House of COMMONS
MINUTES OF EVIDENCE
Thursday 14 October 2004
DR DES SPENCE, MR GRAHAM VIDLER, DR IKE IHEANACHO and DR PETER WILMSHURST
USE OF THE TRANSCRIPT
Taken before the Health Committee
on Thursday 14 October 2004
Mr David Hinchliffe, in the Chair
Mr David Amess
Mr Simon Burns
Mrs Patsy Calton
Dr Doug Naysmith
Mr Jon Owen Jones
Dr Richard Taylor
Memoranda submitted by No Free Lunch and the Consumers' Association
Examination of Witnesses
Witnesses: Dr Des Spence, UK Spokesperson, No Free Lunch; Mr Graham Vidler, Head of Policy, Consumers' Association; Dr Ike Iheanacho, Editor, Drug and Therapeutics Bulletin; and Dr Peter Wilmshurst, Consultant Cardiologist, Royal Shrewsbury Hospital, examined.
Q87 Chairman: Can I welcome our witnesses to this session of the Committee and express our thanks for your written evidence and your willingness to come and speak to us today. Could I ask you briefly to introduce yourselves to the Committee.
Dr Wilmshurst: I am Peter Wilmshurst. I am a consultant cardiologist at the Royal Shrewsbury Hospital.
Dr Iheanacho: My name is Ike Iheanacho. I am Editor of Drug and Therapeutics Bulletin, which is published by Which?
Mr Vidler: I am Graham Vidler, Head of Policy at Which? For the sake of clarity, I should explain to the Committee that since we submitted written evidence, we have changed the name we campaign under from "Consumers' Association" to "Which?"
Dr Spence: I am Dr Des Spence. I am a GP, and I speak for the No Free Lunch organisation in the UK.
Q88 Chairman: Can I begin by asking a broad, general question, probably to you, Dr Spence, and some of the other witnesses, as to how you feel our approach to health care in this country is shaped by the role of the pharmaceutical industry.
Dr Spence: We certainly feel that the industry has a major influence over health care policy and that the influence of the industry is across the board, so it is not just a question of impacting upon doctors and nurses but it is the involvement with patient organisations and with government agencies. The industry is active in all these spheres and has a very clear agenda. Our perspective is that the agenda of the industry, which is predominantly that of profit - and they are responsible to their shareholders - is in some ways in direct conflict with the responsibilities of the NHS.
Q89 Chairman: If I were to put it to you in a different way, if we did not have the industry working as it currently does and as you and the other witnesses have described, and the influence it has, which comes over pretty clearly in your evidence, how might our approach to health care be shaped differently? Would we do things differently to the way we do them now?
Dr Spence: We probably have different priorities, in the sense that if you have an industry that is worth £9 billion a year, that has enormous clout over the priority setting. We certainly feel that health care is not merely about drugs. Health is not about what medications you take. It is a much broader brush than that. We would seek a much broader discussion about health in its global sense. One of the issues that I feel very strongly about as a day-to-day general practitioner is the amount of health anxiety and health neurosis that has been generated, often through things like disease awareness campaigns. We certainly feel that is undermining people's sense of health and wellbeing. To put it bluntly, the reason for that is because it is in the commercial interests of the pharmaceutical industry to promote new conditions and different conditions.
Q90 Chairman: Can you give any specific examples? What you are saying is people are being made anxious about a condition, and we have seen examples in some of the evidence, conditions that may not even exist.
Dr Spence: I suppose a good example would be something like depression. I know this might be touched upon later during the session. When I first started in general practice, there was a campaign called Defeat Depression.
Q91 Chairman: Was this an industry campaign?
Dr Spence: It was a campaign promoted through the Royal College of General Practitioners and the Royal College of Psychiatrists, but with industry backing it with money. That led to us being told that a third of people were depressed, that we should screen for it, that we should start using antidepressants early, and we did. If I think back five or ten years ago, we were diagnosing large numbers of people with depression, and we were prescribing many antidepressants. As time has gone on, I have certainly begun to realise that in some ways yes, there are many people who do have depression, but lots of people are just unhappy and that is a part of life. So there is a whole generation of people coming up who almost feel that being unhappy is an abnormal state, which, of course, it is not. That is part of the backlash against the use of antidepressants. The public as a whole are beginning to realise that.
Dr Iheanacho: I would like to echo a lot of what Dr Spence has said. Your question related to how things might be different if the industry were not active in the way that it is. The plain answer to that is that there would be a lot more focus on things that the industry does not do so well or is not so interested in, such as non-drug measures and so on. It would be a mistake, I think, for anyone to equate the activities and interests of the industry with necessarily promoting public health.
Dr Wilmshurst: There would also be a major impact on medical education. There is a requirement for people to undertake a certain number of hours of medical education, 50 hours a year, and most of that is funded by industry, directly or indirectly. Whenever I go to a lecture at the postgraduate institute in my hospital, the room hire is paid by a drug company, as are the meals that you get, and the NHS would have to find the funding for that because there is inadequate funding, and government is tied in with it. Next week there is a conference at the Royal College of Physicians, at which the key speaker is the Deputy Chief Medical Officer, and industry sponsors that meeting: it is £2,000 a time to have your logo on the bag; £6,000 a time to sponsor part of the cocktail reception for the delegates. Presumably, the NHS is happy that industry sponsors.
Chairman: We will come on to the education aspects a bit later on.
Q92 Mr Jones: My early questions are general. Which group of people would you say hold the reins of control over the medicines that we take and how, if at all, has that control changed over the last decade or two?
Mr Vidler: Obviously, as you have already heard in evidence from the Department of Health and MHRA and others, the Government believes that it is gaining a firmer control on what medicines are prescribed and to whom, but in our evidence we quite clearly set out, I think, a number of ways in which that is not the case, areas in which the pharmaceutical industry continues to have undue influence. We pointed out the multi-pronged marketing approaches that the industry uses whereby it will use disease awareness campaigns, for example, to raise public awareness of conditions, as Dr Spence said, such as mental illness, and what can be quite trivial conditions such as toenail infections. What those awareness campaigns will do is encourage the public to go and see their GP, often in quite strong terms, saying, "Go and see your GP. Be forceful. There is something that can be done." Simultaneously, the companies will be advertising specific drugs to those GPs, and what our research with GPs earlier this year showed was that GPs were aware that all this activity was going on, but quite often it was easiest for them to take the path of least resistance, and if they had patients coming in and saying, "I have this condition. I have been told you can help me treat it," they will say, "Yes," to save themselves time, even though they may feel it is not the most appropriate prescription in those circumstances.
Q93 Mr Jones: Has that influence changed over time?
Dr Iheanacho: First of all, in terms of who controls what is prescribed or what is used, which was your original question, clearly there are multiple influences on that, but one of the key strands that pulls it all together is the role of the industry, because the industry is involved in all of the key stages, whether it is the decision to make the drug or medicine, give it a licence, how it is marketed, whether it is the education and other information that goes to doctors, other health care professionals and patients, whether it is its role with government in terms of government championing industry's competitiveness or other activities, and so on. It is difficult to see, if you take any key stage which leads to the use of a drug, where industry does not have a rather powerful and I think an unchanging role really. There is nothing to suggest that that influence has weakened over time. If anything, I would say it has become stronger.
Dr Spence: Certainly in surgeries much of my experience about change in influence comes from the pharmaceutical industry and from the use of drug representatives, and their contact with the doctors can almost be on a daily basis. Certainly my contact with the industry via pharmaceutical reps five years ago was on a daily basis. That can lead to very wide variations in a local area in the prescriptions of drugs. Taking the situation of Vioxx recently, in our local area, within a very short space of time, within three or four years, that class of medication became 40 per cent of the particular group of medicines that we were using, and there was a very wide variation between different practices on how that was conducted. That is despite the recommendations.
Q94 Mr Jones: Can I ask a naïve question? GPs are very busy people. We hear constantly that they have no time for more than five minutes per patient. Why are they wasting all their time seeing pharmaceutical companies?
