last year, I made some severance
arrangements with British Biotech or, rather, they made them with
me. I was effectively fired from the company and I had a one-year
rolling contract with the company and I argued that I was entitled
to a year's salary in recompense for being let go. In the event,
there was a negotiation and I was offered six months' severance
pay which I accepted and I elected to take that money as half
pay for twelve months in a consultancy agreement, so I was actually
on half of my previous salary for twelve months. I did not actually
receive all that money because I did not anticipate that I would
take another full-time job. In fact as part of the severance arrangements,
I said that I would like to take the severance payment like that
as a consultant because it would also enable me to do other consultancy
work and I had in mind at that point that I would not take a full-time
job, that I would look around the industry for a while and I would
take up non-executive positions possibly or consultancy work,
and in fact I did that. I got one non-executive position with
a small company in Israel and I was offered several others which
I did not take. However, in December of 1997, five months after
I stepped down from the Board, I received a very attractive offer
to become full-time Chief Executive of a biotech company. By that
time, I had spent five months doing consultancy work and going
around the place and what-not and I was rather bored with it and
I thought it would be nice to get back to a full-time job, so
I accepted the full-time job. I went back to British Biotech and
said, "I have got this full-time job. Would you like to vary
the arrangement? I think you owe me seven months' pay on this
consultancy agreement". Their response was, "Well, that's
too bad. You've got another full-time job. You can't be an employee
in two companies", fine, "so the arrangement is terminated".
I felt a little hard-done-by at this and I said, "Well, it's
unfair. This money was in fact a severance payment on losing my
job as R&D Director and coming off the Board. I would like
some further compensation", so in the event we had a negotiation
and I was offered a somewhat lower, a very much lower compensation
of £1,000 a month for a part-time, or fully a consultancy
for twelve months. I informed obviously my new employers of this
fact and in fact it was in the original announcement of my appointment
as Chief Executive of Prolifix. I had sent this announcement out
of courtesy to British Biotech and they asked me not to put in
the fact that I was a consultant to British Biotech. They did
not want that in the announcement for some reason, so I deleted
it. However, the Chairman of my new company and the Board of the
company know perfectly well that I am a part-time consultant to
British Biotech. It is in no way a conflict of interest, as that
newspaper article suggests, and in fact Prolifix and British Biotech
have very different activities and what I actually do for British
Biotech, I have to say, is something of a nominal consultancy
because it was just a way of my receiving a severance payment.
However, I am doing some work for British Biotech. I last went
to British Biotech about three months ago and I have been working
with one of the business development people on evaluating compounds
in the pre-clinical area of the company.
381. Well now, Dr Lewis, you very early on in
that statement said that there is nothing underhand in these payments
and you will note that I never suggested that there was anything
underhand.
(Dr Lewis) Thank you.
382. You then at the end of your statement said
that there is no conflict of interest between your present company
and British Biotech. Again, that was not said, nor implied in
my question.
(Dr Lewis) Thank you.
383. What my question was saying is, whereas
we thought we were going to have someone with a degree of independence
before us this afternoon in answering the questions we wish to
put to him, when we find out that the person whom we thought would
be independent is receiving a monthly payment from the company
that we are investigating, it takes away somewhat the idea that
that individual is independent. That is the point I am making.
(Dr Lewis) I understand that. I cannot argue against
that. I am just explaining that in fact this was a way of my being
severed from the company and it was a pretty normal sort of arrangement
in these circumstances. In fact, I think I am independent. I in
fact thought I was being interviewed here about what had actually
happened during the time I was at British Biotech. I have also
made some observations about biotech in general and I think I
am independent. I am not in any way in the pocket of British Biotech.
384. Well, you are in every way in the pocket
of British Biotech, if I may say so. However, let us proceed,
having declared that we have to be very careful and cautious,
knowing that you receive a monthly payment from British Biotech,
and we have to take that into account when we interpret your answers.
Before my colleagues ask you further questions, we have got your
written evidence, Dr Lewis, and your comments on Dr Millar as
being intelligent, ambitious, articulate, but then you also refer
to the fact that he is opinionated, emotional and difficult to
manage and that you had had a dispute with him at Merrell Dow
and after that dispute, he left after an argument with you about
responsibility and reporting lines.
(Dr Lewis) Yes.
385. Why did you feel you wanted to recruit
Dr Millar to British Biotech when you had previously found him
so difficult to work with?
(Dr Lewis) Well, he has other qualities as I have
said. When I came to British Biotech there was a Director of Clinical
Research; he left very rapidly after I arrived and I was looking
for a new Director of Clinical Research and I rather operate on
the process better the devil you know than the one you do not.
I knew exactly what Andy was like. In fact, before I employed
him we had a long discussion about the previous arguments we had
and he wrote me a letter accepting the job with the phrase in
it "thanks very much for the olive branch". I liked
the guy, I got on well with him, I thought he was energetic and
confident. The row we had at Merrell was about the fact that he
was overly ambitious and he wanted to get control of another branch
of clinical research within Merrell which it was not in my interest
to give him at the time so he went off in a great huff and in
fact he went off to a small company. He told me after he left
that was one of the things he wanted to do, he wanted to work
for a small company rather than an international giant and that
came back to me. He also happened to live near Oxford and it was
convenient for me to employ him. Although he was a difficult man
I thought I knew the depths of his difficulties, as it were, and
I could control him.
386. On 15 May last year, 1997, we understand
that you were shown a copy of Dr Millar's memorandum regarding
the unblinding of clinical trials on 31 March this year. That
cannot be right.
(Dr Lewis) I think you have got it the wrong way round,
Chairman.
