Examination of Witnesses (Questions 100
- 119)
THURSDAY 14 OCTOBER 2004
DR DES
SPENCE, MR
GRAHAM VIDLER,
DR IKE
IHEANACHO DR
PETER WILMSHURST
Q100 Dr Naysmith: So how do we achieve
the switch? Do patients like the talk therapies better than being
given pills and shoved out the door?
Dr Spence: I do not know how you
do that, but it goes back to what this general argument and discussion
is about, which is looking at the current relationship between
the industry, health care professionals and government as a whole.
It is that close relationship that gives them an undue sway over
the health agenda.
Q101 John Austin: This is a question
for Dr Iheanacho and Mr Vidler. In your evidence you have actually
said "a weak and unco-ordinated regulatory system is enabling
the pharmaceutical industry to further its own interests without
sufficient regard to public health." That is a fairly damning
indictment. What do you mean by "a weak and unco-ordinated
regulatory system"?
Mr Vidler: We noted in our evidence
two specific examples, one of which was around the reclassification
process, where our concern is that the process is being driven
by targets imposed by government, so that the assumption is that
a reclassification is a good thing in its own right because the
government believes that more people should have access to medicines
over the counter and more people should take control of their
own treatment. What this leads to is a situation where drugs are
being reclassified without due consideration given to whether
or not they are actually bringing public health benefits. We have
a situation where drugs are reclassified and there are clear benefits
for the company whose drug it is in terms of profits, but the
benefits to the public are much less clear. The most recent high-profile
example is the statin Zocor, where we know that the drug works
at a particular dose for high-risk patients. To speed up the reclassification
process, it is being allowed to be sold over the counter at a
lower dose and to patients at lower risk. We simply do not know
if it will be effective for that group, but what that group is
being asked to do is spend £13 a month to participate in
a clinical trial, to see if the product works in those conditions.
That was the first key area we flagged up: reclassifications.
It might be better if Ike spoke about advertising and promotion.
Dr Iheanacho: From the experience
of Drug and Therapeutics Bulletin, the clearest example of weak
regulation comes in the promotion of prescription-only medicines.
A large part of our workload is assessing new medicines, and in
the course of that we occasionally look at the advertising that
accompanies those medicines. Our experience, which echoes that
of others, is that often those products are promoted misleadingly.
There is something in the regulatory system that allows that to
happen, and it is worrying.
Q102 John Austin: Can I ask you as
well about the monitoring of side effects and adverse reactions,
and whether the regulatory control there is sufficient? In some
of the evidence we received which referred to the early detection
of safety hazards, there is the use of the black triangle labelling
that doctors; nurses and other medical staff are then asked to
record adverse reactions to those medicines. My understanding
is that that is a voluntary system, not mandatory. Does it work
as a voluntary system?
Dr Iheanacho: If you mean does
it identify every adverse reaction it should do, the answer to
that is no. The system is voluntary from two aspects really. It
is voluntary in the sense that it relies on companies to put the
triangles on all of their products. In the past, from our own
work, we know that two or three years ago that was a problem,
because we identified several cases where companies, for whatever
reason, had not been doing that. I think that has been tightened
up now, so you can expect a new product which should have a black
triangle on it to have it.
Q103 Dr Naysmith: Is it mandatory
on the drug companies to notify the MHRA if there is a potential
. . .
Dr Iheanacho: Absolutely. It is
mandatory for drug companies but it is not mandatory for health
care professionals. If you are a doctor and you are told about
an adverse reaction by your patient, it relies on you to fill
in a yellow card and submit that to the Committee on the Safety
of Medicines. That is voluntary.
Q104 Chairman: Can you explain to
us why it is voluntary? It does seem rather odd.
Dr Iheanacho: That is a good question.
It is not voluntary everywhere. It is not voluntary throughout
the world. I cannot answer for it. It is not my policy. I think
at the time it came about there must have been a genuine feeling
that doctors would report adverse reactions, would be keen to
submit to a system which would collect all these data and make
them available for future prescribers and eventually patients.