Dr Spence: It is not a naïve question. The reason is that you know these people. I feel slightly awkward about being here because I do not want to seem unkind to the people I have known as representatives for years and years, but I feel like I have to be. The reason we see them is because you have a personal contact with them. Often, certainly in the areas that I work in, they provide lunch on a daily basis to many of the doctors and nurses in the area.
Mr Jones: So when I want an early appointment with my GP, I am going about it the wrong way; I should offer to take him out for dinner.
Q95 Chairman: Has the advent of primary care trusts changed these practices in any way?
Dr Spence: No.
Q96 Chairman: That is interesting, because obviously there is a much greater degree of monitoring of prescribing practices of individual GPs within PCTs. What you are saying is that the practices we have all heard of over many years of the kind you have just described continue without any impact?
Dr Spence: Yes.
Q97 Mr Jones: Can I move on to a different though again a fairly general question: what is the connection between the development of new drugs and the improvement in therapy? How well-connected or not are these two processes?
Dr Wilmshurst: I do not know if they are really. It relates in part to the previous question, because I think the pharmaceutical industry also influences the research that is published. I know from experience. One reason I am here is that I was offered a bribe of two years' salary not to publish research which was counter to the interests of the company making the drug. I know other people were influenced because of that not to publish - not because of bribes but pressure was put on other researchers working on the same drug.
Q98 Mr Jones: I think other questions will begin to explore that particular area but can I ask you more generally. One might again take a naïve view that every time a new drug comes into the marketplace, there is a new cure being proposed. Can you broadly explain what the relationship between new drugs and new cures is.
Dr Iheanacho: There is an uncoupling in the relationship you have described. The advent of new drugs often has very little to do with new cures. If you look at all the drugs that are licensed in a particular year and critically assess whether these actually constitute genuine innovations for patients, you would be surprised, I think, to find that relatively few of them do, and a decreasing number do. That is the important thing. The ability of industry to produce genuine innovations is going down - there is no secret about that - partly because it is expensive and difficult to do. When you see a new drug, you always have to ask yourself the question which we do: what does this actually offer as an advantage compared to what I have already, or what my patient has access to already? They are not coupled at all.
Q99 Dr Naysmith: I was interested in what Dr Spence was saying in relation to depression and how people were being encouraged to think they are depressed and you can have a drug treatment for it. When I discussed this matter, as I have before, with general practitioners, they tell me that they know that some kinds of talking therapies would be a lot better for their patients than giving a pill, but you just do not have the time to do that. Is it compensating really for not having the time to talk and try and sort problems out, or is it just a way to get patients out of the practice more quickly?
Dr Spence: It goes back to agenda setting. It goes back to saying, "What is the priority when it comes to treatment?" From the point of view of talk therapies, that could come from the primary care trust. The resources that are spent or used for, say, antidepressants, which can be up to £80 a month worth of antidepressant medication, could be freed up to provide talk therapies, but it is because the industry are very effective at drilling their line of intervention. It is treatment first. The people involved in talk therapies do not have the same levels of influence and access to the people who make those decisions.
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, which they do, 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 that. 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 this data and make it 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 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 reporting in terms of 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, what a minor effect is; it is going to cause 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 for 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 have a safety concern 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 "Hold on a minute. We have had this drug for ten 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 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 any 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 ten 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.
Q120 Dr Naysmith: Who would have authorised the certificate and how could it be possible that you thought there should be a certificate and there was not one?
Dr Wilmshurst: Because the company sent us a letter saying they had got it.
Q121 Dr Naysmith: Who should they have applied to to get it?
Dr Wilmshurst: The Committee on the Safety of Medicines.
Q122 Dr Naysmith: Had they not been asked at all or had they refused to give one?
Dr Wilmshurst: They had not been asked. However, if I had suspected initially that they had not got one and asked them, they would not have told me anyway. It did not occur to me that they would not have one when they said they had, but if I had asked the Committee on the Safety of Medicines, they would not have told me anyway because it was confidential between them and the company.
Q123 Chairman: You have got to be of a certain age to remember a Conservative government. Some might say that your evidence here is a little bit out of date. How would you say the current practices are similar? Have you evidence that is more up to date than 20 yeas ago?
Dr Wilmshurst: I had a meeting with the Chief Medical Officer two years ago and gave him other examples of serious research misconduct. I have written to him repeatedly since then asking what he has done about it, and I get a postcard acknowledging my letter.
Mr Amess: This is much more interesting!
Q124 Dr Taylor: Can I go back to Dr Spence. We are led to believe that generic prescribing is being used more and more. We are led to believe that general practices have their own drug formularies more and more. Are these not lessening the effect that the drug companies can have?
Dr Spence: I reflect the question back to you: has that had an impact upon the drug costs to the NHS, which still stand at £9 billion per year, rising at an annual rate of 8-10 per cent? Evidently not. The greatest cost to the NHS are not the generics but the branded drugs. You are probably aware of the issues about accusations of manipulation in the generic industry a few years ago anyway, and I think a number of companies were fined over that. As for the use of formularies, these are not compulsory formularies and there is a huge variation from practice to practice. Within a certain area there may be even a twofold difference in what GPs prescribe, and there is no way of controlling that.
Q125 John Austin: You mentioned the prescribing habits of doctors. If I could pick out an example, there has been an enormous explosion in the cost of prescribed drugs for indigestion and the use of proton-pump inhibitors. There is some concern that they are being prescribed indiscriminately when there are more traditional and cheaper methods which might be effective. To what extent do you think that the alleged over-prescription of PPIs is as a result of pressure from the pharmaceutical industry?
Dr Spence: It is all about pressure. In fact, I wrote the complaint to the ABPI about the promotion of a PPI known as Zoton Fas Tab. What was happening there was the industry were using a third party to come into general practice to switch patients from Zoton to Zoton Fas Tab because Zoton was coming off patent. The PPI market is huge and the representatives were very effective at persuading practices to allow the switch to happen.
Q126 Dr Taylor: Going back to drug formularies, would it be feasible to have PCTs producing standard drug formularies for their particular area and in some ways getting them enforced? Hospital formularies seem to be much more widely used and accepted.
Dr Spence: It is certainly my experience that that is not the case. In our area we have something called the Glasgow Formulary, which is produced jointly between the hospitals and the PCT, and there are great variations between which hospitals use which medications and which medicines consultants use. The problem is that the authorities are very reluctant to take on the medical professions because the medical professions tend to hide behind this idea that we are professionals and we know best, so it is very difficult to enforce a formulary upon hospitals and doctors and general practitioners.
Q127 Dr Taylor: Should that be one of our recommendations?
Dr Spence: Absolutely. If you assume that the drug costs in the UK over the next year or two will go up by £1 billion, which is a likely projection, you have an enormous financial responsibility to contain this. I do not want to quote the Leader of the Opposition, but apparently £1 billion would put an extra 40,000 police officers on the street. That might be something worth considering. You might be better off putting 40,000 regulators into the drugs industry and find out what doctors are actually doing.
Q128 Dr Taylor: Is it fair to ask you whether there is any move among doctors to be less receptive to the freebies?
Dr Spence: Yes, I think there is. I can quote a survey, an online survey in the BMJ of 1,500 respondents. I think they were largely doctors. Ninety-six per cent of them said there should be transparency in the relationship between the industry and doctors, and what we are calling for is a compulsory register, in the same way as Members of Parliament have, of contacts and hospitality received from the industry. If there is not a problem with the industry, let your peers and let the patients decide. It will be important for the NHS to take that lead, because no other country has done that, and the onus of responsibility should rest with the industry because they know who they are seeing and they know how many contacts there are.
Q129 Dr Taylor: So another of our recommendations should be that doctors should report in detail their contacts?
Dr Spence: Yes, but the problem with self-reporting goes back to the problems with the yellow cards. Rest it with the industry. They have the infrastructure and they know who they are seeing at the moment. If the industry has nothing to hide, let them publish this information.
