THURSDAY 14 OCTOBER 2004

MR RICHARD BROOK, PROFESSOR DAVID HEALY AND PROFESSOR ANDREW HERXHEIMER

  Q160  Mr Burns: Have you been in the Caribbean in the last fifteen years?

  Professor Healy: To be honest with you, I have not. I have actually only once been in the Caribbean; so in the last fifteen years once—twice actually.

  Q161  Mr Burns: Why did you go?

  Professor Healy: I went to the Caribbean to try to interview people who were involved in the history of the field.

  Q162  Mr Amess: Turning now to Mr Brook, and I belive you did touch on this earlier, you resigned in protest from the Drug Regulatory Committee examining the safety of certain anti-depressant drugs. I wonder if in a moment you could enlarge on that a little? From your experience what can you tell us about the unwelcome or undue industry influence and the regulator's ability to actually contain it? Do you have any recommendations for this Committee as to how it can all be addressed?

  Mr Brook: I will try and answer all those. I just want to say, because I think perhaps it was not clear, we are very concerned, I am personally very concerned, about the drug regulatory system. It does not make us anti -drug, and I think that is very important to understand. If you read Mind's information leaflets they talk about the positive use of drugs within mental health, but the issue I think that we have, and I think my experience is raised, is have we got a regulator that is robust and trustworthy, because at the end of the day both GPs and patients are relying on the information that comes out of the regulator? I do not think we can expect an industry making huge amounts of profit necessarily to be effective at self-regulation in these areas. For us it is very important that the MHRA is regulated very strongly, and it is very important to recognise that over a decade or more in this area we have had people saying to us that they have concern about the information they have; and, of course, some years ago Mind was involved in the same issue around drugs like Vallium with That's Life, which most people recall; so there is a long history here. My experience within the MHRA, I think, was quite scary to some extent and quite a painful process: because I joined that committee as a result of a street protest outside the MHRA. I was rung up and they said, "Would you like to join our committee?" On the week I said "Yes" it was on the front of the papers about how I would bring the patients' dimension and the patients' perspective to it. In the first meeting I had the Director of post-licensing came up to me and said, "We are so grateful that you have not had medicine contributions, we are so grateful that you are here because we are not sure that people like you could actually make a contribution to such a committee", and I was not quite sure what that actually meant, but it did not seem very affirming or confirming, but I carried on. I think what really worried me was not so much the direct pharmaceutical influence, although it was fair to say that every time we made difficult decisions there was always this issue of: "We have got to be very careful because the pharmaceutical companies will sue us if we get this wrong; they will take us to court and take us through legal processes"; and it was very clear that the MRHA officials were very mindful of the whole time of that dimension, to my view, more than the dimension of public health and public responsibility of the public. For instance, they would talk about Seroxat having 34 generic manufacturers and potentially each one of those generic manufacturers could lead to legal action against them if they got it wrong. So it was hugely big in their thoughts. I think the second thing that actually worried me was when we actually got to things that looked really quite worrying, and I have mentioned Seroxat, and I also mention venlafaxine or effexor, as it is sometimes alternatively known. In both cases the information came late to the MRHA, in my view, two years after the trial had finished, and in both cases it was not seen as hugely important, and I seemed to be the lone voice on this expert committee saying, "This is of concern", and the response I would get is from the Chairman or the officials, "Yes, this is very worrying, but it is going to have to be formally investigated", and it seemed to go, in my view, into a black hole and remains there to this day despite questions on the floor of the House and questions elsewhere. It seems to me that even in a criminal investigation situation such as, say, the worst case of murder, we actually get more information than we do about how drugs are regulated. The other problem I have with it, if I am really honest—I know this is a long answer and I will try and bring it to an end—is actually it is a very difficult thing to be confident about the transparency of the regulator when so many people have got long histories, career histories, in the pharmaceutical company. Let me give you some examples without trying to be too personal, but, again, I have data and files which I am happy to provide to you to back up what I am saying. The head of licensing at the MHRA, the current head, had a previous major role in GlaxoSmithKline on the safety of drugs across the whole world; the head of enforcement had a 20-year career with GlaxoSmithKline before he became head of enforcement; and recently Professor Breckenridge at a fringe meeting, actually the Conservative Party fringe meeting Mind held, said that basically it was a requirement for the head of enforcement to have five years close involvement in the industry as part of their job description. I cannot understand why enforcement needs to actually have that experience. I can understand why an enforcement agency might need that. It also seems to me to be very bizarre that you have got your enforcement inside your licensing, inside your pharmacological division, all speaking to each other, all this work going on in the same committees, all of these people with these interests. So for a number of reasons, and there are others I can give as well, I got very confused and very concerned that actually there was no robustness; and when I looked round I was the only patient representative in this whole group taking up these interests.

