UNCORRECTED TRANSCRIPT OF ORAL EVIDENCE To be published as HC 42-vi

House of COMMONS

MINUTES OF EVIDENCE

TAKEN BEFORE

HEALTH COMMITTEE

 

 

THE INFLUENCE OF THE PHARMACEUTICAL INDUSTRY

 

 

Thursday 3 February 2005

LORD WARNER, DR FELICITY HARVEY and DR JUNE RAINE

Evidence heard in Public Questions 911-1017

 

 

USE OF THE TRANSCRIPT

1.	This is an uncorrected transcript of evidence taken in public and reported to the House. The transcript has been placed on the internet on the authority of the Committee, and copies have been made available by the Vote Office for the use of Members and others.
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Oral Evidence

Taken before the Health Committee

on Thursday 3 February 2005

Members present

Mr David Hinchliffe, in the Chair

John Austin

Mr Keith Bradley

Mr Jon Owen Jones

Dr Doug Naysmith

Dr Richard Taylor

________________

Memoranda submitted by Department of Health and Medicines and Healthcare products Regulatory Agency

 

Examination of Witnesses

 

Witnesses: Lord Warner, a Member of the House of Lords, Parliamentary Under-Secretary of State for Health, Dr Felicity Harvey, Head of Medicines and Pharmacy and Industry Group, Department of Health and Dr June Raine, Head of Licensing Division, Medicines and Healthcare Products Regulatory Agency, examined.

Q911 Chairman: May I welcome you to this morning's sessions of the Committee and particularly welcome our witnesses for what will be, hopefully, the final session of this inquiry which seems to have gone on rather a long time, but we have found it most interesting. May I first of all thank the department once again for its co-operation with the inquiry and perhaps you would like to introduce yourself and your colleagues.

Lord Warner: I am Norman Warner; I am the Parliamentary Under-Secretary of State in the Department of Health, responsible for the area covered by the Committee's inquiry. On my left is Dr June Raine, who is the head of the Licensing Division in the MHRA and on my right is Dr Felicity Harvey, who is the head of Medicines and Pharmacy and Industry Group in the Department of Health. So we have the regulator on the left and the department's policy adviser on the right.

Q912 Chairman: May I start by asking a broad general question? If you have followed some of the developments in this inquiry, you will be aware that a number of key themes have come out of the evidence which we have taken over quite a long period of time. One of them, which in a sense perhaps informed our reasons for looking at this whole area, is that the over-reliance on medicines may well be to the detriment of our overall public health. That has come out in evidence from a range of different witnesses and organisations. What I wondered, to start off with, is how the department actually balances concerns with what we are seeing as, in a sense, the over-medicalisation of society with your role of sponsoring and encouraging and working with an industry which needs to be commercially successful?

Lord Warner: Various approaches have been taken in different countries to this particular issue. I am very struck, when I go to health minister meetings in Europe, how they are often quite detached from the industry area. You can argue whether it is a good thing or a bad thing, but it is striking that there is that difference. What I would say is that, give or take, pharmaceuticals represent about 12 per cent of the NHS budget, that sort of area. So a very large chunk of the NHS budget is going on things other than pharmaceuticals. We also have in this country a very strong use of generics by our doctors who are great users of generics, so there is a balance against what you might call the research-based industry in this area. That has been developed over the years with this strong inclination particularly of GPs to use generics wherever possible. The other thing I think I would say is that it is the responsibility of all of government to try to help research-based industries in the UK. We are dealing here with an industry which has the strongest R&D activity of UK industries. It is very strong and spends £3.5 billion a year on research, which provides a lot of high quality jobs in a knowledge-based industry. There is an important dimension there. I should say that we have kept the balance pretty well and I am not making a party political point here. I think that under successive governments, the balance has been struck between having a health department which has a responsibility as a sponsor department for the industry and is also safeguarding the patients' interests and the NHS interests through both its regulation and, if you like, its purchasing power. The UK is unique in having a pharmaceutical price regulation scheme on a voluntary basis; it may not always seem voluntary as you are going through some of the negotiations, so I am told, but it is a voluntary agreement. The last one did produce a very substantial reduction in prices for the NHS which does suggest that we are actually able to achieve this balance between being a sponsor of the industry and getting the best value for the NHS.

Q913 Chairman: One of the things which have struck me, in looking at the health service over very many years, is that we have focused very much on a curative approach, on initiatives to do with hospitals and the choice initiative is a very good example now where it is about where you choose to go for your treatment. Only very belatedly have we actually looked seriously at developing a much more radical public health agenda. Am I wrong in getting the impression that the industry has perhaps skewed our thinking, our approach to health, because of its own commercial interests? It is in their interest to create in society an expectation that we can get a cure for every possible problem and there is not a lot of money to be made out of preventive approaches which are implicit within the Public Health White Paper.

Lord Warner: There is a balance to be struck here because there is a short-term/longer-term issue. Clearly the public health agenda is extremely important but as you take forward the public health agenda, and the government's White Paper on choosing health sets out a very clear and dynamic strategy for helping deal with many of what I may describe as the lifestyle choices that people need to make in order to maintain good health in their communities, we are also faced as a society, and the government has to respond to that, with the fact that in the here and now a very large number of people have painful, deadly, unpleasant conditions where we need the best therapies we can get to respond to those conditions; we need to help provide healthcare professionals with, so to speak, the tools to do their job, so we do need these therapies. We have also seen a growing flow of therapies which enable you to use medication without becoming an in-patient; so you can actually make the health response much less institutional and much more able to enable people to cope with chronic disease conditions without emergency episodes in living in their own home with the appropriate professional support. So there is a balance to be struck, but I would agree with you that probably historically we have been a bit slow to engage with the public health agenda.

Q914 Chairman: One of the other themes which has been within this inquiry quite clearly is the way in which we have seen a pattern of medicines, which have been initially hailed as breakthroughs, being widely promoted for their positives, either being withdrawn or later having had serious questions over their safety profile. I wonder whether you feel that the controversy around medicines such as Seroxat, Vioxx and Celebrex indicate that there is perhaps a problem with the licensing of potential unsafe medicines.

Lord Warner: Whatever pharmaceutical we are talking about, most of them have some degree of downside as well as an upside and the whole point of clinical trials is to try to get to the bottom of that risk benefit balance on particular drugs. This country has followed the lead of other countries as well of having basically a three clinical trial stage system of licensing and an independent regulator trying to get the best data that it can before giving licensing approval. It has always been the case, and it has become more robust, that there is a degree of post-licensing monitoring and surveillance of particular products, so that when problems are identified, whether it is adverse reactions notified through the yellow card system, whether it is new clinical trials data or whatever, there is a process by which the regulator can conduct further analysis. There is a good track record on the part of the Committee on Safety of Medicines of taking seriously that data which shows after licensing there can be a problem. You could argue that some of the high profile examples which you have mentioned are demonstrations that the licensing system does work, that there is a good post-licensing system for picking up problem areas and dealing with them. What I should also say is that if we are absolutely frank, we may have been a bit slow in the past in making sure that the regulatory system was as transparent as possible in actually bringing information into the public arena at an early enough stage and I arrived in this job at the same time, pretty well, as the National Audit Office report and the PAC report on the MHRA. There were some pretty valid comments there about transparency, public communication, whether we had done enough to demonstrate the independence and effectiveness of the regulatory system. I do not think there was a fundamental problem, but we have tried to take a number of measures which I think the Committee is aware of, to try to improve that transparency. Certainly there is an area on which we shall continue to need to work away with the industry and that is the whole area of a public register of clinical trials and publication of all clinical trials data, so that it is in the public arena when that information is available in a company or wherever.

Q915 Chairman: One of the underlying themes of the inquiry has been a rather low opinion of the MHRA from a number of witnesses consistently expressing concerns. Your evidence from the department is neutral on that organisation. You have just referred to transparency and the potential for further change. Do you feel that other reforms are needed to address a number of the concerns that we have had put to us about the regulatory regime?

Lord Warner: It is worth just going back to the NAO report, because whatever else one may think, one would not accuse the NAO of being in the pockets of either government or the industry. They found that the MHRA had made a significant contribution to public health protection through its regulation of medicines and they did not find any evidence that it was too close to the industry. That was the NAO speaking, not me. Certainly, they made a number of recommendations for improving the perceptions around whether the regulation was as transparent as might be. My own frank assessment is that its predecessor body was very professional sound, though probably a bit lacking in communicating and providing information in the public arena which built public confidence in some of its decision making. That is why we have taken a very hard look at the committee structure and, as you know, we shall be creating a new commission on human medicines which mergers the Medicines Commission and the Committee on Safety of Medicines. We are going to require the chairs and members of the commission and the new statutory committees to have no financial interest in the industry, a stronger code of practice on declarations of interest, we have reviewed the yellow card scheme where we think patients ought to be given the ability to report adverse reactions themselves, so we have taken a number of measures to make this more patient conscious so the patients can play a bigger part in some of the risk benefit judgments which actually have to be made in this particular area.

Q916 Mr Jones: The Chairman raised problems developing, three medicines that he mentioned - Seroxat, Vioxx and Celebrex. On Vioxx, there is a problem area now in that you have clear evidence that there are potential risks to some patients using Vioxx, on the other hand, we have a very large number of people in the country who have been using Vioxx for a long period of time without any adverse effects. If the drug is withdrawn, and presumably these people are then prescribed a different drug, for those people what we are effectively doing is increasing their risks because there is a risk inherent with every drug. They have been using the drug without adverse effect and now they are going to be told they cannot use that, they have to use a different one and they do not know whether there is an adverse effect. That is a very difficult issue, but I should be interested in what you think. Is there not a case to be made for saying "We withdraw the drug and we will not prescribe it to anyone new, but those people who are currently using the drug should be able to continue to use it".