Dr Taylor: Certainly when we get them before us we will want to ask them about their expenditure on advertising and drug reps.
Q130 Mr Jones: I just want to intrude in this discussion between the two doctors and say there might be another way of looking at the problem. The problem that you are describing is a problem of undue influence of the industry over GPs in their prescription practice.
Dr Spence: Not just GPs but hospital doctors as well.
Q131 Mr Jones: Largely GPs in terms of the prescription of pharmaceuticals, I think. Instead of looking at it from one end of the spyglass, looking at how we regulate the industry in order to reduce the undue influence, you might look at it the other way round and say that perhaps we should look at the gate keepers. If we remove a great deal of the control the gate keepers, ie the GPs, have over which drugs they prescribe, that might be a more effective way of dealing with the problem.
Dr Spence: Yes. There is a problem. You have to seek to resolve it. Our perspective is that we want to use resources like the Drug and Therapeutics Bulletin to deliver effective and cost-effective treatments to patients. How do you deliver that? There are lots of different models, but you need to tackle this problem.
Q132 Chairman: That thought was behind my question some time ago, when I asked you about any changes to these practices through PCTs, where there has been a more collective discussion about prescribing practice at a local level. You said that might be happening, but the practice of inducement through the lunches side is still there.
Dr Spence: I suppose if the PCT were more proscriptive to the doctors who work for them - notionally they are independent contractors but in fact they actually work for the PCT - the industry's influence would be much less, but they would exert that influence at the PCT level rather than the medical level. There are lots of different threads to this, but certainly a more prescriptive formulary would be one end, but I do believe very strongly that there has to be some register.
Mr Vidler: Can I just add that it is important that we do not lose sight of the fact that the industry also has a direct influence on consumers, and in those circumstances it is not feasible to imagine that we can quickly build up consumers' knowledge and understanding to a level where they can cope with it, and in those circumstances we do very much need to focus on regulation of the industry.
Q133 Mrs Calton: Dr Spence, could you say whether you think that doctors who actually resist contact with the pharmaceutical industry and reps actually prescribe more appropriately?
Dr Spence: That is a difficult thing. I suppose the reverse is true; there is some evidence that if you see more pharmaceutical represents, you prescribe more of the new drugs, so conversely I guess that is true. Again, it is slightly anecdotal, but in my experience, those people who distance themselves from the industry do practise in a more effective and cost-effective way.
Q134 Mrs Calton: If promotional activity is severely curbed, it seems highly unlikely for economic reasons that any major pharmaceutical company could operate with acceptable levels of profit. Do you believe that that is so?
Dr Spence: What does "acceptable levels of profit" actually mean, seeing as the pharmaceutical industry has been the most profitable industry throughout the 1990s, and despite the downturn in the market has still maintained enormous profits throughout? Reasonable profits? They are unbelievably profitable already.
Dr Wilmshurst: I just wanted to mention the point that there is a lot of discussion about the interaction between pharmaceutical reps and GPs, but in fact, the companies influence GPs I think rather more because GPs are sceptical about what reps tell them. They are influenced more by opinion leaders, which is why the pharmaceutical industry pays opinion leaders so much. The senior people can get £5,000 plus for one hour's talk to their colleagues in cardiology, and that is obviously because that is how much the pharmaceutical industry rates those people.
Dr Spence: That happens at a local level, with local specialists coming in and giving messages to local GPs, and these guys are being paid very handsomely for delivering their message - an independent message but...
Q135 Mrs Calton: I accept absolutely and from the evidence that you have been giving that an enormous amount is going on. The question is, what would happen if you withdrew all of that, or if you regulated it so heavily that it did not happen?
Dr Spence: My view is you would have a much more appropriate and better health care system.
Q136 Mrs Calton: Can we move on to consumers, the public. What is your view on the part the pharmaceutical industry has to play in informing the public about the medicines they make and how they might be used? We touched on this earlier.
Mr Vidler: We believe it potentially has an important role to play, and clearly, the industry has widespread experience of marketing and great skills to bring to bear in translating that into education. The problem with what is happening at the moment through disease awareness campaigns is that people are not being given a holistic view of the situation. They are being given a view which leads down a fairly narrow track to a drug-based solution, where that may not be appropriate. That sort of information and that sort of awareness-raising has its place but it needs to be part and parcel of a holistic approach.
Dr Iheanacho: I obviously echo a lot of that.
Q137 Mrs Calton: In a sense what you are saying is that it is more of the nature of propaganda than it is of true information in the round?
Mr Vidler: We would need to distinguish. There is obviously a spectrum of disease awareness campaigns and promotional activity. At one extreme of that spectrum, you are fairly close to propaganda. There are some less bad examples as well.
Q138 Mrs Calton: Could you give us a broad view of the effectiveness of self-regulation in drug promotion? I think from what you have said already you feel it is not particularly effective.
Dr Iheanacho: No. I suppose it is being generous to say it is not effective. I would say that the self-regulatory bits that we come across in terms of promotion of particular medicines to doctors, for example, are very weak indeed. In some sense, their activities are so questionable in terms of actual regulation that you have to ask why they are there at all. The conclusion that I think I have reached is that they are there because they need to be there, so that if somebody asks "What is the regulation?" people can quote to them and say "There is the regulatory system." But if you were looking for evidence that this is a system which acts in a way that I think most reasonable people would want a regulatory system to act in terms of advertising, that is, it can spot misleading advertising quickly or react when misleading advertising is brought to its attention, can investigate it quickly and stop it happening if necessary, punish whichever company is doing it effectively and be seen to have done that; crucially, inform the people who have been misled quickly and as widely as possible that they have been misled, and act as a deterrent to that company or someone lese doing it again. If those were the standards that you wanted to see operate in a regulatory system, they are in my view largely absent from the present regulatory arrangement.
Mr Vidler: We have suggested for that reason that the current web of regulation and self-regulation over advertising and promotion needs to be replaced by one single independent advertising unit.
Q139 Chairman: Can I conclude by picking up a couple of points that have come out in the session so far. Dr Wilmshurst, you mentioned a few moments ago the way drug companies will pay eminent cardiologists £5,000 for an hour's session to talk about their products. How widespread is this practice, and do people not see through what is going on? Surely, people can make up their own mind as to the merits of this practice.
Dr Wilmshurst: People do not always know, because people do not always declare their conflicts of interest.
Q140 Chairman: So this comes back to the need to make public where money is being received, the issue that was raised a moment or two ago.
Dr Wilmshurst: Yes, and even if people declare their conflicts of interest, they do not often tell you how big the conflict is; they do not tell you how much they are getting. It is well known that in fact there are lots of cases where conflicts are not declared. In the majority of cases they are not declared, and where they are, there is no mention of the actual sums involved. Some people - this is in some of the written evidence I have sent - were earning considerably more from individual pharmaceutical companies by talking for them every fortnight, twice a month, than they were earning from the university or the NHS that they work for.
Q141 Chairman: So this is quite a common practice, you would say?
Dr Wilmshurst: It is very common. It is the only way that many academics can achieve the salaries that their NHS colleagues do in private practice, because in cardiology, if you do private practice, you can earn very considerable sums, hundreds of thousands of pounds a year. If you did away with it, you would have no academic cardiologists. It is almost impossible to appoint academic cardiac surgeons in this country because a morning's work would earn you £5,000 for an operation.
Q142 Chairman: One of the things I was interested in from the evidence we have got from yourselves was the extent to which continuing professional education of doctors in particular is very much financially supported by the industry. What proportion of continuing professional education would you say is typically funded by the industry?
Dr Wilmshurst: Ninety per cent plus.
Q143 Chairman: As much as that? Can you give us a quick summary of what would be the appropriate level of influence of the industry? Certainly you are arguing that the industry is very influential, and influential in ways that are very much open to question. What would be, in your view, an appropriate level sufficient to sell the products but not to the extent that we have now?
Dr Spence: I think there has to be transparency between all the agencies and the industry.