Do not forget that a lot of this grew up in the wake of the thalidomide
scandal in the Sixties, and at that time I guess there was a genuine
feeling that if this kind of thing could happen again, people
would be very keen to report adverse reactions but the reality
is that often it does not happen, I suspect for a number of reasons:
there are other things to do, doctors are busy.
Q105 John Austin: Has it worked,
for example, with Seroxat? There has been a lot of concern about
side effects.
Dr Iheanacho: I think witnesses
after us will give you a lot more background to what has happened
in terms of that, but the short answer is there has been a problem
with yellow cards in relation to Seroxat in terms of how that
information was collected and dealt with by the regulator and
made available to people who might be in a position to prescribe
the drug. So yes, there has been a problem with that particular
drug, but others can say a lot more about that.
Q106 John Austin: Do you or the CA
have a view as to how the public interest may be better served
by a different regulatory system?
Dr Iheanacho: I think ultimately
it is difficult to get away from the idea that, difficult though
it may be, the best person to tell you about an adverse reaction
is the person who is suffering it. That raises a lot of problems
for regulators because they say "It is very difficult; patients
will not be able to understand what a serious effect is, or what
a minor effect is; it is going to produce a lot of data; there
will be a lot of noise in the system"; but ultimately, if
you want a pure account of what happened and you want to be able
to tie that to the taking of a particular medication, the best
person to tell you that is the patient. If you rely on a third
party to tell you that, diligent though he or she may be, you
start to erode some of the experience. In fact, you may not get
the experience if you rely totally on the yellow card system.
Q107 John Austin: Dr Iheanacho has
just told us that it is mandatory on the part of the drug companies
to report all adverse drug-related events to the MHRA. You have
just indicated in a fairly stark statement that there were inducements
to you to not publish certain information, but in your evidence
you have actually suggested that drug companies knowingly submit
fraudulent material when negotiating with the regulatory authorities.
Would you like to comment further on that.
Dr Wilmshurst: I have documented
in publications the fact that, for example, in the case that I
was involved in, the drug amrinone, when I published a paper on
the side effects of the drug in the British Medical Journal,
I was contacted by a regulator in the Netherlands, the Netherlands
Committee for the Evaluation of Medicines, who pointed out that
he did not understand our paper because on our clinical record
cards the side effects were not reported. I had a copy of my clinical
record cards, and the documents he had were a forgery from the
company. The company had altered our clinical record cards, omitting
side effects. I have also published an example where the same
company got at the New England Journal of Medicine to try to suppress
a publication from Stanley Rubin and colleagues in Los Angeles
about the side effects of amrinone. So there are lots of examples
where that occurs.
Q108 John Austin: How commonplace
would you think it is now?
Dr Wilmshurst: I suspect it as
common now as it ever was, and I think it was very common. In
my experience, there were a number of people influenced by the
company to withhold data in one way or another. Sometimes they
withheld data because they were influenced by opinion leaders
within the profession, who were paid consultants to the company
who went along and spoke to them and persuaded them not to publish.
They told them their data was aberrant and we were told by a very
eminent professor of cardiology that our results were aberrant,
it would be very embarrassing for us when we published. We went
ahead and published and I presented data at the American Heart
Association, and when I did, three professors of cardiology contacted
me, came up to me and said, "We got data like yours but the
company persuaded us not to publish." They got opinion leaders
in, who were well paid to persuade them not to publish.
Q109 Dr Naysmith: I wonder if we
could return for a moment to Mr Vidler and Dr Iheanacho and the
reclassification of drugs from prescription-only medicines to
other categories. You were suggesting that this might lead to
safety problems, and we have probably dealt with this a bit, but
is it possible, do you think, that this can mean that not very
effective medicines or even ineffective medicines get much wider
circulation and promotion? Really, what I am saying is, in the
reclassification process, should there be an attempt to look at
whether the medicines are effective or not?