Lord Warner: This is a very difficult issue. That in a sense is why we have an independent regulatory body trying to bring together all the evidence to see where the balance of advantage lies and the balance of advantage often lies in a different position on different products. You put the point very well in the way you described that as the almost perpetual dilemma for drug regulators, either in this country or in other countries: how do you get the evidence to strike the right balance? One could repeat some of your arguments for a number of other products as well in exactly the same sorts of terms. I saw on the television the other night with the phased withdrawal from Coproxamol that there was a long-term user of Coproxamol who was not terribly pleased that this was happening. I do think it is a bit of a dilemma; I do not think there is any easy answer. There are some issues, which we have begun to think about, about whether the present system is as sophisticated as it might be for regulation and whether you talk about some kind of provisional licensing at a stage after stage three clinical trials or whether you talk about more robust post-licensing surveillance or some kind of restrictions around the class of doctors who could prescribe particular products for a period of time, so that you get a wider usage. I do not know, but there are issues there which are beginning to be discussed where we do need to do some more work within a European framework and with other regulators.

Q917 Mr Bradley: The World Health Organisation recommends that all countries should have a national medicines policy. What are your views on introducing one here, together with a dedicated committee to oversee the quality of use of medicines?

Lord Warner: We do have pretty good data and monitoring of the use of medicines. I know, for example, that there has been some interest in iatrogenic effects of drugs, where the MHRA actually did their own study in this particular area. I do not want to appear complacent, but I think we do have a pretty good system of seeing how drugs are being used, seeing how prescribing is going, whether the balance is right between new drugs, research-based drugs and generics and so forth. We are always going to be in a situation where science to some extent drives the agenda; there will be new discoveries which will drive an agenda and will come up out of the science community for any country. There is a lot in what the WHO are saying and one of the things which we are going to do is to see whether we cannot have, what we are calling at the moment, a futures forum, which starts to look ahead, tries to be a bit more anticipatory about some of the areas where we might try to get the science applied faster where there is clear human need. What we have in mind here is that the UK clinical research collaboration, which was set up by government about a year ago, which brings together industry, the research community, the charitable sector, patient interest, we might ask them on a regular basis to discuss where medicines policy might be directed more and relate it more to the progress of science in scientific knowledge. I do not know whether that deals with the kinds of things you have in mind.

Q918 Mr Bradley: Yes. When we were in Australia, we saw the value of having a national medicines policy with broadly based interest groups involved in that process, particularly consumers and users. We were struck that that took a much more holistic approach to medicines in terms of health outcomes as well as economic objectives and the World Health Organisation recommends that looking at it in that way, in the national sense, is a more effective way of ensuring the value of the medicines themselves.

Lord Warner: It is a very helpful suggestion. It is similar to the kind of thinking that has been going through our own minds and I shall certainly take a closer look at the Australian experience there and see if we can learn from that as we take this idea of a futures forum further forward. The idea seems to me a sound one and I should certainly want to look at it very carefully to see whether we can build on that.

Mr Bradley: I shall come out with you as I should welcome a return visit.

Q919 Dr Taylor: May I go back to the question of independence of the regulatory agency, which you have already talked about? We are told that the MHRA is one of only two European agencies for whom the operation of the medicines regulatory system is funded entirely by fees derived from services to industry and many people have implied to us that it must be incredibly difficult actually to protect the public from unsafe medicines when you are being paid by the very people who are producing those compounds. How do you rate the independence? How do you ensure it when they are being paid by the very people who they are trying to regulate?

Lord Warner: Just dealing with the European situation first of all, virtually all the European regulatory agencies have a significant contribution in terms of income from the industry that they are regulating; there is nothing very unusual about that. If you go to Sweden, I think you will find it is about 95 per cent, if you go to the Netherlands, you will find it is 100 per cent, so we are not that out of line.

Q920 Dr Taylor: Are you saying that the facts we have been given are probably not correct?

Lord Warner: I am happy to go back and check. I have two colleagues here who are perfectly free to correct their minister if he has got it wrong and I shall not be embarrassed, but my understanding is that it is about 95 per cent in Sweden and it is about 100 per cent in the Netherlands. They are nodding, so I think it is probably OK. What I was also going to say is that it is just worth thinking back to the dim and distant past when there was significant grant aid from the government to a predecessor body. That was changed because the backlog of licensing applications was enormous, because the income fees did not seem to be very buoyant in terms of maintaining the capacity of the regulator to deal with the flow of new drugs for licensing. Under a previous government the move to a trading basis was to generate buoyancy in the fee income. They then kept pace with the volume of work that was coming into the regulator. That is an important consideration. I go back to what I said about the NAO, there is no evidence that this form of funding has in any way skewed the decision making of the agency. It has also separated operationally within the agency pharmaco-vigilance from the licensing; it has separated that work under the chief executive, so you do not have the same people doing the licensing as are doing the pharmaco-vigilance in post-licensing. Dr Jean Raine is actually the head of the post licensing and she has nothing to do with the licensing applications themselves.

Q921 Dr Taylor: When the regulatory system came in - and I am old enough to remember the problems with thalidomide and it came in after the thalidomide episode - was it funded by industry right from the start? Has it always been funded by industry? What happened initially?

Lord Warner: I do not know whether my historians on my left and right will be able to answer that precisely?

Dr Raine: Yes, the initial operations were not funded by industry; this was introduced in 1989.

Q922 Dr Taylor: So why does it change?

Dr Raine: For the precise reasons that the minister has explained, that the operation then was not capable of delivering new licences, delivering new medicines for the benefits they bring in a way that was demanded; it could not meet supply and demand. The funding enables us to match resources incoming to the staff and other resources that are needed to deliver new medicines promptly.

Q923 Dr Taylor: So what are saying is that the only way of getting enough money into a regulatory system is from the industry. There is no other way.

Lord Warner: I do not think we are saying that. We are saying that history has shown that using government grant did not produce buoyant income which enabled the regulatory body to cope with the flow of applications for licences.

Q924 Dr Taylor: That must have been because the government grant was not big enough.

Lord Warner: That could well be the case. If you go from where you are now, whichever government is in office, there is a finite sum of money for healthcare. You have a judgment now: do you want, for no good grounds, there is no evidence base that the regulators are actually skewed in their judgment over the licensing or post-licensing surveillance. There is no evidence, so you would have to take however many millions away from somewhere else in the NHS to fund the regulator.

Dr Taylor: I am only trying to establish that with the amount of money that there is available from government sources, there is not enough to do this, so the only source it can come from is industry.

Q925 Chairman: Just to clarify the historic background to this, may I ask Dr Raine a question? You may not know the answer and it is probably an unfair question. Do you know, when this change took place, how much more money was proportionately able to be brought into this process than was previously available from government? Have you any idea?

Dr Raine: In terms of funding? I think it would have gone to a figure of around £30 million per annum to resource the whole of the agency, of course it has gone up since then.

Q926 Chairman: What was it previously?

Dr Raine: I do not have an overall figure, but I do know that a new drug costs about £250 to get the licence through and that was not sufficient to recruit and retain the numbers of staff. There was therefore a delay of around three years in some cases before getting a new drug out to patients who needed of it.

Q927 Chairman: It would be very helpful, if it were possible, for us to have any information on the background and the proportionate increase as a consequence of these changes. It is a very important area.

Lord Warner: We are very happy to provide the historical context for this, but it was basically driven by this huge backlog.

Q928 Dr Taylor: Did you say that the total cost was £250.

Dr Raine: No, that was the fee that was charged.

Q929 Dr Taylor: The fee that was charged was £250?

Dr Raine: For a new drug.

Q930 Dr Taylor: That is staggering. That would be helpful.

Dr Harvey: In fact, in terms of the approach of having the regulator with fees to those who are being regulated, this is actually the approach which is taken in many bodies across government. The MHRA clearly is a regulator for medicines, but there is exactly a similar approach adopted in many regulators that the government has right the way across government. It is not an unusual occurrence.

Q931 Dr Taylor: That is very helpful; thank you. May I go on to transparency, which we have already touched on a little bit? We are pleased about the clinical trials register and that all the data from that is going to be openly posted. Will you be suggesting that the MHRA should make the data it receives from drug firms open to the public?

Lord Warner: There are two aspects to this. There is the obligation on the companies which certainly the ABPI have accepted, that they should be publishing clinical trials data in the public arena anyway. They are under a legal obligation to provide information to the regulator anyway which relates to either an application for a licence or which relates to a licensed product. So that, one way or another, will get into the public arena. What we are keen to do and it was done very well by the Committee on Safety of Medicines in the case of Seroxat for example and selective serotonin reuptake inhibitors (SSRIs), is to make sure that those decisions have the supporting evidence put in the public arena, which is a slightly different issue from publishing clinical trials. Instead of the regulator simply saying "We think the risk benefit balance has changed, therefore we think a particular product should be withdrawn" or not, as the case may be, it would actually put the evidence behind its decision much more fully in the public arena. I cite the SSRIs as the example where I think that pattern is established. Certainly I am very keen and the agency knows that the government is keen, that that information is put in the public arena so there is no doubt about why the balance was struck. It relates back to an earlier question about the difficulty of some of these judgments which have to be made. People will be more convinced that the judgments have been fairly made, if the supporting evidence for their judgment is clearly in the public arena.