Q144 Chairman: So more transparency would be your response on the issues of the kind we have just been talking about?
Dr Spence: Yes.
Q145 Mr Burns: Very briefly, Dr Wilmshurst, from your written evidence and what you have now said in answer to the Chairman, this is a matter of grave concern. You said in your oral evidence that it was common practice and it was well known. Do you think briefly, for the public record, you could give us some specific examples?
Dr Wilmshurst: Yes. I attended a meeting, a satellite symposium, at the British Cardiac Society a few years ago where a number of eminent speakers spoke about a drug called Posicor - that was the trade name. I knew a couple of them and I spoke to them afterwards, and they really had no experience of use of the drug but were prepared.... I did not ask them how much they earned.
Q146 Mr Burns: Did you ask them though that they were earning something?
Dr Wilmshurst: I am sure they were.
Q147 Mr Burns: But did you ask them?
Dr Wilmshurst: No, I did not. OK. I will have to check my records. There is another company - I just have to remember which company.
Chairman: It might be helpful if you came back to us in writing.
Mr Burns: I would quite like an answer to my question first.
Chairman: He is not able to on specific examples.
Mr Burns: He has made the allegations, so surely he can back them up.
Chairman: Of course, but what I am asking is for him to follow up in writing with detail that he probably cannot give at the moment.
Mr Burns: If it is a very common practice and well known and he has submitted written evidence, surely, given the seriousness of it, Dr Wilmshurst should be able to give us at least one oral example for the record.
Chairman: He has just given you one.
Q148 Mr Burns: He has not actually. He tailed off.
Dr Wilmshurst: If I might finish, I will just tell you about the Posicor, if I might. The doctors that I spoke to I assumed were earning money because I knew ----
Q149 Mr Burns: That is an assumption, not necessarily a fact.
Dr Wilmshurst: ---- because I knew that one of the two I spoke to was in fact also employed by another pharmaceutical company, Rhone-Poulenc Rorer, and he was a member of what I have described in the literature as the "roadshow" and would earn between £2,000 and £5,000 a time for speaking plus travelling expenses in this country. He spoke about once a fortnight with one of his colleagues for the company. I have this from a representative of the company. The company called the pair of them "the roadshow" and they travelled around, talking about a drug made by the company. Also afterwards I spoke to a colleague who had done similar work for a company making Captopril, and in fact his experience was quite bad. He had gone off message, and unfortunately he was in Amsterdam at the time, and they refused to bring him back, so he then had to find his own way back. That is what happens if you go off message. So there is an incentive. If you are getting a large amount of money from the company, there is an incentive to keep on saying it because one, the money will dry up if you say the wrong things, and of course, there is also the danger you will embellish it because you are trying to make it sound even better.
Chairman: Can I ask on behalf of the Committee that you follow up in writing to satisfy the concerns that Simon Burns has, and give as much evidence as you can of the examples you are referring to, because obviously this is a key issue from our point of view.
Mr Burns: So as not to delay things any longer, can I just add to what the Chairman has just said that when you do come back, we are looking for specific examples of eminent cardiologists getting up to £4,000 plus expenses for an hour-long talk on their products. Specific examples. That is the allegation you make, and I am not questioning whether it is true or not; I just want the evidence, because it is a very serious matter if the evidence exists.
Q150 John Austin: Earlier on you were talking about the importance of listening to the patients on issues of adverse reactions etc, and I think all of us would agree that the voice of the patients and patient organisations has to be listened to. It has also been suggested that in some cases there is a very cosy relationship between the pharmaceutical industry and some patient organisations, whereby patient organisations may be used by pharmaceutical companies to pursue their own ends. Do you have any evidence of that?
Dr Iheanacho: I have a clear example. The example I would suggest is GlaxoSmithKline's involvement with a small charity called Allergy UK. That involved producing a book, a little "Mr Men" book based on the children's character - here it is - and it is a very ordinary Mr Men book until you get to the back, where you find some advertising for some of the company's products. This book was in fact illegal and is no longer available; it had to be withdrawn. The law makes it very clear that children cannot be used as a promotional vehicle in this kind of way. In terms of the charity, the charity did not know about the problem, that this was bad behaviour, until they were alerted by the media, who pointed it out: "What is going on here? This isn't the done thing." So the charity was in a very embarrassing position because they had been acting in good faith but essentially they had been taken in by the company.
Dr Wilmshurst: I should have thought of this. I should have mentioned my own position, of course, because I have not declared any conflicts of interest, and perhaps I should. I am often offered money by pharmaceutical companies to talk. I do not ever take it. I ask them to give it to a charity, because I feel it would be invidious for me to take money for that, and I often receive several hundred pounds just for talking to local GPs.
Q151 Mr Burns: On what?
Dr Wilmshurst: About drugs, and about their drugs, but I only talk about drugs that influence me. I am also a consultant - this is slightly different - for a device manufacturer. It is covered by the Medicine Device Agency, so it is slightly different but it is a medical device. I have been asked to be a consultant for them, and it is difficult for me to do so because I am a specialist adviser to NICE, so I have agreed with them that they pay the money to a charity so that I cannot receive it. It is an overseas charity in Africa for kids with AIDS. I thought that would be a way that no-one could ever say I had a conflict of interest. But the sums involved for my few hours of work with them will be £22,000. That is the sort of level that they pay a DGH cardiologist. If you are a professor of cardiology somewhere else, you can earn considerably more.
Chairman: Can I thank our
witnesses for an excellent session. I
am sorry we have had to somewhat curtail it but it has been very helpful and we
are most grateful to you.
Memoranda submitted by Professor David Healy, Mind
and Professor Andrew Herxheimer
Examination of Witnesses
Witnesses: Mr Richard Brook, Chief Executive, Mind, Professor David Healy, North Wales Department of Psychological Medicine, University of Wales, and Professor Andrew Herxheimer, Emeritus Fellow, UK Cochrane Centre, Oxford, examined.
Q152 Chairman: Colleagues, we have one witness who will be with us in a moment or two. Can I welcome our second group of witnesses? We are grateful for your cooperation with the inquiry. Can I begin with an apology that I have to leave at 12.30? My colleague, Mr Austin, also has to leave at 12.30. Doug Naysmith will take the Chair. We mean no discourtesy; unfortunately we both have other commitments, but I hope we can get through the business by then. Can I ask you to introduce yourselves briefly, starting with you, Mr Brook?
Mr Brook: Yes. My name is Richard Brook. I am Chief Executive of Mind, the mental health charity.
Professor Healy: I am David Healy. I work in what used to be University of Wales College of Medicine, which has just recently changed into Cardiff University.
Q153 Mr Amess: As you know, gentlemen, this inquiry is called "The Influence of the Pharmaceutical Industry", but what the Committee would like to hear from you about is are there differences between the way the major pharmaceutical industries display their influence and actually operate? Perhaps if you could name a few of the companies and enlarge on the way you perceive their influence to happen in practice?
Mr Brook: I am happy start. My experience is limited to what has obviously been a very high profile issue around anti‑depressants, and I have seen, I think, quite clearly through my time sitting on the Expert Working Group which is part of much of the SSRI's investigation of the last two years into this, very clear influences, I think. You only have to look at, for instance, the Committee on Safety of Medicine's declaration of interest which has been recently uplifted to see three‑quarters of the committee actually have defined a personal or non‑personal interest, not defined in size, and you only have to realise that that raises a whole issue of transparency, and, as you have already heard in evidence today, the relationship between those members and the drug companies and what is going on. I do not want to make any allegations, but you just do not know - the transparency is not there. You ask for two very specific examples. The two that I would give at this point would be GlaxoSmithKline in terms of the issues of Seroxat and Wyeff, which I do not think has been generally mentioned before in relation to venlafaxine and effexor. Both of those companies had at least two years before the information went to the MRHA, evidence in relation to paediatric trials, and neither of them bothered to place that evidence into the MRHA's domain, and in both cases those drugs were subsequently contra‑indicated. I do not know about the other two drugs because the dates on the trial data was never given to me as part of that expert group, but the two that have got dates related to them, both of them had information two years prior to the MHRA having that information. I have raised that issue several times, it has been very high profile, and to be honest, to this date, as far as I know, nothing has been done about that; and particularly in relation to Wyeff, which, I think, is of particular concern, it has never actually been acknowledged, despite correspondence between myself and the MRHA, that that is an issue: because they claim it is investigated, they claim it is secret under the 1968 Medicines Act and they threaten prosecution if someone like me says that they will actually raise those issues in public.