Dr Iheanacho: Yes. As things stand
at the moment, that is specifically excluded by law from the process
of reclassification if you are seeking reclassification of a product
for a use which is identical to the use that it previously had
as a prescription-only product. If you want your drug to be reclassified
for disease X as an over-the-counter drug—exactly the same
disease, exactly the same patient categories—the evaluation
process does not ask the question "Is it effective?"
because the assumption is that, if the drug has a licence and
has been relicensed repeatedly, one can take it as read that it
is effective in the indication which is being proposed. The only
way to refuse a reclassification is if you think that use of the
drug in the way that is proposed in the new use raises safety
concerns. That might be a reason for refusing reclassification
but you cannot refuse reclassification on the basis of efficacy
at that stage. The only way you would be able to stop a drug being
reclassified is if somebody during the relicensing process, which
should happen every five years, says for example,"Hold on
a minute. We have had this drug for 10 years now. Look at all
the data. Actually, on the whole, it doesn't look that effective.
Why has it got a licence?" That does not happen all that
often.
Q110 Dr Naysmith: Presumably, you
would expect it to be less effective than other drugs on the market
being sold on prescription because one assumes that there will
be better products coming along and they will be the ones which
have their patents still in existence, and almost by definition
these drugs should be less effective.
Dr Iheanacho: Possibly. One has
to be careful about tarring the whole of the OTC market as being
ineffective. That is clearly not true. There are many drugs which
are available over the counter which do bring great benefits to
patients, but to go back to your specific question, could the
reclassification process as it stands lead to ineffective or less
effective medicines being promoted to patients without their knowing,
yes is the answer.
Q111 Dr Naysmith: Do you agree, Mr
Vidler?
Mr Vidler: Entirely, yes.
Q112 Dr Naysmith: What can we do
about it? What should we do about it? At that stage it would not
be sensible, would it, to ask for efficacy tests on these medicines
all over again medicines?
Dr Iheanacho: As the system stands
at the moment, that could not happen. It would need a fundamental
change in the way that we think about reclassification, or the
way the regulator thinks about reclassification. The only mechanism
at the moment is greater critical analysis of in the relicensing
process, so that when a drug comes up for relicensing, to ask
the question again "Does it still deserve its licence?"
which should happen; that is part of the system.
Q113 Dr Naysmith: It is meant to
happen now, but it does not?
Dr Iheanacho: It does happen,
in inverted commas, but you see very few drugs actually having
their licences revoked on the grounds of efficacy, I suppose partly
because if the regulator has taken a decision that something is
effective, there must be an in-built inertia about saying, "Actually,
having looked at all the data again and new data that have come
along, it doesn't deserve it." The other thing to bear in
mind is that when a new drug is licensed, there is a lot of evidence
saying how effective it is and that it deserves a licence, and
so on. The minute it gets its licence, that research work often
dries up completely, because there is maybe no benefit for the
industry, the particular company involved, in publishing new research
once it has its licence. It may actually be the case that there
are no new efficacy data, so for the regulator to say, "Actually,
in the round we think that wasn't a good decision the first time
and we will revoke the licence" is unlikely to happen very
often.
Q114 Dr Taylor: I suspect I am being
rather naïve really, but I thought that gradually, over the
years, we were getting rid of the ineffective drugs. Looking back,
we got rid of expectorants long ago, we largely got rid of the
appetite suppressants that do not work, we got rid of excess vitamins.
What are the ineffective drugs that you are talking about that
are still marketed extensively?
Dr Iheanacho: Perhaps it would
help to give a specific example. I suppose the most prominent
example of a drug which has undergone reclassification which I
do not think has yet come to the market but soon will, is a drug
called Hyoscine or Buscopan, which is a treatment for a condition
known as irritable bowel syndrome, and in particular, relief of
spasm in irritable bowel syndrome. If you want an example of a
drug which is ineffective, or at least appears to be ineffective
for the reason its reclassification is being proposed, that is
a very good example.
Q115 Dr Naysmith: I want to talk
about the Pharmaceutical Industry Competitiveness Task Force,
PICTF. Both of you have submitted evidence to do with the industry,
government, the Prime Minister's involvement, and there is a big
70-page document where the Task Force set out lots of proposals
to try and improve the competitiveness of the drug industry in
this country. I do not want to go into all the details of it,
but since lots of you have mentioned it in your evidence, (a)
do you think it is working and (b) is it working to the benefit
of patients and health care in this country, or is the benefit
totally to pharmaceutical firms?