  Q163  Mr Amess: But what is your solution to all this? We are happy to give therapy and Professor Herxheimer will want to get things off his chest as well, but tell us what you recommend us to do?

  Mr Brook: I think, if you look at Mind's recommendations, it is very, very clear. We want to see a much better way of doing health research and trial data. You have already heard evidence on that. We want to see the licensing and the post-licensing work separated, quite clearly, and we want to see people with a consumer interest and a legal interest coming onto the committees to actually give that moral and ethical dimension.

  Q164  Mr Jones: Mr Brook, can I say, firstly, before I ask you any questions, all witnesses to the committee have parliamentary privilege.

  Mr Brook: I did know that before I mentioned Wyeth.

  Q165  Mr Jones: Just in case you feared?

  Mr Brook: I have no fear from you and what I say here. I do certainly remain still somewhat fearful of the MHRA's approach to me, I must admit.

  Q166  Mr Jones: In the answer to the last question you made clear the reasons why you thought the regulation would not work, but in your written evidence to us you say, "The concept of the Department of Health as a regulator is nonsense. It has no power to regulate the vast majority of pharmaceutical activity." That is not just saying that the way they are brought together means they do not do it; that is saying they have not got any power to do it anyway?

  Mr Brook: Absolutely. On the committee time after time after time the experts said, "We need more work done on this work", and I would say, "How do we get more work done?" and they would say, "That is a real problem. We do not have any funds. We cannot direct the manufacturer to do it. We have said this drug is safe. We are not able to reopen that debate", in effect, and so they get stuck with that; and the DH does not have that ability. Just a little cameo: after the contra-indicating of Effexor the Department of Health official turns up at the meeting, and says, "We are really worried that you are actually contra-indicating all these drugs for children, because people have not got anything to prescribe to them and we have not got any alternatives out there; so what are we going to do about this situation?", and actually I said, "I do not think that is this committee's problem."

  Q167  Mr Jones: But you are going back into why they do not behave that way?

  Mr Brook: Sorry.

  Q168  Mr Jones: I am now trying to ask you the question of, you say they do not have the power, well give them the power?

  Professor Healy: Chairman, could I enter into this? You perhaps thought that the view that I gave earlier to David Amess was somewhat flip when I said the industry are actually doing things quite well if you hold shares in the various different pharmaceutical companies. I am not sure the industry actually are the problem. I think there are two groups, one is the MHRA, who are not doing their job all that well, and the other is the physicians generally. If I can try and bring out the nature of the problem: as regards suicide on SSRIs, both the FDA in the US—and the MHRA—clearly here thought when this issue blew up first that it was a public relations issue. They took this position without any scientific input at all other than the scientific input they may have had from experts sitting on the CSM who we now know had extraordinarily close links with all of the major pharmaceutical companies. They have held to that position regardless of the scientific evidence that has come through over the course of the last ten to fifteen years, they have held to that point of view even though actually the scientific evidence on which they let the drugs onto the market in the first instance conclusively showed that these drugs could cause a hazard, a hazard that could be greatly reduced if the proper warning had been put on the drugs. The other aspect to the MHRA that I would be keen to bring out quickly is that they say the yellow card system they have got is one of the best in the world in terms of trying to track hazards that may be thrown up by drugs out there in the real world, but in actual fact here in the UK we track the fate of parcels through the post one hundred times more accurately than you track the fate of people who have been killed by SSRI or other drugs. If you or your wives or children were to go to your GP and be put on one of these drugs and be injured or killed by these drugs, your GP would not file a yellow card with the MHRA. The system as it stands is worthless. But let us move on. There is a third group here that you have not brought into the frame, and that is the Royal College of Physicians, the Royal College of Psychiatrists. Actually we are supposed to be the expert advocates for the consumers, and from us you have heard complete silence. I am not advocating that all drugs should be over the counter, but if you think of the situation where all drugs were over the counter, where it was as easy for you, the consumer, to get these drugs as it was for you to get pints of Guinness or perhaps tobacco, you would go into your physician and he or she, usually, I would say, she, would say to you, "You do not want to believe all the hype, all the adverts you see on TV for instance about Guinness being good for you", or this, that and the other actually being good for you, "Actually the evidence looks very different to us", but in the kind of situation which we have, which is drugs are available to you through being prescribed by people like me, what the industry have done has been to try to try to capture the hearts and minds of the Royal College of Physicians here in the UK, the APA over in the USA, and we have been quiet. The canary that should have croaked in the mind has not. So there is a third group of players here.