Q932 Dr Taylor: That is very encouraging. Does that mean, with the Freedom of Information Act (FoI), that will be interpreted literally and the MHRA will have to make available the sort of information that is already available in the United States?

Lord Warner: This is better linked to a decision-making process. The short answer is, in all probability, yes. I am not saying that we feel you need FoI to drag the information out of the agency. I am saying that it is in our interest and the agency's interest to publish the data which they relied on in forming their judgment about whether or not to withdraw a product which had already been licensed when there were adverse consequences.

Q933 Dr Taylor: We are told as well that in the States advisory committees actually sit in public, so everything is known. Is there going to be any move towards that?

Lord Warner: We have no plans at the moment. These are always difficult issues here about whether people feel inhibited in their free and frank discussion about information in those particular areas. It is an issue we could consider, but I would not want to make any promises. We do have a situation here where we are moving these committees to have more patient representatives in them. We need to take a careful look at whether that would have advantages or whether it might actually, in some cases, inhibit people's frank analysis and comments in some of these areas.

Q934 Dr Taylor: How will you be supporting extra patient representatives? How are you going to encourage them to make that possible and to make these representatives really effective? We have heard about the NICE (National Institute for Clinical Excellence) citizens' council and we heard early on the plans that was making. We actually have not heard anything about how successful that has been. How are you going to empower these people and put them in so that they really can make a difference to the process?

Lord Warner: It is a very fair point. In other fields there is always a great risk that, in these sorts of circumstances, people become token appointments and get isolated. We are well seized of the need to have a patient support mechanism. I think where we are likely to be is having some kind of over-arching patient advisory body and we actually have patient support arrangements for the people who are on the particular committees. We are very clear that there should not be single patient appointments, that there should not be just one patient representative on a committee. There is good evidence around in other fields that that is not a very successful way to get the best out of patients. We are working with Mr Harry Caton who is the department's adviser on patient issues to see what support mechanisms we need to put in place to make this a success. We accept the point that you are making in your question, that it needs to be watched very carefully.

Q935 Dr Taylor: From what you have said, can we take it that you will ensure that the British public gets the same access to policies and resources that the people in the States have?

Lord Warner: We shall probably do things slightly differently. I am certainly not going to go on the record as saying I am going to copy everything that is actually done within the framework of the FDA. We will learn from that.

Q936 Dr Taylor: But you will aim for the same degree of discussion.

Lord Warner: We are aiming for transparency in this area in order really to enable the regulator to demonstrate that their decisions are well founded. The point I would make is that it is not in anybody's interests to create a climate in which regulators make decision which are then called into question because there is not enough transparency about the way that decision---

Q937 Dr Taylor: People need to see both sides of the argument and they need to hear the dissenting voices as well as the supporting voices.

Lord Warner: Absolutely. It is all part of this business of improving public understanding of the difficult judgments that have been made, which have been touched on earlier, on some of these products. Getting the right balance on risk and benefit is very difficult in some of these areas and the more we can have information demonstrating this in the public arena, the better it will be for everybody.

Q938 Mr Jones: I think the committee were very pleased to hear what you said about publishing data and allowing the public to see what the information is. It is likely to improve decision making, not least, I should imagine, probably their competitors would be interested to ensure that are no glaring faults or missed information in the data. In the absence of that up to now, the MHRA's reliance on company analysis and summaries of research findings clearly is not justified, at least in every case; I can see that it was not justified with Seroxat for example.

Lord Warner: You have mentioned a particular product, so I am going to turn to the person who led the work in this particular area.

Dr Raine: Perhaps to deal first with the point about the use of summaries. Summary is perhaps a misnomer: these are very large and very detailed analyses of what would be otherwise vast amounts of original patient data. It is the standard practice in European drug regulation, indeed regulation worldwide, to look at analyses and then to drill into the detail that is needed, as it is needed. When we say analyses, we are talking 200 dossiers for an average type of new drug, so to say "summary" is perhaps misleading your thinking.

Q939 Mr Jones: I do not want to go into too much detail, but with that particular drug you were not provided with all the relevant information, were you?

Dr Raine: We were certainly provided with all the information in order to make a risk benefit judgment at the time of licensing. Clearly, when the review was conducted which was published in December, we had access to a far wider body of information but in addition we carried out re-analyses of original trials. It has been done in other situations too, with Epogam, which the Committee has mentioned in the past, we went back to original data. This is the way that regulation works and it is quite proper to operate it in that way. The decision which was published in relation to Seroxat last December took account of population studies, ADR reports, patient experience, as well as original clinical trial data re-analyses in order to make the best balanced judgment that could be made and indeed it is now in the public domain.

Q940 Mr Jones: Are you saying that you, as a body, were given all the information that was available for you to make a reasonable decision at the time you made it?

Dr Raine: Yes.

Q941 Mr Jones: So there was no fault on your side and no fault on the company's side either then?

Dr Raine: Going back to 1990, the data were provided according to the guidance operating at that time to enable a robust decision on risk and benefit in 1990.

Q942 Mr Jones: 1990. What has happened since?

Dr Raine: Since then, as is normal for medicines, a vast amount of information is gained about clinical use, other studies are conducted in other indications and, as we have stressed, in this case, there was a substantial body of information available from patients themselves. To make a re-visited risk benefit judgment, all of that was taken into account.

Q943 Mr Jones: You do not think you could have improved the situation then at the time?

Dr Raine: In 1990 the produced information reflected the understanding of the balance of risks and benefits and the advice of the Committee on Safety of Medicines at that time.

Q944 Mr Jones: May I move on? In the absence of near certain evidence that the regulators tend not to issue formal warnings of risk, are you satisfied the regulators effectively communicate uncertainties of risk to the users?

Lord Warner: I suppose the documents the users get are the patient information leaflets, which are themselves modified over time; as new evidences comes around people do revise the patient information leaflet. It is probably the thing on which patients rely most. If you say to me "Are patient information leaflets perfect in every way?" the short answer is that they are not and that is why there is new legislation coming through Europe to ensure that patient information leaflets are themselves produced with much more user involvement in their production. As I recall, I will get my colleagues just to check, that new legislation comes into operation in October.

Dr Raine: Perhaps I might just expand on that. The new requirement that medicines information for patients is tested in the population who are going to be using that medicine was in fact introduced early, so it will become operational from 1 July.

Lord Warner: We are trying to construct a situation in which the document which is the lead document for patients about particular medicines is framed in a way which is most useful to patients. I suspect what lies behind your question is: is it always easy to tell from the document what the real risk benefit to particular people is? I think that is a perfectly fair point to be made and that is why we have to try to improve the quality of the presentation of information in those leaflets. I think you will find that somewhere in each of those leaflets the danger signals are signalled. The question is whether they are signalled in a way which is most helpful or whether they could be made more helpful to patients on a particular product. We have already published a leaflet from the new group that we have set up in this area to try to help patients themselves understand risk issues.

Q945 Mr Jones: What about information given to the prescribers? Is it made clear to the prescribers that this product has this potentially beneficial effect, but that there is a range of unknowns and possibilities that it may have?

Lord Warner: Well of course there is a very vast array of information given to prescribers. There is a national prescribing centre and various bulletins are sent to prescribers. The very fact that we have such a high use of generics suggests that prescribers are, on the whole, pretty well-informed about the products.

Q946 Mr Jones: As we have had evidence before, the access providers get to information about new drugs comes overwhelmingly from the people who are producing the drugs. Therefore, it is unlikely that the person who is selling the drug is going to highlight what potential risks there would be to that product.

Dr Raine: Perhaps just a word of clarification. The information that the company provides is very strictly controlled in law. The terms of the marketing authorisation can include the document called the summary of product characteristics, which is an evidence-based document on which we seek advice from the Committee on Safety of Medicines. The controls on any communication are that they must strictly adhere to those terms. So that is the starting point for advice to the user or the prescriber which is an evidence-based document.

Dr Harvey: May I also add that the National Prescribing Centre does indeed send bulletins to doctors, not just for drugs which are quite a long time post-licence, but it often sends out bulletins at the time, or very shortly after licensing of new drugs, which deal with their clinical and their cost effectiveness and it also sends bulletins through for drugs which are on the horizon, which are likely to be coming to market shortly. So, in fact, prescribers do have information not just from the pharmaceutical industry, but also from other independent sources as well.

Q947 Dr Taylor: May I just follow that up absolutely specifically. To take Vioxx as an example, on the day of release I am sure there was a lot of material, albeit controlled, from the makers. What, for example, would an ordinary GP have had to tell him why to be cautious about Vioxx on the very day that it was released, remembering that the GP probably will not look up the BNF every day, will not read the Drug and Therapeutics Bulletin every day? What would he have had in practice to compete with the stuff from the drug industries?

Dr Raine: May I describe what happened on 13 September? It would perhaps help the Committee to know that this was a voluntary decision by the company.