Dr Iheanacho: I think it is working
in the terms that it is meant to work, which essentially is to
promote the business interests of industry, which is a perfectly
legitimate thing for government to be interested in. If you look
at the reports produced annually and you see the targets which
are set and measure up whether they are being met, in those terms
it is a very successful collaborative. With most of the targets
that PICTF sets itself, it is much clearer to see what the benefits
are for industry than they necessarily are for patients. I am
not saying that it is a wholly useless collaborative that cannot
possibly do any good, but when you read the documents, when you
see how the collaborative works, you sometimes have the feeling,
"Well, OK, I can see why they are doing this. It is a big
industry, it pays a lot of tax, it is very important, it does
a lot of research. These things are all very important, but actually,
what is the spin-off going to be for patients in the long term?"
Q116 Dr Naysmith: Do you think the
Department of Health and the Government should play a stronger
part in trying to decide what the industry does in terms of benefits
to patients and the population in general?
Mr Vidler: Certainly, yes. We
quite understand the Government's desire to have a competitive
pharmaceutical industry contributing to the economy and contributing
to employment, but that needs to be in second place to public
health benefits. As Ike was saying, PICTF does a good job in its
own terms. Where is the public health balance to that, and is
it strong enough? Those are the questions we are asking.
Q117 Mr Amess: I am going to ask
you a couple of straightforward questions. Gentlemen, do you welcome
the influence of the industry in the promotion of newer drugs?
The other point that I wanted to raise with you: how corrupted
are doctors by the pharmaceutical industry in the promotion of
these new products? Here we have a witness telling us all about
free lunches. If these free lunches are as rife as perhaps you
are going to share with us, it is not going to do this Committee's
campaign on obesity much good, is it?
Dr Spence: I can only give you
a personal perspective of 10 years' experience. I can tell you
that I know hundreds of doctors and I know what the industry is
like on the ground. The industry on the ground is unbelievably
vociferous and active in promoting its own message, and there
is a widespread hospitality culture in medicine. Whether the profession
want to accept that or not is open to debate. The amount of hospitality
received by the medical profession compared to other public services
is, in my view, a complete disgrace. If you had other public servants,
like civil servants or teachers or policemen, receiving that level
of hospitality, there would be a public outcry. There is this
idea that doctors are somehow different from other people, that
we are anointed by God and made of a different moral fibre. That
simply is not true. Doctors share the same failings as the rest
of humanity. They are just representative of society as a whole.
You cannot blame doctors, because this is what they have been
used to. I always say talking about these things is rather like
playing Father Christmas. "Oh, Father Christmas, you gave
me too many presents this year!" It is that sort of relationship.
That is what we are going to move away from. That is why it is
difficult for doctors to hear this. It is so ingrained in them
that they do not see it as being a problem, but it is a problem
because it affects directly the medicines and health care that
is delivered to patients in this country, and we have a professional
and moral obligation to protect them.
Dr Wilmshurst: I think there are
the issues around the influence on doctors, but there is also
a more important influence, and that is the influence on government.
When I did work with amrinone years ago, the fact is that we discovered
we had been lied to about the clinical trial certificate. There
was no clinical trial certificate for the oral drug, and we had
conducted trials at St Thomas's and others at the National Heart
Hospital, Hillingdon Hospital, the Freeman in Newcastle and in
Birmingham.
Q118 Mr Amess: Who lied to you?
Dr Wilmshurst: The pharmaceutical
company. They told us they had a clinical trial certificate for
the drug, and we conducted trials, and when we discovered that
there was no clinical trial certificate, we went back to the Medicine
Control Agency, or CSM, as I think it was called then, and they
conceded that there was no clinical trial certificate, but the
senior vice president of the company, Dr Trout, came over from
America and said that the company would not be prosecuted for
the breach of the Medicines Act—a serious breach—because
he was going to tell the Health Minister that if they were prosecuted,
they would shut down all manufacturing of drugs in this country,
which would include their large manufacturing plant near Newcastle
Upon Tyne. The company was not prosecuted although there was a
clear breach of the Medicines Act.
Q119 Mr Amess: When was this?
Dr Wilmshurst: This was in the
mid-Eighties.
Mr Amess: I will not question you any
further on this point. You had me mildly interested if it was
since 1997.
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