  Q169  Mr Jones: Thank you very much. My next question is to Professor Herxheimer. In your submission, Professor, you state that the close relationship between the industry and the regulatory authority over decades means that the industry's views are better represented than the interests of the patients and the consumers and the public. Would you elaborate on that and explain why the bias? I am sure you echo some of the views that Professor Healy has just expressed.

  Professor Herxheimer: I think that the whole basis of medicine regulation started with Thalidomide, and then there was the Sainsbury Committee and the Medicines Act, and that was very much influenced by the industry, what was to be in the Medicines Act, how strong or weak, etc. The whole confidentiality, the issue of commercial confidentiality, meant that anything submitted by a company to the regulators could not be disclosed under penalty of fines and prison, etc, and that meant that many, many things could be discussed, in the regulatory agency, which were absolutely private; so that was a very privileged position; that led over the years, over the 40 or more years, to a closeness between the regulators and companies that they were often meeting to discuss details of submissions, information to be given on the package insert and the product characteristics, and so on—they became one community—and so, when the agency was hived off from the Department of Health, became independently funded, independent of government funding, was funded by the industry, the culture became confirmed that the industry is the client and the client must be looked after: quick service, good service, easy contact, etc—so it is a closed community in a sense—and outsiders were related to this either by being appointed to one of the committees of the regulators, the Committee on Safety of Medicines and sub-committees, and thereby tied into the culture of secrecy, signing every document as commercially confidential, or whatever; but commercial confidentiality was never defined, so the anxiety, which has been mentioned already, of the regulators, of the civil servants in the agency, that they might be sued by a company for breach of confidentiality—the Department has a horror of being sued by a company for this, and so there have been very few prosecutions by the agency of companies for various misdemeanours. All this has led to this close inbred relationship. I have no idea how social it is. I do not know . . . I am sure they do not go to the Caribbean, but that is at the back of what I wrote.

  Q170  Mr Jones: So the laws representing the Government in these committees are sensitive, understandably sensitive, to pressures from the industry for litigation, but they are not subject to other counterweighted pressures in that, I cannot recall, but I am not as knowledgeable in this field as you are, governments being brought to account because they allowed drugs to be distributed inappropriately?

  Professor Herxheimer: Quite; yes.

  Q171  Mr Jones: Not since possibly Thalidomide, as you have mentioned?

  Professor Herxheimer: Yes. I think one very interesting example which typifies the situation is that companies may appeal against licensing decisions. If licences are refused on a drug the company may appeal, and it is then heard at a formal appeal by the Medicines Commission—that is one of its jobs. No-one else may appeal. The evidence may be as ropey as anything, but nobody else has any standing. A licensing decision can only be appealed by the applicant, not anyone else; and that is absurd because everybody else has to swallow the drug willy- nilly.

  Q172  Dr Taylor: I was going to ask questions about the MHRA, but we have had such universal condemnation, the only question is: should it be abolished and what should be put in its place?