Q948 Dr Taylor: I mean at the moment of marketing, not at the moment when it was decided to put restrictions on it. What I am trying to get at is how we could prevent GPs, who are the bulk of prescribers, going into a new drug with tremendous enthusiasm right at the beginning when the side-effect profile, the problems, cannot be known. I think the minister said that there were thoughts about limiting the numbers of doctors that could prescribe new drugs. What I am getting at is, what actual information, other than from the pharmaceutical industry, would a practicing GP have had about Vioxx on the day that it was liberated to warn him to be a bit careful and not to use it as the first choice non-steroidal anti inflammatory drug on a patient?

Lord Warner: It is almost impossible to answer your very specific question about one particular day, when Vioxx was put in the public arena. What is a fairer way of trying to answer your question is to go through all the sources of advice and information that are actually to GPs which cover all new products. I do not want to sound as though I am reading out a shopping list, but it is important to realise what these other sources are. There are 1,200 NHS prescribing advisers, mainly pharmacists, there are area prescribing committees, there is the BNF, there is NICE advice on particular products, admittedly not on the day that you are mentioning, there is the National Prescribing Centre which sends out MeReC bulletins, newsletters, there is the monthly Drug and Therapeutics Bulletin published by the Consumers' Association, there is a vast array of information. With respect, Dr Taylor, that does cover things like Vioxx very close to the point when they are being, as you put it, liberated for the GP.

Q949 Dr Taylor: We do know that GPs are faced with a vast amount of information. What I am trying to get at is whether there would be a mechanism for a specific very brief message of caution, or whatever, when any new drug which is potentially an advance is liberated, absolutely obligatory reading somehow to advise caution, so that the things are not thrown around as freely as Vioxx was?

Lord Warner: I am certainly happy to look at the issue, but my experience of GPs, and I would certainly defer to you in this particular area, but my experience of GPs is that they take their information from sources that they trust and we do have a black triangle system which does also give alerts about being cautious in particular areas.

Chairman: May I just make a point? In a sense I am trespassing on an area which Richard wants to raise anyway later on. Last week some of us from the Committee went to meet the Use of Medicines Committee at UCLH and we were actually very, very impressed by the work that they were doing, but struck by the fact that a similar mechanism did not exist within primary care where the industry have direct access probably more often to the GPs than happened in a hospital environment. There was not that mechanism for actually looking very carefully at what was being prescribed and that was an area where we felt there was a big gap.

Q950 Dr Taylor: Yes, we were incredibly impressed with the method of control of prescribing at UCH and the spin-off onto local PCTs. They certainly had controlled the use of some of these new drugs and we really wondered whether there could be some standardisation of drug usage committees throughout the NHS because where you have a very good one, at UCH, it overspills into the hospital prescribing and the local PCT prescribing and this would seem to us to be quite as important as things like ethics committees, which are standardised, and could make a huge contribution. I think this would perhaps lead to the more rational use of some of the new drugs as they come out. It is really a question of the importance of these committees when they really work and how the government could support these.

Dr Harvey: We do have prescribing advisers at PCT level, but the area prescribing committees are very much around looking at the use of drugs across the primary and secondary care interface and you would expect within those committees that you would have representation from the various NHS trusts within that area, as well as the PCTs, to look at the sort of prescribing habits they have and to look to see what their general policy across the piece is, so I think part of that is possibly covered within the area prescribing committees at the moment. It is actually also fair to say there was a report Primary Care Prescribing a bulletin for primary care trusts by the Audit Commission back in 2003 and they looked at some of the activities that primary care trusts are taking forward at the moment around prescribing. As you said, in many cases GPs directly see pharmaceutical representatives, but in some PCTs - and they gave an example of somewhere with a slightly different approach - they actually went to an information centre where that information was then distributed. So there are different mechanisms at PCT level, but the area prescribing committees and indeed the prescribing advisers are very important in giving help to prescribers within primary care.

Chairman: It is probably important to make the point that we did have contact with a GP who was on this particular committee; although it was hospital based of course the PCT was represented. The picture we got was very much of a concern within the hospital environment that patients were being admitted who had been using products that certainly had been looked at by the committee and not seen to be particularly helpful for the condition from which they were suffering. So there was a concern about direct access to GPs and the impact that was having. That was the evidence which came over quite strongly.

Q951 Dr Taylor: Another point from that meeting. They obviously had a very effective formulary and I do not mean anything like the British National Formulary, I mean really just a list of the sorts of things that they would sanction the prescribing of, and it seems to be fairly ridiculous that every PCT, every trust works on their own formulary. Why could there not be a much wider-ranging formulary agreed across many PCTs, across many strategic health authorities and many trusts, rather than everybody trying to invent their own wheel?

Lord Warner: Of course NICE guidelines do that, but they are very specific to specific products, are they not?

Q952 Dr Taylor: They only come in two years after they are put NICE and there is a very limited range.

Lord Warner: May I ask Dr Raine to try to explain the black triangle system, because I think the black triangle system does actually deal with some of the concerns that you actually have.

Dr Taylor: Yes, that was explained to us actually.

Q953 Mr Jones: From the black triangle, can I move to the yellow card, because I think all the evidence we have received says that the yellow card system does not work. So, minister, what are you going to do about it?

Lord Warner: All the evidence I have suggests that the yellow card system does work, but could be improved, so we are probably coming at this from a slightly different position, if I may put it that way. We did have a review of the yellow card system by Dr Jeremy Metters, which was published last May or June and that was looking at several things. Essentially what he was saying was that, with appropriate safeguards, the information that was available from the yellow card system should be available to researchers much more easily, so that became a resource there. I do not think there was any evidence from that inquiry or from any other work that I have seen that the yellow card system did not feed in as an alert to ensure that the regulator accumulated information about particular areas causing concern. What it did identify was, in a sense, a gap in the ability of patients to be able to fill in their own yellow cards and send in direct to the regulator, their own perceptions of adverse reactions. I think there is a misunderstanding to some extent about the yellow card system. Every time you get a yellow card, it is not conclusive evidence that a particular product is causing a particular reaction in a particular person. It is saying that a particular person has had some reaction.

Q954 Mr Jones: I understand that.

Lord Warner: I get a fairly substantial parliamentary correspondence on the subject of yellow cards.

Q955 Mr Jones: Not from me. I understand that.

Lord Warner: I think it is important. I do not think it is always fully understood.

Q956 Mr Jones: Well I think we understand it, but yes, obviously each individual yellow card does not really tell you a great deal in itself. Where it becomes useful is if you have a substantial basis of statistical evidence from a large number of people who are saying similar things. The reason the yellow card system does not work is that you do not have enough information coming in from them; you do not have enough yellow cards being reported to you.

Lord Warner: Volume does not tell you necessarily to ring the alarm bell. We accept that we need to change the system so that it is easier for patients to complete their own yellow cards and make their own notifications and that is why we have, and I will ask Dr Raine to give you a little more detail, a pilot which we are now running in this particular area, which does try to address some of those concerns, certainly in terms of getting a faster, higher volume, patient response.

Dr Raine: Yes, I would reinforce what the minister has said. Every adverse reaction does not need to be reported in order to generate signals. The importance is to have enough and to have them in time to act quickly. That is why, over the years, we have expanded the reporting base from the original doctors and dentists and coroners to include pharmacists and nurses and now patients. It is the breadth of capture that we need, plus the facilitation of their input via electronic, via a number of mechanisms which are currently being piloted as the minister says. We now have paper reporting, we have reporting via the internet for patients as of the 17 January and I am very pleased to say we are up to about 35 reports now from patients and this is all vitally important in picking up those signals, but it is only a part of the comprehensive programme of pharmaco-vigilance that the MHRA operates. It is the initial trigger for a number of actions that will strengthen, confirm, or refute the signal and enable us to take prompt regulatory action and the tough decisions which need to be taken to protect the public.

Q957 Mr Jones: Did you say you are up to 35 reports from patients?

Dr Raine: From patients in a matter of a week or two, yes.

Q958 Dr Naysmith: I want to explore a little bit what Richard was exploring a minute or two ago, but from a slightly different angle. We have had a lot of evidence that GPs can sometimes be a bit profligate in their prescribing of drugs and that that is probably related to drug companies targeting GPs in different ways. We have heard evidence too that, increasingly, nurses are being targeted now that they have prescribing powers. As you say, there is lots of information about: there are the black triangles and there are the NICE reports and there is the Drug and Therapeutics Bulletin and all that sort of thing. However, in the midst of this comes nice glossy advertising from drug companies which can be used and busy GPs might think this is the right thing, this tells them all they need to know. I know that is not what the best GPs will do, but it certainly does happen with some and from your answers so far it sounds to me as though this does not really concern you very much, the role of advertising coming from the producers in the midst of all this information. You seem to think that because all the other information is there, then it does not matter too much that there is this glossy stuff produced by the drug companies.

Lord Warner: I certainly would not want to convey the sense that I do not take that point seriously. I think I was trying to say that there is another side of the equation which is the volume of other sources of information to GPs that actually exist.

Q959 Dr Naysmith: My point is that probably the material coming from drug companies outweighs all of that information. I know, as Dr Raine told us, there are regulations about what can be said and it is controlled but ...

Lord Warner: May I just give you a couple of statistics which I think slightly call into question the idea that GPs are sitting there and just simply lapping up everything which is put to them by a drug company?

Q960 Dr Naysmith: I do not want to give that impression.