Mr Amess: Mr Brook has chosen to be negative about two companies, but, the other two gentlemen, do you want to say some nice things about any‑‑
Chairman: I am not sure Professor Herxheimer heard your question. He came in part way through your question, so perhaps you could briefly repeat your question, and perhaps I could ask him to introduce himself as well.
Q154 Mr Amess: Would you tell the Committee who you are?
Professor Herxheimer: I am Andrew Herxheimer. I am a medical pharmacologist.
Q155 Mr Amess: As you know, this is an inquiry into the influence of the pharmaceutical industry, but there would appear to be differences in the way the major pharmaceutical companies go about influencing general matters. Mr Brook has just decided to be a bit negative about two companies. Would you gentlemen want to praise any of these major pharmaceutical companies or have you got some axes that you would wish to wield publicly?
Professor Herxheimer: I have had interactions with many pharmaceutical companies and I cannot recall one that I would wish to praise.
Q156 Mr Amess: Right. Well, that is that! What about you, Professor Healy?
Professor Healy: Okay, if I can come in on this. I think there is... One of the things I do is I go round and try and work on the history of the field, which means that I interview people who were working in the area during the Sixties, the Seventies, the Eighties, people who worked within the industry, people who were clinically whatever, and there was a feeling, I think, up to about ten to fifteen years ago that the practices of pharmaceutical companies based over in the US were somewhat sharper than perhaps the practices of the pharmaceutical companies based over here. I think that has changed now, and I think, broadly speaking, all of the companies take much the same approach. I would not, like Andrew Herxheimer, say that this is always a bad thing that he would not wish to praise. If you hold shares with pharmaceutical companies you want your drugs marketed most effectively, and I think almost all the companies take the same approach to these issues these days which involve an increasing proportion of the articles on which physicians like me actually depend being ghost-written, which involve those articles not actually reflecting the raw data from clinical trials that people like you, or your wives, families, get involved in, take risks with or are injured by these pills. The hazards that come out in these clinical trials do not get translated through to the articles that shape "formres". The issue was actually raised earlier: would we not be able to really sort this all out if we just had a decent "formre"? No; you would not, because the problem is not the ad', the problem is not the free, kind of like... Because what you find these days is people like me are brought to the Caribbean. We come out of the meeting halls with our arms stuffed full of bags of free gifts, free rulers, free pens, free mugs, that have the name of the drug on them. We have had our massage done, portrait painted‑‑
Q157 Mr Amess: You have had your massage done?
Professor Healy: People have a massage done, their portrait painted, and are ambushed by the media who hold up the mike and say, "Doctor, are you not influenced by this?", and the answer from people like me and almost all the physicians you would meet is, "No, we are not." The media say, "What does influence you then?", and the answer is we are influenced by the articles we read, the articles in the BMJ, the articles in the Lancet. If you look at the BMJ these days you will see an advert on the left‑hand page and an article, or the first page of an article, which appears to be a randomised controlled trial on the opposite page, and we all look at these things and think, "If only the BMJ did not have the adds in it, things would be fine, and if they had more of these articles which are controlled clinical trials, this is the way we need to move forward." But industry twenty odd years ago or so actually began to realise that, "Yes, if physicians say they are influenced by the evidence, what we are going to use to influence them is the evidence", and they began to go strike up the trials, and increasingly the articles that are written in the BMJ and the Lancet will not just be ghost-written but will not represent the raw data from the clinical trials that they purport to represent; and this can lead to the kind of situation where, if you make "formres", the drugs that you will put on the "formres" that appear to be the most evidence‑based will actually be less effective than the ones that you are actually removing from the "formres".
Q158 Mr Amess: Before moving to my next question, you have got an awful lot off your chest; you want to have a get together with the free lunch chap! Did you enjoy your time in the Caribbean?
Professor Healy: Well, yes, I am in a position to speak to all these things, and the issue was raised earlier, having worked very closely with the industry, having been a person who has actually spoken for the industry; so I know just what the practices are. The issue, the interesting issue for me has been just the issue of what is going on here. You hear very clearly from the industry that actually the sales department who want to give the free pens, the free mugs, they know that these do not have quite the influence that you think, and they even play on the fact that physicians like me know that we are not really going to be influenced by this, or at least we think we are actually not going to be influenced by this, but that we are going to be influenced by the articles. So the drug reps when they come round to see me will have the free pen and the free mug and the sheaf of articles, and this is the advert these days.
Mr Amess: This is all very interesting. Members of Parliament could never be influenced in such a way!
Q159 Mr Naysmith: The pharmaceutical industry is not going to be terribly pleased with what you are saying today. I just want to know what produced the road to Damascus moment for you?
Professor Healy: Nothing in particular. I have actually been writing about these issues for the last fifteen years or so. There has been no particular change in the issues that I have actually been writing about.
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 think 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 think 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, nine years ago I was involved in the same issue around drugs like Vallium and 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 a post‑licensee came up to me and said, "Were 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 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 interests. 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, but 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, is the previous ‑ had a 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 we 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 the JD. I cannot understand why enforcement needs to actually have that experience. I can understand why your enforcement agency might have 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 Wyeff.
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 DOH does not have that. Just a little cameo: after the effexor regulation the Department of Health official turns up at the meeting, the next 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?
Professor Healy: 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 and the US - and we have seen the unpaid cheque - 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 peaked 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, etcetera. 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, etcetera, and that meant that many, many things could be discussed in the regulator, in the regulator 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, etcetera - 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 licenses are refused on a drug the company may appeal, and it is then heard by a formal appeal of the Medicines Commission ‑ that is one of the jobs. No‑one else may appeal. The evidence may be as ropy 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 to 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, etcetera. There are two dimensions that also need to be considered in your thinking: one is funding, because clearly if you look at the ABI's submission, the PPI'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, we have ‑ 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 raconteur, 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 the playing not only with the pharmaceutical companies but actually playing in terms of how the European regulatory world sees you. So I think you have two issues: one is economics and one is 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 lay position sort of conflict issue, 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 this 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, etcetera, etcetera, 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.
Q180 Mr Burns: Professor Healy, I do not know if you were present for the earlier session?
Professor Healy: Yes, I was.
Q181 Mr Burns: So you will know what I am talking about. There was an exchange of questions with Dr Wilmshurst where he in his written evidence has suggested that drug companies would pay eminent cardiologists and others up to £4,000, plus expenses, for an hour long talk on their products. Maybe you will be able to help us, because I see from your CV that your background is in consultancy work with pharmaceutical companies and in recent years you have acted as a consultant, conducted clinical trials, spoken or attended foreign meetings, and then I see about three and a half lines of pharmaceutical companies that presumably you have spoken for or acted as a consultant. Is it your experience that you could earn up to £4,000, plus expenses, for an hour long talk?
Professor Healy: I think, as you might actually expect, general psychiatrists probably come somewhat cheaper than cardiologists, but, yes, if you are asking me in the course of a day, in the course of work for a day or so, could people like me be paid of the order of £4‑5,000 per day, the answer is, "Yes". Do I think that there are people in the field who are at a higher echelon than me who perhaps have closer links to the regulatory apparatus than I have who would be being paid more, the answer is, "Yes". The industry is also very clever in how they organise these things. For instance, if I get perhaps contacted... If I am working in a consultant capacity for one of the pharmaceutical companies, I will have had media training often, and the understanding is if the media were to get hold of you... Let's say some issue blows up about some pill and the media get told, "You can approach Dr Healy", for instance, I will be able to say, and the media and also the pharmaceutical company will be able to say, "Well, no money passed hands." When I was asked by the Guardian, for instance, "Is there a hazard with these pills?", there will not have been any money that has actually passed hands from me doing that piece of work for the pharmaceutical company, but the money comes from elsewhere; it actually comes from the trips to the Caribbean; it comes from being asked to chair meetings which involve no work at all; it comes from having my papers written for me and then I am paid as though I have written the papers. That is where the money comes from.