  Professor Healy: There are a few ways you could re-form it. I think one of the key issues that you heard during the first hour, and I think you would hear from all three of us, would be the issue of transparency. It is not the case that the data from clinical trials needs to remain concealed. Let us be clear what happens. You and your wives and your families go to see me when you are ill and you are in a very vulnerable kind of position, and I happen to say, "Ah, good news. We are doing a clinical trial on a new drug this week. Would you not like to get involved?" Partly because you are on your way back to health and because you want to keep me happy, you say, "Yes." You do not know that I would not get involved in the trial because I know that actually three-quarters of the trials prove that these drugs are too hazardous to market but we go ahead with you. What happens is you take these risks you do it out of a civic sense, you do it as a gift to the community. It is part of the spirit that set up the NHS fifty years ago. You do it for free. The industry takes the data from you, they let you take all the risks, they conceal the data; and this is a thing that has really only happened during the last twenty odd years or so, the capacity of the industry to do this is a fairly recent thing. They take this data, they take out the good bits of the data, the bits that suit them, and market that back to us and call it science, when clearly it is not. In the course of doing this they became the most profitable corporations on the planet with the power even to shape human experience. They can create illnesses out of the blue. We may all have been happily impotent until quite recently, but we will have problems with our impotence these days because Viagra persuades us that actually being impotent is not the kind of thing you should be doing, you should be having Viagra. They can change the nature of what it means to be human. One of the ways round this is access to the raw data. There is no scientific or ethical reason why there could not be access to the raw data.

  Q173  Dr Taylor: What about the funding issue?

  Mr Brook: I think we do need an equivalent to the MRHA. I think our concern is how it operates. Clearly there is a lot of evidence. You have already heard evidence from us and previous people about the issues around trial data, etc. There are two dimensions that also need to be considered in your thinking: one is funding, because clearly if you look at ABI's submission to you, and no doubt you will be asking about this, there is a whole expectation that we will remain the best in Europe to attract funding and, as a result of that . Part of that reputation is based on the relationship with pharmaceutical companies; so I think you have a whole funding issue that is driven and no independent ability do much trial data work at all. The second issue I think you have to look at is the European dimension, because, for instance, in Seroxat one of the real dilemmas that people had was that it has got a European licence. It has not got a UK license; it has got a European license. It was often raised, "We cannot do this because we are not going to get support across Europe, and even on the dosage issue that was a real concern in the discussions that were taking place. So a certain number of drugs, an increasing number of drugs, are actually going to be regulated across Europe, and, of course, the work of being a lead rupotevr, as it is called (I am not quite sure why that word is used), actually acquires funds; and so clearly you have got to be in not only with the pharmaceutical companies but actually in terms of how the European regulatory world sees you. So I think you have two issues: one is economic and one is the European dimension, which I think is actually quite pressing.

  Q174  Dr Taylor: What about the membership of the MHRA? Should we be making recommendations on that?

  Mr Brook: Absolutely. I think we have seen in recent times, if you look across health issues which we have been involved in and others have been involved in, such as the Bristol Inquiry, the Alderhay Inquiry, the Lane/Isaacs Inquiry around organ retention, what you have started to see is that when people come in with a moral and ethical dimension to those issues rather than just the medical position , you start to see, I think, policy change, and I think that is perhaps somewhere that I would recommend you might give due thought to about the nature of their composition, and also, of course, I would say, and I would argue strongly, we need to get patient experience in there, because the reality is that, if you look at the experience of the SSRIs, patients have been saying issues that have now been found to be true over the last decade.

  Professor Healy: Could I add into that one, purely on the issue about who is in there? In terms of the experts, just to point the issues to you, some years ago I wrote a piece. It was known to one of the pharmaceutical companies that I had an article that was due out that was going to be critical of one of their drugs; it was going to lead to the SSRI review on which Richard ultimately ended up, but before the SSRI review that Richard was on there was a previous SSRI review group—and I am trading on the fact that things are privileged here. If you go into the archives of the particular company concerned, I can find there that will be e-mails from the company to journal editors here in the UK and Europe, etc, etc, saying, "Look, there could be this article coming out", and broadly hinting at, "You know how to handle it. This is not kind of material you would want actually to publish." If you look at who the e-mails go to, you end up with what in essence was the first SSRI review committee here that the MHRA set up. This is extraordinary. You can also find material which shows that the companies clearly get key figures from within the UK and France and Germany and note these as figures who have links to the regulatory apparatus in each of their countries. They are doing this regardless of the culture in England, Germany and France which has been quite different. The culture in England, there has been some free interchange between experts on groups like the CSM and the industry. In Germany this has not been the case, but the industry has been able to capture the regulatory system there also. It is a fairly systematic process.