Lord Warner: No, no, but it is important. It is just worth bearing in mind that the national average for generic prescribing is round about 78 per cent. That figure itself is a telling figure in my view, compared with many other countries, which does suggest that the GPs do take a great deal of notice of some of these other sources of information. It is also worth bearing in mind my second statistic. The Audit Commission did a study a couple of years ago and they estimated that wasteful prescribing was round about two per cent of prescription expenditure in 2003 and that compared with a 1994 estimate of 13 per cent. So the Audit Commission, which again is pretty independent, were saying that wasteful prescribing had dropped significantly in ten years. I would not want to claim that there is no GP in this country who may not be unreasonably influenced by some of the literature, but I think there are quite a lot of powerful checks and balances in that, and there is also a good deal of self-regulation and control over the way the pharmaceutical industry itself can produce its own literature. I do not know whether Dr Raine would like to give a couple of examples.

Q961 Dr Naysmith: Just before that, minister, might I ask you whether you think the majority of drug adverts encourage the rational use of medicines by presenting information objectively and without exaggerating the properties of the advertised product, which is what it is supposed to be? Do you think that is true?

Lord Warner: We would be catching a very large number of people out if it were true. I would say that the number of examples where we have had concerns is relatively small and that is why I was going to get Dr Raine to talk about the systems we have for checking that kind of behaviour.

Dr Raine: Certainly the self-regulatory system is one which has stood the test of time, but the MHRA is ready to back up with investigation and enforcement, any complaint, any problem advert which is discovered on scrutiny and also increasingly by pre-vetting advertising before it is issued. In the light of ongoing vigilance in the area, we have overhauled our systems in the last couple of years to focus on pre-vetting precisely because of the concerns that the Committee has expressed, that preventing misleading adverts going out is actually where we ought to be, rather than catching them once they have gone. I am pleased to say that the number of pre-vetted adverts has been steadily increasing since we did that.

Q962 Dr Naysmith: We have had evidence that it sometimes takes a long time after a component is made for it to be withdrawn. Are you saying that is now a thing of the past and will not happen any more?

Dr Raine: I can say that with confidence. We now have very tight time targets in place, with the team which operates here to act in response to complaints, to have misleading advertising withdrawn.

Q963 Dr Naysmith: In the very complex negotiations that go on for determining the price, there is an allowance for promotion, is there not, in the formula which enables companies to benefit? That is so, is it not?

Lord Warner: Within the PPRS system?

Q964 Dr Naysmith: Yes.

Lord Warner: Yes, that is correct.

Q965 Dr Naysmith: Do you ever use that as any kind of mechanism for saying someone has a bad record? Can that be done? Can individual companies be treated in that way? You are saying there is no bad record any more, but just if there were?

Lord Warner: No, I am not saying there are no errors, no bad behaviour at all. Not everybody is a saint in this particular area, if I may put it that way. What I think I am saying and I think Dr Raine was saying is that we have certainly tightened up the system for dealing with complaints, so they are dealt with more speedily. I think the Committee wanted to have, and we shall make it available to you, the data on the MHRA staff who are dealing with this particular area. We brought copies along and I will not go through what is in that, we will give that to you. It sets out which particular staff, what their qualifications and experience are, and I think that will be helpful to the Committee to have that. We have focused much more on pre-vetting as Dr Raine was saying. No human system is perfect in all respects, but it is a stronger version of what was there before and we do think we are hitting the nail on the head much more than may have been the case in the past. I certainly do not want to give the impression that we are complacent about this and it is an area which does require continuing vigilance.

Q966 Dr Naysmith: That would deal with the quality aspect, what is said in adverts. What about the quantity, which I was raising at the beginning in terms of the amount of material that comes from the producers of drugs versus the very small amount of information that comes from you, I suspect?

Lord Warner: I am just going to ask Dr Harvey to say something about the way this gets taken account of in the PPRS system which I think is where we left that.

Q967 Dr Naysmith: That would be one mechanism of dealing with it, if someone transgressed.

Lord Warner: Yes.

Dr Harvey: In fact within the new PPRS scheme which came into force on 1 January of this year, the 2005 agreement, the sales allowance of the 1990 scheme is now the marketing allowance and that does deal with advertising literature etcetera; there is also an information allowance in a similar manner to the information allowance within the 1999 scheme. It is fair to say that in terms of the allowances within the PPRS scheme, there is a reduction on the promotion side and more of an increase in terms of the allowances around the actual information itself, although the overall allowance, if you take it all together, is the same as it was in the 1999 scheme.

Q968 Dr Naysmith: How do you measure the amount of promotion that goes on, or is it just assumed this is a kind of chunk that everybody takes, a box is taken, you have promoted therefore you get the allowance.

Dr Harvey: In terms of the PPRS itself, the PPRS, as you probably know, works in terms of annual financial returns which companies send to the department on a confidential basis which deal with the various allowances that they have, but also in terms of how they are making the, what is now, seven per cent reduction in prices across their portfolio of branded medicine to the NHS. Those are looked at, those are audited, but they are looked at on an annual basis as part of the return.

Q969 Dr Naysmith: On an individual company basis?

Dr Harvey: On an individual company basis.

Q970 John Austin: May I move on to the issue of the medicalisation of society, the society in which there is a pill for every purpose and a capsule for every condition? Earlier on the Chairman used the phrase disease-mongering. In evidence earlier in the inquiry, we had a suggestion from the organisation No Free Lunch that disease awareness campaigns were undermining our collective sense of well-being so that we were all instinctively reaching for the medicine chest. In their evidence, the Royal College of General Practitioners referred to the invention or creation of diseases, the categorisation of normal behaviour or conditions as abnormal requiring drug treatment. One of the examples given was mild depression, conditions where drug therapies may be either ineffective or inappropriate. We have had evidence as well which quoted an article in the BMJ which said one of the recent examples of the corporate sponsored creation of disease involves an emergent condition called female sexual dysfunction (FSD). Highly inflated and misleading statistics about the prevalence of FSD are being promoted by some drug companies and misleading information is being reported in many media stories. Do you have any fears about this popularisation or creation of disease? What are the implications, not only for drug consumption but implications for public health?

Lord Warner: Gosh, is my reaction. Certainly, if I may put it this way, as a citizen and a father, I have some concerns that sometimes we do, as a society, wish to put labels on things which are just part and parcel of the human condition which can lead in the sorts of directions I suppose that you are saying. Particularly in the area of depression we did ask the National Institute for Clinical Excellence to look into this particular area and their guideline on depression did advise non-pharmacological treatment for mild depression. What we are trying to do is strike some balance here as a society, not ignoring the pain, discomfort, concerns which people have about their health and, clearly, as employment changes, society changes, disease conditions may themselves change. It would be a surprising phenomenon if the disease conditions now were the same as they were 200 years ago, because patterns of society have changed a great deal and we just have to recognise that. A great part of the government's White Paper Choosing Health is about trying to encourage people to think more about some of the lifestyle choices they make which may adversely affect their health. There is not a lot of doubt that many of those lifestyle choices are injurious to health. There is some pretty good evidence around some of those which the Committee is well aware of. Exercise is a good example where lifestyles have changed over time, where taking exercise in the normal course of events is less common now than perhaps it was 30 or 40 years ago. These are good examples of where it does not need clever marketers to say that the social forces have actually changed the way people live their lives, sometimes with adverse consequences for their health. If you ask me whether we have an answer, I do not think the Department of Health has any more of an answer than anybody else about this very broad phenomenon other than that we try to strike a balance in many of the areas and I cited the NICE guidelines. I know doctors try to strike a balance between the pharmacological response and the non-pharmacological response.

Q971 John Austin: May I move on to an area which perhaps might be appropriate, the area of raised cholesterol levels and the possible long-term consequences of that? There is a drug available called Simvastatin, which I understand can be highly effective in advanced conditions, although - we were talking earlier about risks and benefits - there are certain potential side effects of the use of that medication, but it is now being made available in much lower dosage off prescription, over the counter and is being sold as a good preventative medicine for people with raised cholesterol levels. However, as far as I am aware, there has been no evidence, no research to show that this drug, in its lower levels, is effective in any way in preventing further coronary, arterial or heart disease. Is it really in the public interest to permit drugs, which we know are effective in certain conditions, to be sold over the counter in lower dosages when there is no clinical evidence to suggest that they are effective in any way?

Lord Warner: It might be helpful if I just talked the Committee through what actually happened in the case of that particular drug. Certainly, the safety profile of Simvastatin has been established over a period of about 15 years and the medicine has been prescribed to millions of patients. The safety profile of the very low dosage, the 10 milligram dosage, was thoroughly reviewed, not has been but was, also before the classification of the drug was changed; that was reviewed very thoroughly by the Committee on the Safety of Medicines and the pharmacy protocol for supplying the product included multiple safeguards to target its use appropriately to patients for maximum benefit and minimum risks. We did not just decide one day to change the basis for getting the 10 milligram version of Simvastatin; that followed scrutiny by the Committee on the Safety of Medicines. It went through that kind of process before it was made available over the counter.

Q972 John Austin: I think we will need to look at the other evidence that has been given to us on that.

Lord Warner: Certainly, if it would help, we can give you more detailed chapter and verse about the timings of the meetings, and the process that was gone through. We should be very happy to do that.

Q973 John Austin: I was putting it in the climate of the marketing machine which is suggesting to us that there is a pill for every condition when, as you have acknowledged, the public health agenda would suggest that there may be much more effective ways essentially of looking after our health.

Lord Warner: I certainly would not want it to be interpreted, because we had a process for Simvastatin, that I think there is a pill for every eventuality. I do think that we do have a robust process before we move drugs to an over-the-counter basis and in that particular case we can give you some reassurances and we will send you the details.