Q182 Mr Burns: Do you have that done for you?
Professor Healy: I have had papers written for me, sent to me, and I have said, "No, I actually planned to get involved in this meeting, I had actually planned to write my own paper." The pharmaceutical company in question was rather surprised at this. When they saw the product that came back to them, they said, "This article that you have actually written is quite good. We think we will hold onto it, but there were certainly important commercial points in the one that was done first, so we are going to have that as well", and they altered just one name, the name of the author, Siegfried Casper, Professor of Psychiatry in the University of Vienna, who could be not a more symbolic name in all of psychiatry than professors of psychiatry from the University of Vienna. His name ended up on the piece. How much he was paid for it, you will have to ask him.
Q183 Mr Burns: Per se do you think it is always wrong for money to change hands or is there a valid area where it is justified?
Professor Healy: No, I do not. A great proportion of what I have had has gone into research funds. There is a charity that I have also fixed up out of which I am unable to get any funds at all; but the issue is not the funds changing hands, and the issue is not the articles being ghost-written per se. I could live in a world where the editors of journals had links to all of the major companies, where people speaking on company platforms had links to the companies; I could live with their articles being ghost-written. The crucial issue is not all of those. You do not want to tinker with things at the edge: the free pens, the ghost-written articles; the key issue is whether these articles correspond to the raw data that comes from clinical trials that your children may have been involved in for instance: that is the key point that you need to get at.
In the absence of the Chairman, Dr Naysmith was called to the Chair
Q184 Dr Naysmith: The more perceptive of you will have noticed that the Chair has changed. David has now left us and a different figure is in the Chair. David, I think, apologised earlier that for family reasons he had to go. I think we have a number of other areas we need to ask a few questions on yet, if the panel are happy to go on. I was going to ask again Professor Healy, who seems to be rather dominating this panel a little bit ‑ we will have to let the other two have a say in a minute or two ‑ you were talking just then in answer to a previous question about secrecy in drug trials and that there are things that are known that are not published and made public knowledge. When I had a proper job I used to be a scientist and one of the difficulties always was publishing negative results and what you do with things, goodwill designed experiments that come up with the answer that something does not happen which I supposed to happen; and I imagine the same sort of thing happens with drug firms, to a certain extent, that you get your correct information and it does not really tell you much one way or the other. Before I finish the question, there are two aspects to this, efficacy in whether the drug is any better than something that is on the market, and obviously the firms will try to argue that it is, and then there is the question of danger and possible risk and hazard. What is your answer to what we can do about all this: getting negative results that are meaningful?
Professor Healy: Very quickly, and this is where I ought to hand over to people like Andrew, who has much more experience in this sort of field, but awfully quickly, the SSRIs, for instance, take one of them centrally, of the first sixteen trials done ten showed that the drug did not seem to work at all, two‑thirds of the trials do not show this drug works. The adverts for the drugs say, however, that this is a drug that has an unparalleled evidence of efficacy. In essence the position that New York State took recently viz GlaxoSmithKline not publishing clinical trials where the drug had not been shown to work was that this was fraud. How can a physician give a drug to a person like you or your wife or your children when they do not really know what the true picture us. I think there is a real issue about the clinical trials that do not show that the drug works not being published, but there is a bigger issue about the ones these days that are being published. The biggest hazard, the thing that influences me and all the rest of us the most is the trials that are in the BMJ and are in the Lancet but actually are a distorted picture of what the raw data looks like. These things really do influence us even more than the trials that were left unpublished.
Mr Brook: If I could just say, I do have an issue here, which is that, for instance, on the expert group over the 10 years Glaxo were asked to provide trial data on Seroxat and they produced over 180 trials and pieces of work, much of which has never been put into the public domain. Interestingly, the issue around children and paediatric work, what happened there was they actually wrote to the MHRA asking for an extension of their license and they actually referred to the depression trials that were subsequently looked at by the expert group; and what they actually say is, "These trials have not quite worked out, but rather than seeing them as negative trials", i.e. giving a negative result, "we believe they are failed trials" ‑ in other words they are flawed ‑ and actually there is correspondence between Glaxo and the MHRA bringing that out as a very, very clear picture; and I think that happens quite a lot, that people are actually saying, if a trial does not quite work, as there seems to be common acceptance in the work that I was involved in, that actually you just call them failed trials rather than negative trials, and it is, of course, very hard because the trial data is not in the public domain, people do not look at it and those assessments are very hard to be challenged; and so I think we have a real issue about trial data, and I think there is a real issue about our regulator and how robust it is in actually seeking that.
Q185 Dr Naysmith: At what stage should such data made available?
Mr Brook: I think we are beginning to see some changes, which are very welcome but again need to be driven by regulation and law, by my view: one is obviously the beginning of having to say that all trials need to be registered before they start so you can actually track what is happening to trials, how many are getting out into the public domain; secondly, again drawing a much better line on this so there is guidance about how good trials can be constructed; and I think trials should be signed off as being constructed appropriately, because time after time in the work I was involved in people would say, "We cannot use this trial because it has actually been done the wrong way basically", but I know Andrew has more to say.
Q186 Dr Naysmith: He is really saying, Professor Herxheimer, that you are the expert?
Professor Herxheimer: I think that there are two aspects to it. Negative trials ‑ I agree with what Richard Brook has said ‑ you would have to have registration of trials at inception, and ethics committees have to demand that a trial be registered before people are recruited to it, otherwise it should not be legal; and I think that requires a change in regulations or law. The other aspects of negative are the adverse effects. These are unwelcome to everybody and they are euphemised or disregarded or just not noticed; so that the resources spent on detecting adverse effects or suspected adverse effects, adverse experiences, by the people who take part in trials, how you actually collect those and investigate them makes a huge difference to what the data set is about that drug. To give one very simple example, if you do nothing to investigate them and only record those that are mentioned spontaneously by people taking part in a trial, you get a very small number saying, "I had this and this happened." If you ask them a general question, "Was there any change that you noticed while you were on the drug of any sort", then you get more, you get some, but if you ask for specific effects then you get much more specific answers: people know what you are talking about, what you are expecting. These methods are not described in the clinical trials reports very often and the amount of space given to adverse effects in clinical trial publications is on average as much space as is given to the title and the authors and their affiliations.
Q187 Dr Naysmith: This sort of criticism has been going on quite a long time about the design of clinical trial. Is there any evidence that they are getting better?
Professor Herxheimer: The International Committee of Medical Journal Editors has made recommendations about that and the journals that take part are applying better standards, and there is an international statement, consensus statement, on the reporting of randomised clinical trials which also has raised the standards enormously. The second version of that, which deals with adverse effects, is coming out in a month or two; previously it did not deal very well with adverse effects.
Q188 Mrs Calton: I was going to ask whether you had a specific example, Professor Herxheimer, of where a pharmaceutical company did not adequately investigate side-effects?
Professor Herxheimer: Well, because their investigations are secret, I have no idea.
Mr Brook: Could I just say that there is actually a role for the regulator here as well, because the regulator in March of this year, when I asked them, had never bothered, for instance, to look at the adverse report data from the FDA, and there is no arrangement, for instance, for adverse reporting data in other regulatory areas to actually exchange data, so we are only looking at the UK data anyway when actually all of these drugs are used world wide. So there is a real issue about that as well.