  Q175  Dr Taylor: Do you think the MHRA can reform themselves in any way: because if you saw the Panorama program I do not think I have ever seen anybody more uncomfortable than the MHRA representative being grilled on that?

  Professor Healy: Richard, I am sure, is absolutely right that there should be more consumer input into MHRA, and there should not be just one consumer input, but you would have to take care that the consumer is not from a group that has, in effect, been set up by the pharmaceutical companies. Also there is great scope here for experts to be on the MRHA committee who do not have links to the industry. The issues involved of what do clinical trials show, what do the statistics show, which MHRA and their experts have got consistently wrong in the case of the SSRIs, are issues that we have loads of other experts here in the UK who do not have links to the industry who could handle—

  Mr Brook: I am sorry. I think it is only my observation, but certainly the committee I was on for people that were most open-minded were the statistician and the academic, and if I had any support it came from that sort of quarter rather than from the medical area. I just wanted to say a little bit about reform. I think it needs a whole new mindset, a major mindset. I was appalled, for instance, because I raised several times the issues around freedom of information and how the Freedom of Information Act will impact on the MHRA sitting on the expert group, and I have read recently that they have actually set up a group that involves the ABPI in themselves to decide what to do about it, and recently, at a fringe meeting again, I made the point, which was not answered, about why are there not patient representatives and why are there not lawyers, why are there not people from Which? sitting on this group? It is just so close, so cosy, you have got to break that mindset.

  Q176  Dr Taylor: Can I go back to Professor Healy. How many clinical trials are not funded by the industry?

  Professor Healy: Very, very few, and this is quite odd in a sense, that within the NHS you would have thought we would be running clinical trials that are not funded by the industry; but one of the colleagues that I worked with looked at this recently, and in the US, which operates a much more privatised system, you have much more state-funded clinical trials than we have here in the UK. There are virtually no state-funded clinical trials here in the UK. This is probably very, very important. It is a point that I mentioned earlier. The MHRA are really a very, very small group of people; they are not the experts on what these drugs do or whether it is good for you to have these drugs, or how this drug compares with other drugs in the field; they are really a very small group of people who probably have been given undue salience here. The expertise lies in the Royal College of Physicians or the Royal College of Psychiatrists, or whoever. You really need experts out there who know what these drugs do and who are able to create the political context in which MHRA will respond. If MHRA know the Royal College of Physicians out there have concerns about a pill, they will be much freer to ignore the worries they may have about being sued by the industry than if there is no standard at all from the Royal College of Physicians.

  Q177  Dr Taylor: Going back to the yellow card system, what should we be recommending for reforms of that?

  Professor Healy: Consumers ought to be filling this up: the work that has been done by Andrew Herxheimer and Charles Medawar on this shows that you get much more information from consumers filling these up. What you might also get if you had that kind of situation, you may also get physicians being more prepared to fill the cards up also and in a more detailed way than they are now.

  Q178  Chairman: That is a good question. Professor Healy, a few moments ago you used, in the context of Germany, the term that the regulatory mechanism had been captured there by the industry. You implied, and I want to be sure I understand this, that it had been captured also in this country. Did I understand you correctly?

  Professor Healy: Yes. I think one of the things that sociologists in this field have been working on recently is what are called "regulatory capture", and they mean just that.

  Q179  Chairman: You say that applies within the UK?

  Professor Healy: As regards the area that I work in, the field of both anti-depressant drugs and the drugs that are used to treat people with schizophrenia, I think that has been the case since the late Eighties at least.