Q974 John Austin: We should like to see the published evidence because the information we were given was that there was no published evidence.

Lord Warner: Yes; fine.

Q975 Dr Taylor: This is really just a request for straight information which, if you do not have it now, we should like later. It is really about drug-induced illness. Do you have up-to-date figures for admission rates to hospital for that, the costs of that, the death rates of drug-induced illness? We are told that the figures are more readily available in some other countries and I cannot really believe that; I am sure these figures must be available.

Lord Warner: We can send you more details, but there was certainly a study by the MHRA which looked at admissions in a hospital in Merseyside in 2001-02 and it was published in the BMJ in July 2004. It showed that 6.5 per cent of admissions related to an adverse drug reaction. The median bed stay was about eight days, which accounted for about four per cent of hospital bed capacity and that, as I understand it, was broadly in line with the findings in some overseas countries.

Q976 Dr Taylor: So 6.5 per cent of admissions. Any deaths? Any figures on deaths?

Lord Warner: I do not have that information, but Dr Raine may be able to give you more.

Dr Raine: Certainly the study did look at deaths and I think it was 0.15 per cent. We shall give you full details.

Q977 Dr Taylor: And costs?

Dr Raine: The cost to the NHS projected annually would be £466 million, from that study.

Q978 Dr Taylor: Could you extrapolate that and give us a global figure?

Lord Warner: I think we would need notice of that particular question.

Q979 Dr Taylor: Could we ask you to try to get it for us?

Lord Warner: We will go away and ponder the question and try to give you the best answer we can give you, that is all I can promise. I certainly left my abacus at home.

Q980 Dr Naysmith: One of the things we were talking about earlier was the question of new drugs and their efficacy and safety and so on. This is an old chestnut with this Committee, but we are very much in favour of being able to look at old drugs as well as new ones, through NICE preferably, and we have said before that we think it is under-funded and under-resourced and if it had more money and more resources, then it could answer some of these questions much more quickly. I should just like to ask you whether there are any plans to try to encourage NICE to take on more work, which is what it amounts to basically.

Lord Warner: I am not sure that the Chairman of NICE would thank me, if I said that they should.

Q981 Dr Naysmith: I think he would

Lord Warner: I think NICE has been one of the great success stories in terms of the service that they provided to the NHS and doctors and other health professionals. We can certainly look very carefully, and we do look very carefully, at the references to NICE. I think there is a moving pattern really in which we are putting more guideline references to NICE compared with single products which is where much of their early work started. We are trying to get that better balance, so that they look at total disease conditions - it relates back to some of the earlier discussion in this Committee - they take the whole disease condition which a group of people may suffer from and look at what is the best way of treating that and put in place within their guideline, the role of the pharmaceutical product, if there is a pharmaceutical product. That is where we are trying, with the co-operation of NICE, to take many more of the references, so you get a more holistic picture of what is the best therapeutic response to particular sets of disease conditions.

Q982 Dr Naysmith: I remember when it was set up, that we were really going to look at some of the old techniques as well and it tends to get dominated by innovative drug therapies and so on, which is a pity. What you are recommending now, what NICE is doing now, will be very helpful in that respect.

Lord Warner: Fracture clinics was a good example, where you are actually looking at the phenomena which are taking place in the health service and actually balancing out the drug therapy against the whole range of services or responses that you need for people with a particular condition. There has been a very positive response from the NHS at getting that kind of guidance rather that just guidance about a particular pharmaceutical product.

Q983 John Austin: Going back to something you said earlier on when we were talking about mild depression when you made a comment that NICE now recommends against initial drug treatment use in the case of mild depression, I know that follows on as well the expert working group's conclusions that SSRIs were not effective in the treatment of mild depression. Although I welcome those conclusions, both of the expert working group and NICE and the guidance that NICE has given out, why has the MHRA not advised prescribers of patients of this?

Lord Warner: I am sorry, I am slightly confused there. The basis of NICE guidance is that that then becomes the source of authoritative advice to doctors. One would not expect the MHRA to be communicating that. I am not sure I fully understand the question.

Q984 John Austin: The MHRA's key conclusion still remains that SSRIs are effective medicines in the treatment of depression. There is no added qualification now that this does not apply in cases of mild depression.

Lord Warner: My recollection is that guidance went out at the same time, but I do not know. Dr Raine, would you like to say something?

Dr Raine: Yes; certainly. The focus of the MHRA work was to review in the context of the safety concerns, risk and benefit, but the therapeutic advice, which was issued at the same time, was very much for NICE's remit. The two are not consistent, they should be read together.

Q985 John Austin: You do not feel the necessity, although you have the opportunity now, to modify your key conclusion.

Dr Raine: No, I do not think it needs modifying. It is to be taken in conjunction: the regulatory risk benefit advice and the NICE guidance on the therapeutic options.

Q986 John Austin: One of the other issues I want to raise is the implication of licensing of drugs for particular purposes. The license use of SSRIs for mild depression led, I am told, to a three-fold increase in prescriptions in the 1990s. Do you have any comments on that?

Lord Warner: I do not have any particular insights to make on that particular surge in the use of that particular product. It is not unusual for new products, particularly when they are thought by doctors to be useful for their patients, to have a big surge in take-up. One has seen that in the area of attention deficit drugs as well. What I would say is that we have tried to balance that with the kind of guidance that we have given through the NICE process. As I said earlier, the Audit Commission study that I mentioned of wasteful expenditure showed a marked decline in the period between the early 1990s and 2003 in terms of prescribing habits, so we ended up at two per cent rather than 13 per cent. That Audit Commission study suggests that prescribers are being more cautious than they were in the past about leaping on band wagons and engaging in wasteful prescribing.

Q987 John Austin: May I come on specifically to the findings on Seroxat and the expert working group? The working group learned of the seven cases of suicide in the original clinical trials, but they appear to have accepted the company's assurance that none of those cases was linked to adverse drug effects. We now know that GlaxoSmithKline, or SmithKlineBeecham as it then was were aware of the potentially serious consequences of withdrawal symptoms much earlier on, even though they were still maintaining that such cases were rare, which we now know was a fraudulent statement. The MHRA and the expert working group do not appear to have ever examined the raw data; they merely seem to have relied on the information given by the pharmaceutical companies.

Lord Warner: We went over the ground earlier about the general points about raw data; I can go over that again. On the specific issue about whether that particular company did withhold information - and in a sense it does not matter whether it was raw data or a summary of the clinical trials, the same arguments apply to what I am going to say - if they did in fact withhold information, that would be an illegal act under the medicines legislation and the MHRA, through their enforcement arm, are actually investigating the allegations that have been made in that particular case. That investigation is not complete. I cannot at this time, as you will understand, make any further comment on it other than to say if it is found that there is evidence of non-conformity with the medicines legislation in providing the information that is required to be provided, you can take my assurance that there will be vigorous prosecution in that particular case, if that is the case.

Q988 John Austin: I am grateful for that. I was somewhat concerned that someone who could have been a key witness mysteriously could not turn up and give evidence to us when we wanted to ask certain questions at a previous session. My question still remains. There was a detailed 18-month inquiry. If the MHRA does not examine the raw data on suicide cases in a detailed 18-month inquiry, are we to conclude that the MHRA rarely does so?

Dr Raine: Perhaps it would be useful to stress again that in relation to paroxetine we went back and re-examined the original trials. In that case, the rigour has extended to that level of detail. If it would help the Committee, I should be very happy to produce a short note on the precise methodology which was employed just to clarify that point.

Q989 Chairman: It would be helpful.

Dr Raine: The published document we now have is some 200 pages long, so a concise note may be helpful.

Q990 John Austin: Were you looking specifically at anti-depressant safety?

Dr Raine: Selective serotonin reuptake inhibitor safety; that is correct.

Q991 John Austin: You were not looking at the wider issues of risk and benefit in that area.

Dr Raine: Certainly the focus was on the safety concerns. This was the prime reason for the rigorous review. It had to be taken in the context of this very serious illness which is a major burden to the public health. The report itself makes that very clear in one of its first chapters.

Q992 John Austin: May I say that at the last session the Chairman of the MHRA, Sir Alasdair Breckenridge, referred to the importance of not discussing the question of drug safety in isolation and emphasised the need for education of the public in terms of risk and benefit. I presume that is something you would agree with.

Lord Warner: Absolutely. I was very much trying to get that point across in the earlier evidence I was giving. On the issue of raw data, my understanding is that in the inquiry on which you have been pressing us, two products, Epogam and paroxetine were actually subject to very significant partial re-analysis of data. There was a going back into the raw data in order to look at some of the issues around suicides and suicidal indications. In that particular case, the MHRA did not spend the length of time on just one product, it was a large range of products; where there was the need they went back into the raw data to do a re-analysis. It simply is not true that under no circumstances do they use the raw data: in most cases it is not necessary to do so.

Q993 Dr Naysmith: It has been suggested in evidence to us that the post-marketing surveillance function, checking particularly that licensed drugs are safe, should be removed from the MHRA just to avoid possible conflicts of interests arising. What do you think of that?

Lord Warner: My sense is that this does not happen in other drug regulatory bodies. While I make a few more remarks, I give my two colleagues time to consider whether they can think of any other country where that division has been made. I do not think there has been, from recollection.

Q994 Dr Naysmith: Can you understand how, from the outside, it looks as though there must be some conflict of interests when the minister responsible for drug regulation is also the co-chair of the pharmaceutical industry competitiveness task force?