Professor Healy: Can I add in on that point. It is clear that in the trials of the SSRI's, people who have gone on to become suicidal have been coded under the heading of "nausea", they have been coded under the heading of "treatment non‑responsiveness", but in the group of trials Richard has seen, the group of trials in children, children becoming suicidal have been coded as being "emotionally labile", and this is a thing that very few physicians or people in the street ‑ actually it was a person in the street from the media that picked this up; it was not actually any of the physicians that read the articles that appeared or heard the talks given that actually picked this issue up ‑ children becoming aggressive and even homicidal were coded as "hostile". This is the kind of thing that slips under the regulator radar awfully well and under the physician's radar also, and this happens widely.
Q189 Dr Taylor: Can I go on, Professor Herxheimer, with the adverse effects of drugs, because in your paper you gave us you give some recommendations about what should be done. Would you like to spell those out and expand on them? We have already got the message that certainly the consumer is somebody who should be reporting these sort of things. Can you expand on your recommendations?
Professor Herxheimer: Yes. Because the regulators are funded by industry, they have no funds for doing any work of their own, and the work on adverse effects of medicines is absolutely to do with the public health, it is not to do with industry; and that is a public responsibility and it should be possible that the official organisations, including the MHRA, Medical Research Council and so on, should be able to investigate adverse effects independently - academic institutions. I think there is an argument for separating the whole analysis and collection of data on adverse effects from the MHRA, but clearly there are various ways in which that could be done. One way would be to have separate organisations doing it in the way that scientific research is done. There is a scientific community and there is an adverse effects community and a pharmacovigilance community, but that is all governmental, and I think that is very healthy because it has this close relationship with the industry. So, independent collection of analysis and investigation could be funded by a modest levy on sales of pharmaceuticals. This problem is also reflected in the very small staff. There are far more people employed on evaluating applications for licenses than there are who are evaluating the whole pharmaceutical market and what happens to the drugs afterwards and the people who take them. There is an enormous disproportion, and these are very hard working people, but it is impossible for them to do a proper job.
Q190 Dr Taylor: You have certainly given us some suggestions of where we should be looking to make recommendations. I am sorry to go back to the yellow card system, but it has suddenly occurred to me that in the West Midlands we had to send yellow cards to the university department. Is that widespread? Did that mean that more reports were sent in from professionals?
Professor Herxheimer: No, I think the reason for that is that you want these reports to be discussed locally and people to learn from them locally and to have an involvement ‑ people should feel involved ‑ not send them off to a black hole in London, and I think that has happened to some extent, there has been more discussion and there have been better reports, but it is still quite inadequate; so it has been a bit disappointing.
Professor Healy: If I could just quickly add, this is a point about the reporting of adverse events that should not be seen as industry hostile. Industry to date, as you have heard earlier, has not actually been bringing new drugs on stream all that well. The research, the hypothesis driven research, to get new drugs is not working. Our biggest single source of new drugs still remains adverse events. Viagra was noted because of an adverse event; so it is the kind of thing that should be feasible to have sold to industry as a thing that both they and the consumers and the rest of us can gain from. There is a value in trying to see what these drugs do.
Q191 Dr Taylor: The other effects--
Professor Healy: It is not just trying to penalise the pharmaceutical companies.
Mr Brook: Can I also just say that a large number of patients do not manage to succeed in getting their adverse effects reported. That is a consistently big issue for Mind. We have evidence over several years of people trying to report going to their GP, asking for adverse effects to be reported and the GP saying, "I do not think that is actually what has happened and so I am not doing it." I know patient reporting is now starting, but it still, I think, raises a real issue, and again you have got a number of case studies of that. The other issue that really worries me is the fact that the adverse reporting is seen as very minor in relation to clinical trials, and time after time I have been told that adverse reporting only can give a signal and it is clinical trials that are definitive. I think that is wrong. Those two must be married up. If we have got a large amount of adverse reporting we must understand what is happening here. I think it is really interesting, Seroxat had the most adverse reporting of any drug world wide and yet it has taken all this time to sort it out. The last point I would make, which I think is a very relevant point, is it takes 40 days for the MHRA on average, in the last annual report, to licence a drug and yet takes it two years to review anti‑depressants; and so there is something about the balance that Andrew was talking about that raises a real issue. If it takes eight weeks to get a drug into the market, why does it take two years sort out its safety afterwards?
Q192 Dr Taylor: So, to come back, there must be a formalised easier route for customers, for patients, to report?
Mr Brook: And they must be alert to what is happening and we must not just dismiss them as a signal; they are actually really big evidence.
Professor Herxheimer: I would also like to add that the reports from patients, the MHRA has no idea how to deal with them. I think it would be far better for some other body to deal with those, obviously in connection or consultation with the MHRA, but I have no confidence in the MHRA being able to analyse and understand them.
Q193 Dr Taylor: Does such a body exist?
Professor Herxheimer: No.
Q194 Dr Naysmith: Does it exist anywhere in the world?
Professor Herxheimer: Yes, in the Netherlands there is an organisation which does that, which deals with all the reports, which is independent of the regulator, which does it for the regulator, but I think that because we do not know how to set up such a body we need to do pilots of various kinds and then work out which is the most effective.
Q195 Mrs Calton: Professor Healy, in your evidence you say that the industry can engineer a clinical consensus that will favour their products and that they will shape assessment. You have already mentioned ghost-writing and some of the other issues, but how does such engineering go on beyond ghost-writing? What examples do you have?
Professor Healy: We could be here for the next hour, but let me just be very brief and focused on one issue that I have grave concerns about. At present the most commonly used anti‑psychotic in the UK is a drug called Zyprexa. What will happen is you will get a group of experts in and you can get the most disinterested experts who have no links to the pharmaceutical industry into a room to work out just what drugs we should use to treat people who have got schizophrenia, and you can, if you present them with the clinical trials that have been published, get them to agree that it would be a good idea if we replace older drugs like chlorpromazine, or whatever, that cost eighty times less than this drug, with a new drug like Zyprexa. You can do that quite easily. It just comes back to the issue of experts will say, "What we go on is the clinical trial evidence", but in actual fact what you have got here is that none of these clinical trials faithfully report the incidence of suicidal acts on this drug. Usually people like me, if we do not think the clinical trial evidence, the articles that are published in the BMJ, or elsewhere, are all that good, we used to be able to do a thing, we used to be able to go to the FDA website and get FDA reviews of these drugs. The MHRA has not got any website like this at all which would let anyone get access to any information on these drugs at all. In the case of Zyprexa, if you go to the FDA website you will find that there is not - usually, with all these drugs that are used for behavioural problems, you will get data on the number of suicides and suicide lapses that have happened in the course of the clinical trials that you cannot get in scientific literature. If you go into the bit where they have the reviews for Zyprexa you find that this section is missing completely. What this means to me is that I could not give it to you, or anyone linked to you, on an informed consent basis. This is a serious hazard of this drug: that I do not know what the hazard is. Let's say it was a huge hazard: I could say to you, "There is a huge hazard here, but I think this drug is good. We should still perhaps try using it for you, or perhaps your child. Clinical trials are happening on this drug in four‑year olds at the moment", but I have written to the Minister for Health here when it was Alan Milburn and he has been, it would seem, unable to get access to the data either. I had thought, in the usual course of events, the Minister for Health here cannot get access to the data that comes from clinical trials, but, given the clinical trials were happening here in the UK and there is requirement for informed consent for those trials, I had thought there was some onus on the Minister either to get access to the data or to stop the trials, but he did nothing. I have not actually, in essence, had a reply to the two lengthy letters that I wrote to him on the issue. So you can have a situation like this with a drug like this which becomes the most popularly used drug in its group here in the UK which grosses something like $4 billion a year for the pharmaceutical company in question happening; you know there are hazards of this order and you can still get experts, ones who have no links to the industry, into a room and get faced with the clinical trial evidence written up by the pharmaceutical companies and they will endorse the use of the drug, which is what has happened in this instance. This is why this drug is the drug that is the most used in the UK.