387. I beg your pardon.
(Dr Lewis) I was shown the memo during the Cameron
McKenna inquiry in March this year.
388. You were shown it in May. Sorry, the memo
of 15 May you were shown in March.
(Dr Lewis) Yes.
389. Had you any indication before that that
Dr Millar had unblinded those clinical trials of Marimastat and
Zacutex?
(Dr Lewis) No, I had not, absolutely not.
390. Yet I seem to recall that Dr Millar indicated
he had told you.
(Dr Lewis) Yes, he did that. I have read his transcript.
That simply was not the case. I have been back in my mind to 18
months ago to try and think why he thought he might have done
that and I cannot think of any explanation. I was unaware that
he had unblinded those studies. Had I known that he had done so
I would have reacted quite violently because he compromised the
integrity of those studies by unblinding them.
Dr Gibson
391. Dr Lewis, you wrote on 17 May 1998 a handwritten
letter which starts off "Dear Andy, you may be surprised
to hear from me, however I got you into this and I feel responsible
for some of it". Do you remember that letter?
(Dr Lewis) Yes, absolutely.
392. You said in your letter that you told British
Biotech's Chairman, Mr Raisman, that "I did not believe that
you broke the blind but that you did do a bit of safety analysis
on on-going trials". Dr Millar told us that "Peter,
as a doctor, knows very well that looking at deaths to examine
safety gives exactly the same information as looking at deaths
to examine efficacy." Do you agree with that?
(Dr Lewis) That is accurate in one way and not in
others. May I explain?
393. Take the accurate one first.
(Dr Lewis) Yes. It is accurate in that, in fact, if
you look at deaths on a drug and on a placebo then obviously you
would know whether the drug was working or not. However, these
were complicated studies he was looking at. Taking the Marimastat
study, there was one group of patients who were on an injectable
drug and then there were three groups of patients who were on
our drug, the oral Marimastat. It was open as to whether they
were on the injectable comparator drug versus our three groups
of drug. He knew what the death rate in the comparator drug was
and he knew what the death rate was in the three groups of Marimastat
but there was a blinding between the three groups. What he told
me was, and I cannot remember when this was, that the death rate
looked similar in the Marimastat groups and the injectable group.
394. The implication was he thought this was
not worth going on with; is that what you are saying?
(Dr Lewis) It was quite early on and there were few
patients in. He said it was a worry to him and I said "look,
do not worry about it, it is early on in the trial and you do
not know at what stage these patients died anyway, do you"
and he said "no". This was a very serious trial. In
fact, the end point of the trial is when 90 per cent of all the
patients admitted have died. We were expecting deaths to occur.
Whether the drug was working or not better than the comparator
compound was a question of when they died. The other thing about
it was he did not look at the death rates in the three different
groups of our Marimastat drug and one of the Marimastat groups
was on a drug dose that we anticipated was lower than likely to
work. It was not actually a negative question. What I thought
there would be was an active drug which was producing an effect,
a low dose of Marimastat that was probably doing nothing, a middle
dose that was doing something and a high dose that might be doing
quite a bit. That was the anticipated result. Taking the whole
lot together one would not anticipate there would be a marked
difference in mortality if the drug was working.
395. So you put this to him and what did he
say?
(Dr Lewis) He agreed. He said he certainly had not
unblinded the three groups. I said "I do not want you looking
at it again, it will only worry you, it will come out in the wash
at the end, we should just persist in the thing". There had
been quite a lot of troubles with us starting the study anyway
and we just wanted to get the patients into the study as rapidly
as possible.
Dr Jones
396. Could I ask what you know about Dr Millar's
application to the FDA?
(Dr Lewis) To unblind the studies?
397. He applied for permission for an interim
analysis of Study 128.
(Dr Lewis) I know nothing about that. That was after
I left the company. He certainly did not talk about that at all
when I was there.
Mr Beard
398. Dr Lewis, can you tell the Committee what
the significance of unblinding is in terms of developing a new
drug?
(Dr Lewis) All these studies are carried out under
good clinical practice which is a series of rules which enables
them to be eligible to be used by the regulatory authorities to
determine efficacy and safety. Obviously the whole idea of a double
blind study is that neither the patient nor the doctor knows what
treatment they are on. As I mentioned, the Marimastat study was
complicated because it was single blind in some aspects and double
blind in others. Obviously if a patient has some horrible adverse
event individually, they die or something like that when it is
unexpected, which does not apply to a cancer drug because you
are expecting patients to die unfortunately, but in other cases
if a patient dies suddenly for example on a drug for hayfever
then you are in a situation where you have got to unblind the
study as far as that individual patient is concerned to know whether
possibly you have a drug effect or not. There are procedures for
doing that. The whole thing is organised so that you only unblind
the study for that individual patient if necessary. It does not
happen very often. If you do unblind the study outside the rules
of good clinical practice then you invalidate the study.
399. Why?
(Dr Lewis) Because you could be accused of biasing
it. Once you know half the results of the study— It is a
good question, why. It is part of the conventions of once you
have done that. It should not be done. In fact, if you go against
any of the tenets of good clinical practice you risk the study
being invalidated. The authorities are very, very hot on this,
particularly the FDA. Indeed, one of the things that occurred
to me about this unblinding thing was that I had worked in the
States for quite a number of years, Andy never had and maybe he
just did not take these tenets of good clinical practice quite
as strongly as he ought to have done because of that. If you have
worked under the FDA's thumb for a number of years you would never
even dream of unblinding a study, what is the point, you are just
jeopardising what is an extremely expensive exercise and a lot
of time also.
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