Lord Warner: There are two things, are there not? There is the situation within the regulator and the situation at the political level with the minister. Within the regulator, there is operational separation of post-licensing supervision in the form of Dr Raine and the people who are dealing with the original licensing applications. It is useful to have within the overall body both these functions combined, although there is a clear separation of the staff who are working on those two particular functions and it only comes together in the chief executive across the agency. It becomes easier for the post-licensing scrutiny of a particular product to be carried out if they can get access easily to the data which was around at the time of the licensing application itself; that becomes operationally a simpler thing. I would argue there that there is not much of a case for separating them up into two bodies with all the overheads which go with two bodies when there is no evidence, as I recall, that any other country has gone down that path.

Q995 Dr Naysmith: I think the Netherlands have, have they not?

Lord Warner: There is some doubt as to precisely what they have done.

Dr Harvey: I think in the Netherlands the final decision around pharmaco-vigilance still sits with the licensing body.

Dr Raine: Yes; absolutely. Although they collect ADR reports and do a certain amount of signal detecting work in a separate body, it is the licensing body equivalent which does the risk assessment and risk management decision making.

Q996 Dr Naysmith: They definitely separate pre- and post-marketing functions in the Netherlands.

Dr Raine: It is not directly comparable in that way. There is a separate collecting of ADRs but not the decision-making process, which is centrally done.

Lord Warner: So the actual decision to withdraw is taken by the same people who take the decision to licence in the first place. I think that is the point my colleagues are making. In terms of your other point about whether the person sitting in my job, past, present or future, is able to strike the right balance, I tried to get the arguments across in my opening responses to the Chairman's questions. I think a balance can be struck and I think it is important that we do not get into a situation - the only point I would emphasise - where preoccupations with short-term financial issues in relation to healthcare, which is a problem in many countries and certainly is a phenomenon in some European countries at the moment, actually dominate the decision-making in relation to the future development of particular products. If there is no scope for encouraging the development of research-based products in this area, the only people to suffer ultimately are the citizens of that country because you diminish the flow of new pharmaceutical products onto the market through a research-based industry. We think that balance has to be struck and under successive governments we have struck that balance by combining in one department the responsibility for running the NHS effectively and being the sponsor organisation for the research-based pharmaceutical industry.

Q997 Chairman: What I think Doug is after, and it is an interesting question, is whether you find, as co-chair of the competitive task force, also with responsibilities for the regulatory mechanism, that on occasions you have to make some pretty difficult decisions on which side of the fence you may need to go. You have an industry which is hugely important to the economy, employs thousands of people and is a major earner for Britain, but on the other hand you have that very important responsibility in terms of public health. Have there not been situations where you have found yourself in some difficulty in determining exactly whose side you are on at a particular time? Issues must have cropped up which have caused you some problems in that respect.

Lord Warner: I certainly do not want to give the impression that I am cavalier about this. I do think about these issues very carefully and I certainly do not want to give the impression that I am schizophrenic either. What I think I would say is that if you are trying to achieve a balance and that is what you are consciously trying to do, you work hard to achieve that balance. I try to ensure that I hear what the industry has to say, I sometimes, if I am honest about it, take what they say with a pinch of salt and I particularly sometimes take it with a pinch of salt during the course of PPRS negotiations. I would point to the PPRS negotiations as a good example of where this balance can be struck. We certainly did not end up in those negotiations where the industry wanted us to end up and there was much rhetoric from the industry, if I may remind the Committee, about a settlement being forced upon them. There were not loud hosannas in some parts of the industry about the outcome of those negotiations. Equally, however, at the end of the day, the ABPI recommended that settlement to their industry. There are difficult judgments and there is hard bargaining to be done sometimes in some of these areas. We have touched on some of these issues around enforcement, when there is poor practice, if you like, in relation to supplying evidence. Where there is evidence that people have not supplied the information that they will be required to under the medicines legislation we will not hesitate to take tough enforcement action. I believe that it is possible to strike that balance, but I can see other people might find that the arguments go the other way.

Q998 Chairman: Cross-dressing in politics is apparently quite fashionable, but you seem to be in an impossible cross-dressing position in the role you have. What I am interested in are your thoughts. What would be the impact if the commercial aspects, the competitive task force aspects of your role were actually within DTI and the regulatory remained within Health? Can you see any advantages or can you see any disadvantages? Obviously that is an issue which, as you appreciate, has been thrown around throughout our inquiry.

Lord Warner: Once you separate those two functions it would be far more difficult to get the right balance. You set up a scope for conflict departmentally within government if you go down that path and I would still cite Europe in that particular case. Where the going gets rough in public expenditure terms and you have a slightly embattled health minister trying to cope with a burgeoning budget against the wishes of some of his colleagues, this does not of course happen in this particular country, but overseas there are sometimes less favourable circumstances that this government has managed to achieve in this area. Where you get that, there is always the danger that the short-term consideration, in terms of balancing the health budget, will over-predominate. That is the argument I would ask you to dwell on. I would say that can be detrimental to the longer-term interests of the citizens of that country in terms of the health products which get developed. There are countries in Europe which did, 10, 12, 15 years ago, have strong pharmaceutical industries which have actually weakened very substantially over the last 10 to 15 years.

Q999 Chairman: What you are saying is that this cross-dressing I referred to is not an impossible task from your point of view.

Lord Warner: I do not want to come across as a fervent cross-dresser and I never quite see myself in those terms, but if that is the label the Committee wish to apply to me, I am comfortable in that position.

Q1000 Dr Naysmith: There is a slightly different angle to all this, which is that this must mean there is a fairly close relationship between the Department of Health and the pharmaceutical industry. It is possible that means that solutions to health problems are sought more quickly and more readily, from pills and that sort of thing, than other potential treatments which the department also ought to be considering and perhaps promulgating more. It is even more important when you are talking about budgets, because quite often it is cheaper to prescribe pills than it is to prescribe a course with psychologists or psychiatrists or physiotherapists. It kind of skews the thinking about health and public health away from a longer term solution to a lot of problems. What I am asking is whether there is any possibility that could be happening.

Lord Warner: The other argument is: who is doing what? The person in the department who is the lead official on relationships with the pharmaceutical industry is Dr Harvey. She is balanced in terms of all the sources of advice to ministers that feed into public policy decision making by a raft of other people who are arguing the cases for public health, particular disease conditions, mental health, acute services and so forth. At the pinnacle of this is the Secretary of State making judgments based on a variety of sources of influence. There is no one person saying that at all costs we actually have to have a pharmacological solution to this particular health problem. I should say the arguments increasingly are the other way round, where people are being encouraged to take more responsibility for their own health. There is a strong drive in that particular area, giving people more information about their own health conditions, encouraging them to find out what are the best ways of responding to those conditions, a lot more emphasis on choosing lifestyle options which favour health rather than those which do not. That is a set of very strong messages going on in the public arena and the advice which is given to ministers, which is a counter-balance to any suggestion that we might just want to promote pharmaceutical products.

Q1001 Dr Taylor: May I go back very briefly to the cost of adverse drug reactions? I realised rather belatedly that I did not make my question quite specific enough. You told us that about 6.5 per cent of admissions to hospital cost £466 million a year. Does that include the cost of treatment in hospital? Is that a total cost for that?

Lord Warner: I would have to bow to Dr Raine.

Dr Raine: It was a total cost, but we can certainly give you a note on the specifics.

Q1002 Dr Taylor: The other thing which is probably not recognised is the cost of adverse drug reactions in the community. Is there any measure of that? The loss of work which a drug reaction causes for a patient who never goes near hospital. I have only just realised by the mirth which was engendered by my use of the term "global" that you were thinking about the whole world. I was thinking about the global cost in this country, the community and hospital services. Is there any way you could find out about that?

Lord Warner: We will certainly look into it. My impression from the study I cited was that it related to the people who were in that particular hospital, but we need to look at the evidence.

Q1003 Dr Taylor: Hospital admissions are easy to collect; it is what is happening in the community which is more difficult.

Lord Warner: We also have the GP research database. We will genuinely look into the data we have and give you the best estimates we have on that basis. I am afraid I cannot answer in any more detail today.

Q1004 Dr Taylor: Moving on to innovation, we have heard from several witnesses that really the rate of new drug discovery is going down and this is almost inevitable because it obviously becomes more and more difficult to find new answers. A question which has been put to us: would a stricter regulatory system encourage more real innovation? If one had got to 12 beta-blockers and you said enough was enough, 25 non-steroidals and you said enough was enough, would that in any way encourage drug firms, force them to go for real innovations? One would cut the beta-blockers and the non-steroidals well before you got to 12 or whatever the numbers were.

