Examination of Witnesses (Questions 480
- 499)
TUESDAY 7 DECEMBER 2004
DR ROBERTO
SOLARI, DR
MALCOLM BOYCE
AND MR
HARPAL KUMAR
Q480 Dr Naysmith: Do you think there
are any adverse effects of this not terribly close but close-ish
relationship between the MRC and the drug companies, or some drug
companies?
Dr Solari: Potentially. We have
to be aware that they are businesses and they are run along business
lines. We are here to serve the public good. We have to make sure
that our partnership does not stray into areas where they are
driving our agenda. We need the pharmaceutical industry and they
need us to deliver improved health care. We have checks and balances.
We make sure that there is no undue pressure by the pharmaceutical
industry on the activities of the MRC but it is potentially a
concern and we watch for it very carefully.
Mr Kumar: For Cancer Research
UK, I would answer the question in a very similar way to the way
that Roberto did. We tend to do two types of clinical trials.
We develop new drugs that arise out of the research that Cancer
Research UK funds, whether in its own institutes or universities
around the country. Sometimes those give rise to new drug possibilities
and we will carry out internally the early phase studies on those
drugs prior to partnering them with a biotech or a pharmaceutical
company. In those cases, all of our studies are entirely controlled
by us with no influence from pharmaceutical companies at all.
We also do a number of later phase studies and those span every
possible type of study you might think of, from the types of things
that Roberto was talking about to does broccoli help you avoid
bowel cancer, to new studies on drugs either prior to or post
registration. In the cases where we are looking at those types
of trials, we will always insist that we control the protocol
and the study design. To the extent that a pharmaceutical company
is involved at all, it would only be to give a sum of money in
the form of an educational grant which would simply be for funding
data monitors or the supply of a drug. It would not be to have
any control over the trial at all.
Dr Boyce: We contract a lot of
trials for the industry but I cannot name a single instance where
they have tried to influence the procedures and the results. They
might argue about the interpretation but that is not unusual even
amongst academics. If there is a breakdown of trust between the
pharmaceutical industry and society, that surely must stem from
the breakdown of trust about science rather than the industry
alone. I do not think the industry has a patent on lack of trust.
That largely stems from the lack of grasp of understanding of
the general public. At least that is the way I see it. We can
produce evidence that something is not useful but it does not
prevent people going on doing it. I wonder how many people in
this room took their vitamins this morning. All the evidence is
that they are not useful but if you believe published data there
will be several people in this room who have taken vitamins. A
well informed public is not taking any notice of scientific facts.
The trust surely has to start with education rather than the pharmaceutical
industry. I think it is a bit unfair to blame the pharmaceutical
industry for lack of trust over science.
Q481 Dr Naysmith: Sir Richard Sykes
was giving the answer to your vitamin thing. There may be a tiny
proportion of the population who will benefit but Sir Richard
Sykes was saying that very shortly you will be able to identify
the relatively small number who want a particular vitamin and
make sure they have it. That will be the end of the vitamin industry.
Dr Boyce: That is a lovely concept
but I fear that Sir Richard is incorrect.
Q482 Dr Naysmith: Have you come across
ghost writing of papers?
Dr Boyce: I have in the pharmaceutical
industry, yes. Once or twice I have been asked to do it but they
have been multicentre studies throughout the world that I have
organised and set up.
Q483 Dr Naysmith: You must have lots
of people who—
Dr Boyce: The problem with academics
is, despite the fact that they need publication for their success
within academia, they are not always good at writing up the publications
and they do not always write well.
Q484 Dr Naysmith: Do you write for
them?
Dr Boyce: No, I have never done
it, but I have known individuals within a pharmaceutical company
write up a publication in which the company was involved. Always,
the clinicians who do the study are involved and they have a say
in interpretation. If they do not like the conclusions, that is
because they have not spoken up.
Q485 Mr Burns: When they have been
ghost written, from your experience, does it say anywhere in the
document it has been ghost written?
Dr Boyce: We have to define what
you mean by "ghost written". Many professors put their
name on the end of a paper written within their own department
and they may have very little input into that study.
Q486 Dr Naysmith: In my experience
they always say, "The original idea was mine."
Dr Boyce: Yes. You could argue
that the paper has been ghost written for the professor. The difficult
bit is getting a blank sheet of paper into a first draft. Lots
of people can do that but the honing and shaping requires input
from everybody. Providing the clinicians, the sponsors and everybody
has two pennyworth, I do not have any strong feelings about who
writes the first draft but I do not call that ghost writing. Some
people are better motivated than others at writing up papers.
Q487 Mr Burns: I recognise that people
are very busy but in the non-academic world if a politician, for
example, writes his memoirs and they are ghost written it usually
says, "Fred Bloggs with Joe Smith." People understand
that it is not Fred Bloggs who has written from word one to the
last word at the end of the book. If there is a professor who
is an acknowledged expert in a particular field of research and
his name is put on the document, it will be put on the document
for one particular purpose, which is it will seek to give credence
to the content of that document because that individual has a
reputation for expertise in that field. If that individual has
done no work on writing the document and it is the work of others,
is that not somewhat misleading and very disingenuous?
Dr Boyce: Yes, I agree entirely.
There are rules about publication and authorship. In that instance
you have just cited, it would be quite wrong of that opinion leader,
which is the term people in the industry use for someone that
is well known and influences prescribing habits, to allow his
name to go onto the paper.
Q488 Dr Taylor: Mr Kumar, I was pleased
to hear you say that if Cancer Research UK are taking part in
a combined study with industry you control the study and the design.
You insist on publication?