Mr Brook: If I may refer you, you may not have seen it - I am sure you have had a huge amount of evidence - but in the Mind evidence there was the GlaxoSmithKline sales manual for Seroxat and it was talking about moving towards the second billion; and if you actually look at that ‑ it may have been in the work for sales ‑ its strategy is all about developing new conditions for that drug and demolishing the arguments of other competitors about why their drug was not any good. Actually the evidence that was around then and now would not back up those claims, and that is a very different, very, very useful piece of information. You can get from the manufacturers their sales manual and it clearly shows that they are actually promoting the drug into new conditions and rubbishing their competitors on the basis such as it is not addictive, and yet, five years on, we have got a leaflet produced by them which says it is 25 per cent affecting people on withdrawal.
Q196 Mrs Calton: I think you have already indicated, Professor Healy, that the fact that you cannot get at the information is what is causing some of the problems. How much of a problem is it that official secrecy seems to cover over all of the information that might be there, and do you think that greater transparency would make a difference to the pharmaceutical industry's contributions to public and personal health?
Professor Healy: Yes, I think at this point the pharmaceutical companies regard the data that comes from the clinical trials as theirs, even though I do not think there is a legal basis for that. I have tried to find out what the legal basis might be, but I am not sure it is there. They regard it as theirs to be put into articles that are ghost-written up to be used to promote drugs off label for conditions that are in the process of being created, conditions like socio‑phobia, what in the US is called premenstrual dysphoric disorder and things like this. What you have is a situation where they are using the data for just the kind of purposes that circumvent the regulatory apparatus, but we cannot get access to the data.
Q197 Dr Naysmith: You have mentioned ghost-writing again, or ghost-writing has been mentioned. How does this work? In terms of footballers, famous footballers, journalists write and they stick their names on. Are you suggesting that eminent clinical scientists, academics, add their names to papers that they do not really write?
Professor Healy: My estimate is that, even in journals like the BMJ, the Lancet, the New England Journal of Medicine and JAMA, the leading journals in the field, if these articles have to do with therapeutics, with drugs, it may be worse perhaps for psychiatry than elsewhere, but I doubt it, fifty per cent of these articles are ghost-written. It may be higher.
Q198 Dr Naysmith: How would that work?
Professor Healy: It works in the sense that the industry get the data from the trials, they write the articles up, they approach authors to have their names put on the articles. These authors may not have seen the raw data at all, but they put their name to it, and they may be the most distinguished authors from the most prestigious universities. They are approached precisely because they are the most distinguished authors from the most prestigious universities.
Q199 Dr Naysmith: I must say, that is pretty disturbing stuff?
Mr Brook: I think what is also very interesting is that it has moved within the regulator, because the regulator actually receives summaries of trial data from the companies; and one of the things that struck me so strongly is that it is extremely rare that they do anything but read the summary as provided by the company and actually do not ‑ they have not got the capacity or the ability to look at the raw data themselves; so it is only when you get an issue such as the Seroxat issue and the Biox issue, or whatever, that they start to look at the raw data. So they are totally dependent on the companies whose commercial profits are made by these drugs to produce summaries of what has happened. So it is really quite an amazing situation inside the regulator as well as ghost-writing.
Q200 Dr Naysmith: I was just going to ask you another question, Professor Herxheimer, and you can say what you have got to say in reply to this as well. One of the major problems with drug promotion, you say in your written evidence, is to do with volume and intensity rather than the quality of the message. Can you just expand on that a little bit?
Professor Herxheimer: Absolutely. I think that the volume is huge. It is not just the mail and the representatives and the meetings, but it penetrates through ghost-written articles and through the consultants who are paid by companies; it creates an enveloping atmosphere that you do not know you are in. There was another point that I was going to add to what Richard Brook was saying, that the timing of the information is, of course, very much in favour of the industry. They have all the data on their new products and on all of their products, and before any independent person can get at the data it takes months or years so that independent information limps a long way behind the commercially driven information and is in a much lower volume. The funding for that is extremely small compared with the industrial funding of promotion; so that creates a very serious overwhelming imbalance, and I think that an approach to that would be to have, again, some mechanism for ensuring that independent information is properly funded and maybe there should be a levy on promotion to do that.
Q201 Mr Jones: It is going to be extremely expensive to do what Professor Herxheimer has just proposed, extremely expensive, and the level of expenditure that is in any likelihood going to be made available to this form of checking and regulating is infinitesimally small in comparison to the level of funding available on the opposite side. Since what the drugs companies wish to do is influence the industry and the Government in order to sell their product, would it not be better if, one way or another, either through the Royal Colleges, or whatever, you regulated the system whereby information was brought into the public arena, into the Royal Colleges' attention, in such a way that the only way to get that information out properly from the industry would be in order to publish data properly and that there would be an intolerance within the industry for publishing data improperly? Then you would not have to try and find some huge balancing sum of money: you will have changed the rules of the game so that the only way that the industry can play the game is according to your rules?
Professor Herxheimer: I think that the Royal Colleges are not really set up in a way that would make that straightforward. I think that by limiting the amount of promotion and taxing it so that it would have financial independent information but there would not be an end cost from that, you would have to limit this flood somehow and balance it with independent information, and that could be done in terms of money. There is another consideration, which I think is a very important one for your inquiry, which is that if we do not get it right in this country we are also harming many, many other countries which look to the UK as a lead in drug regulation; and that really is a serious mistake.
Q202 Dr Naysmith: I think we need to begin to draw to a close in a couple of minutes. The very final thing is, would each of you like to offer what you think would be an appropriate level of influence for the pharmaceutical industry that they could or should exert in order to sell its products? I will ask Professor Herxheimer first and then Mr Brook and, finally, Professor Healy.
Professor Herxheimer: I think that we would all hope for impartial statements, impartial advocacy, if such a thing is possible, whereby companies have to compare their offerings with other things that are being used for the same purpose and make those comparisons objective, clear and open to public discussion.
Mr Brook: I think for me it is quite hard to believe, given how we look at the corporate world, that we can expect in every situation pharmaceutical companies to behave in a way that I would like. So I think for me the emphasis is around regulation, and particularly around communication to patients and tough ways of looking at how pharmaceutical companies interrelate with that regulator. I think there are a whole lot of issues around communication which we have not had time to talk about today that are desperately important for patients, because they just do not receive that information. I end with a final example of why I think it is so difficult. On a working group recently on the patient information leaflet reforms we were sent some information about how the patient information leaflet should change and they were marked, "Confidential. You will be breaking the law if you release these to people." It was just about how to communicate with patients, and I think that is the strength of the pharmaceutical companies' influence at the moment within the regulator, and until we break that and create a new structure, and you have heard some ideas today, I am sure you will hear other ideas, but until we get post-licensing away from the influence of pre-licensing in particular, I think actually that is the issue, in a sense, that is how you will start to make pharmaceutical companies have the appropriate influence, by better and clear regulation.
Professor Healy: Very quickly, two points. One is that the problem you face, at least one aspect of it, is that you are trying to force a financial camel through the eye of a scientific needle, and this is always going to cause problems. The best you can do in this area, I think, is to get people to adhere to what are the norms of science, the norms of ethics, and increasing the norms of business whatever side of the political divide you come to, which are transparency ‑ this is an issue we put great store on these days - and, the other point, where there is a changing mood people are beginning to say for the first time, "If prescribers actually prescribe these drugs, are forced to prescribe these drugs, without all the information that they ought to have, this comes close to fraud." The other point is that in the Sixties when most of these drugs began to come on stream, the expectation was that physicians would play a role rather like the role they play vis-à-vis tobacco and alcohol, that they would say, "Look, you do not want to believe all the hype that you hear about these things, there may be good uses for them, but they are not always that good." At this point in time one of the biggest problems that we have in the system is the silence of physicians. What you are going to do to change that I am not sure.
Dr Naysmith: Can I thank all three of you for the evidence you have given and for the witnesses from the previous session earlier this morning. I think it has been a fascinating morning. Thank you all very much indeed.