Lord Warner: The whole area of innovation is a complex one. It is wider than just stopping particular pharmaceutical products. I have been involved in that in other aspects of my work as well as the work on the pharmaceutical industry. Certainly you have a pharmaceutical industry which has a very big R&D component; there is no doubt about that. They spend £3.5 billion a year on medical R&D. We have an NHS which is putting in over £600 million to R&D and we have the Medical Research Council and the charitable sector. There is a very big component of medical clinical R&D in this country which is driving an agenda of change in this particular area. What we have found, which is why we set up last year, after a couple of reviews, one by Sir David Cooksey and one chaired by Sir John Pattison, was that there were real issues about how fast we were getting innovation to the bedside from the laboratory. So there were issues around whether we could do a better job on what is called translational research in terms of getting clinical trials off the ground. It is worth bearing in mind that the evidence shows that patients who are in clinical trials tend to do rather well compared with people who are not in clinical trials. Whatever the outcome of the trial, there are benefits for patients. We found that area is one which needs a great deal of attention and that is not just in order to benefit the pharmaceutical industry, it is actually to bring good products faster to the bedside for a whole range of people. We also think, as I was saying earlier, why we want to move down the path of a futures forum is in some ways similar to the points that Mr Bradley was making about the World Health Organisation having a medicines policy. We think we need to be a bit more holistically looking ahead about the things we should be concentrating R&D effort on a bit more than we have done in the past, which is why we want this futures forum. We do know that generally in the NHS you need to use - this is not just about pharmaceuticals but things like devices as well - the purchasing muscle of the NHS to bring some of this innovation faster to the advantage of patients. This is a complex issue where it is not just a straightforward matter of stopping one line of development for a particular range of pharmaceutical products: it is a complex issue about how you foster innovation, the development of new therapies and bringing the new therapies to the patient quickly through a proper trial basis.

Q1005 Dr Taylor: Are there any incentives which could be offered? It is obviously incredibly expensive to develop a completely new treatment for something and it is presumably far cheaper just to develop a minor variant of the drug. Are there any incentives which could be offered to encourage the real innovation?

Lord Warner: It is not quite true that some of the me-too drugs have not themselves been of great benefit to patients. It is not always the case that the first-in-class product has been the one which has been the winner for patients, as you probably know from your own clinical practice. We could certainly send you some evidence. The point I am making is that there comes a point about when you stop me-too and next-in-class in a particular class of drugs. Those would not be easy judgments to make.

Q1006 Dr Taylor: One of our witnesses felt that three beta-blockers would probably have been enough. I wondered whether there was any way the regulatory system could provide an audit and quality control of these sorts of developments and that would therefore produce some regulation of them and a push towards major innovation.

Lord Warner: Thinking about this, particularly in the light of what Mr Bradley was saying earlier, it seems to me that this is the kind of area you would touch on in a WHO recommended medicines policy. You would start to take a picture of where the areas of less involvement were and where the areas of excess involvement were. It seems to me to fit more easily into that kind of work rather than using the regulatory system to try to block entry, if I understand you correctly.

Q1007 Dr Taylor: Yes. I was just wondering how possible it would be for the MHRA, when there were six beta-blockers all with slight differences, to say to a firm which was going to produce a seventh that we do not need it.

Lord Warner: I do not have anything more to add. The firm would still have to show safety and efficacy in their product to the MHRA, if they had a new product in that particular area.

Q1008 Dr Taylor: Back to a point which has continually been made to us, all that has to be shown is that a drug is better than a placebo, not better than a standard. That seems to me to be a weakness in the system.

Lord Warner: I am not the scientist here.

Dr Raine: It does depend on the therapeutic area; there are different approaches depending on whether comparators are looked at or indeed placebos. We could perhaps give you a short note on how the regulatory system works in that regard.

Dr Harvey: The minister referred to the futures forum and the UK CRC, the UK CRC involves all of the major funders and indeed patient groups and the pharmaceutical and medical devices industry and is a way of stimulating research across the board and a way of building on the original cancer networks we have had in the NHS to build networks around mental health, children, stroke, Alzheimer's, etcetera, where one is actually engaging with the major research bodies and the pharmaceutical industry, devices and patients in the sorts of areas which are clinical priorities where actually we need the development of new agents. As the minister was saying to the futures forum, engaging with the pharmaceutical and indeed the devices industry with these major funders and patients does make it clearer to the industry where the real areas of priority need are for the NHS.

Q1009 Dr Naysmith: On that, I was speaking earlier about the PPR scheme and the possibility that there was an allowance for marketing it. There is also a big allowance in it for research. Is that ever used as any kind of driver in this area or could it be?

Dr Harvey: In terms of the 2005 PPRS, you are absolutely correct that in terms of the allowances, the allowance for research and development was increased within this particular agreement and that is particularly to stimulate innovation with development of new active substances.

Q1010 Dr Naysmith: Were the companies who had innovated rewarded or will they be rewarded or is this something that everybody gets?

Dr Harvey: No; no. There is a baseline research and development allowance, but then there is an allowance specifically targeted at the number of new active substances a company has which are in patent. A small company gets slightly larger allowances; very large companies get a fixed allowance for up to 20 new active substances. This is building on what was there within the 1999 scheme, but is very much there around stimulating innovation.

Q1011 Dr Naysmith: What about quality. Does someone check what has been innovated and say whether it is a good thing?

Dr Harvey: It is around the development of new active substances, so they have to be new chemical entities.

Q1012 Dr Naysmith: New in terms of fulfilling a need or another version of an existing product. Who will decide that?

Dr Harvey: Technically it could be another version, but it has to be a new active substance in its own right. In addition to that there is also an allowance of up to three per cent for the development of paediatric licence to medicines as well. That is new within this PPRS agreement and is very much in line with the minister's commitment around having more licensed treatments available for children for paediatric use.

Q1013 Dr Naysmith: The minister said early on - I wrote it down - that one of the aims would be to get the science applied faster where there is a clear patient need; or it may have been a clear clinical need, but the rest of it is accurate. That is what we should be trying to do, is it not? If we can do it through that mechanism, then we ought to be looking at it.

Lord Warner: There are various ways. Paediatric medicine is a good example of where one is trying to get the incentives all pointing in the correct direction. If we are frank about it, this has been a rather neglected area in the past, which is why we will be publishing a British national formulary for paediatric medicine later this year - the work is being done by all the experts in this field - and why we want to give incentives through the PPRS and negotiations are going on in Europe over this particular area. Everyone recognises that one wants to use the mechanisms available to try to get the incentives where there is clear public benefit and paediatric medicine is a good example. It is also worth mentioning that the Chancellor has made available a tax credit for research and development which the pharmaceutical industry would benefit from, as would the biotech industries.

Dr Naysmith: We have had evidence in this Committee that quite a lot of patient groups receive funding and support from drug companies. I wonder whether you think it is worth enquiring into such relationships and possibly even considering legislation to control these groups because they could be acting as unwitting foot soldiers for the pharmaceutical industry.

Q1014 Chairman: One of the things we found interesting was the number of all-party groups within parliament who also have interesting connections, often not known to their members, with industry.

Lord Warner: This is a difficult issue. I should just declare to the Committee that before I became a minister I was the chairman of the National Council for Voluntary Organisations, so I do feel slightly schizophrenic on this particular issue. This particular issue is not peculiar just to the taking of money from pharmaceutical industries for voluntary organisations. All voluntary organisations are confronted from time to time with whether they want to take a particular sum of money or types of funding from a particular source when it may, as they see it, produce a conflict of interests or compromise their own independence of judgment. It is ultimately in this area down to the particular voluntary organisation to consider very carefully whether they are damaging their own reputations by taking money from a source which may call in question the arguments they put forward on behalf of a particular patient group or particular interest. It is not peculiar to the area of taking money from the pharmaceutical industry.

Q1015 Dr Naysmith: Should some sort of statement of interest be required, along those lines?

Lord Warner: Absolutely. They do all have clearly defined charitable purposes in order to be registered as a charity and the funding should not be in conflict with their charitable purpose, whatever that is. They do have to make sure that it is consistent with the benefit to their beneficiaries. Certainly the Charity Commission offers a range of guidance to voluntary organisations. I am certainly happy to look into whether this issue has been raised with them, whether there are particular areas. I do not know whether the Committee has actually taken that in.

Q1016 Dr Naysmith: We have the Charities Bill coming soon which may well be an appropriate route.

Lord Warner: Absolutely. Certainly, if there is an issue, I think it is to a great extent dealt with through the charities route.

Q1017 Dr Taylor: You mentioned the withdrawal of Coproxamol, which is really quite a milestone, because I suspect it is the first time that a drug which has been around for so long has been withdrawn. I can see some of us being approached in our constituencies at home by long-term rheumatoid arthritis patients who can see no way that they are going to get off it. May I just ask what consultation there was, what bodies were consulted about the withdrawal? Everybody recognises that even in small overdose it is dangerous, particularly with alcohol, but what consultation was there before this absolutely drastic step of getting rid of it altogether was taken, when perhaps it could have been available under some scheme of limited prescribing?

Dr Raine: Recognising the concerns which Dr Taylor has expressed about a very well-established medicine, albeit one without evidence of a favourable risk benefit, that the withdrawal would pose very major issues for clinical practice and for patients, for the first time we conducted a public consultation. We put the evidence base into the public domain and sought comment about the very question you are asking: are there specific groups of patients for whom the benefit risk would be favourable. We ask not just for evidence, but for arguments and opinions. The results of that consultation are published. In the end the CSM had to weigh all this up in light of the scientific evidence and make a very tough decision. What I would say is that we can also convene a pain management working group under the leadership of the CSM in order to help that change in practice. Quite clearly, if there is a very small number of patients who do indeed need ongoing supplies, we could consider a named-patient-basis type of arrangement. I hope this gives you the perspective on the lengths to which we went to gauge public opinion in this regard.

Chairman: May I thank you, minister and your colleagues, for an excellent session. You promised to come back to us with some more information and we should be grateful for it as soon as you reasonably can do it, because we have to produce this report before too long. Thank you very much for your help.