Mr Kumar: We do, of every trial
we fund.
Q489 Dr Taylor: And the MRC?
Dr Solari: I believe it is the
case for the MRC as well.
Q490 Dr Taylor: I was very intrigued
with Dr Boyce's suggestion that a condition of ethical approval
should be that results are published. Is that a feasible condition
to put on? Is it practicable?
Dr Boyce: I believe it is, yes.
It is also a requirement of the Declaration of Helsinki, the 2000
version, which has not been recognised under the EU Directive
but I think it could be. It is in many protocols. It is also a
requirement of good clinical practice that there be within the
protocol a statement about publication. If I write the protocol,
I always put "if the results merit." Sometimes, despite
the fact that they are negative, if you are just doing a single
dose rising study to assess tolerability, there is nothing of
any scientific value in the study and nobody is really interested
in publishing it. It is not hiding it; it just does not merit
publication. Maybe when you start to get a randomised trial, which
was mentioned by one of the speakers this morning, then obviously
I agree it should be published.
Q491 Dr Taylor: That sort of very
early study probably would not have ethical approval.
Dr Boyce: It would. Every clinical
trial has to have ethical approval.
Q492 Dr Taylor: I thought those were
before you got on to the stage of clinical trials.
Dr Boyce: Under the EU Directive,
since 1 May this year, every clinical trial and investigation
of a medicinal product, of a potential new medicine, must now
have approval of the MHRA and the Research Ethics Committee.
Q493 Dr Taylor: It would seem to
me to be a very simple, straightforward recommendation for us.
Dr Boyce: Yes. There should be
a statement in every protocol. That is good clinical practice.
Several years ago I wrote a publication policy for our own company
along those lines. Sometimes the pharmaceutical companies are
a bit naughty. We do the work but they go off and publish it.
They do not tell us. Sometimes they give us recognition but they
do not include us amongst the authors. Under the new rules of
authorship, that is probably okay but it is very discourteous
to publish something that somebody else has done and not tell
them. Usually when we publish there is good collaboration. We
discuss the paper. We have different interpretations. We come
to an agreement about the wording. In the early stages, it is
researched. It is in nobody's interests to distort the results
in early studies. Everybody wants to know: is this a useful medicine?
Does it need to go into late development? If not, it needs to
be put in the bin and another one tried.
Q494 Dr Naysmith: When I talk about
negative results, it is when you do three or four trials and most
of them are negative but one shows up as positive. You then suppress
the four or five and use the one that shows that your drug is
accurate.
Dr Boyce: That is quite wrong.
Q495 Mrs Calton: It seems to me that
there is room here for a grey area around the decision not to
publish trial results or parts of them. Who makes the decision?
Dr Boyce: For the research that
I do, we make it as a group. Often I say, "This is a very
interesting result. It adds to the literature. We should publish
it." Nowadays, somebody else writes the first draft. I never
allow my name to go on a publication unless I have had a substantial
input into it. Until recent years, I always seemed to be the fall
guy who wrote the first draft and took it through because I enjoy
doing that. There is nothing better than doing a study with a
brand new molecule and getting a very interesting result that
is going to set the development in process. The decision is usually
made amongst the group, as in academia.
Q496 Mrs Calton: Can you tell me
who the members of that group would be?
Dr Boyce: It would be the clinical
pharmacologist doing the trial and representatives within the
pharmaceutical company.
Q497 Mrs Calton: Would they ever
say, "We do not think this should go forward"?
Dr Boyce: They may, yes. I have
cited examples where it has happened to me, where I have said,
"I would like to publish this. It is in the protocol. It
says, `if the results merit'" which is usually my phrase.
Then either the sponsor or us, the investigators, will write the
first draft and send it to all the other individuals involved
in carrying out the trial to comment in order to hone and polish
the final paper. It is a group of people but occasionally when
I have initiated that process the pharmaceutical industry says
no. That has happened to me and I have always battled against
it. I could give you examples. Once, when I worked in a pharmaceutical
company—this is going back 20 years—when I wanted
to publish something, I had agreement with academics. They said,
"Will we be able to publish this?" I said, "Yes"
and I put that in the protocol. It went through a protocol review
process so the people in the company had seen it. I was not doing
things on my own. When we wanted to publish it, we wrote the first
draft and I submitted it to the company for comments. They said,
"No, you cannot publish it." I said, "But you said
earlier on I could" and I was threatened with a High Court
injunction if I went ahead to do it. Unfortunately the academics
backed off, not me. I was in the company. I was left very vulnerable
for a period. It was published a year later. A lot of the time
it is a storm in a teacup. There is not the need for secrecy in
the early clinical development. Once a new molecule goes into
studies in humans, it does not go into humans until it is patented
and protected. Then you have to produce an information leaflet
for the subject. Aunt Mabel would know about it and the man in
the street might be a volunteer. Why should it not be published?
There seems little point in holding back.
Q498 Mrs Calton: Effectively, from
what you are saying, the sponsoring company that clearly has an
interest might well block publication?
Dr Boyce: Yes, often for the wrong
reasons.
Q499 Mrs Calton: Whatever the reasons,
the point is the public and those who are buying the drug subsequently—
Dr Boyce: This may be 10 years
away from becoming a product that is sold to the public. The attrition
rate is very high.
Mr Kumar: I think there is a relatively
simple way of overcoming the greyness that you describe which
is if that drug ever does make it to market, regardless of what
the reasons were for not publishing when the early phase studies
were done, whether it did not merit or commercially in confidence,
as and when a drug hits the market all data should be published.
That way you overcome any greyness that there might have been
through the process.
| 
