Select Committee on Health Minutes of Evidence


Examination of Witnesses (Questions 700 - 719)

THURSDAY 13 JANUARY 2005

MR EDDIE GRAY, DR STUART DOLLOW, MR CHRIS BRINSMEAD AND DR JOHN PATTERSON

  Q700  Mr Jones: Moving on, most countries, in fact almost all countries, do not allow direct-to-consumer promotion of prescription medicines, although notably the United States does, and your pharmaceutical companies are enthusiastic participants in that in the United States, which is what you have to be really within that system. Do you think that direct-to-consumer advertising has much to recommend it to other countries?

  Mr Brinsmead: I think my position would be that we in this country are happy with the situation and would not be pushing for direct-to-consumer advertising on behalf of AstraZeneca anyway at this moment. I think what we would think is important is that the provision of medical information about a product to patients should be possible, so I think we have to distinguish between advertising on television and in magazines, that type of activity from providing information. The fact is that if a patient wants to know about a drug or a disease, they can go on to a website and they can use the search engine and they will get lots and lots of information. It could come from anywhere and the information may or may not be validated. I think it is important that there should be some way whereby pharmaceutical companies, who by definition have most of the information, especially if it is a new product they have been researching, can make sure that information is available to the patients, to doctors and to the people who want to know about that.

  Q701  Mr Jones: Mr Gray, since your company operates in the United States and in this country and other European countries, you would be in a good position to compare and contrast the values.

  Mr Gray: Yes. In addition, I was personally living and working in the United States in the early `90s when the DTCA all started. I think I learned from that that any form of communication has to sit comfortably in the cultural context. It was very interesting. The friends my wife and I had when we lived there were the people who lived around us and parents of children in the schools, so they were not industry people. Some of them were doctors in the system. I have to say that those people, pretty overwhelmingly, thought DTCA was a good thing. They felt it was consistent with "American life" for want of a better phrase. They wanted the information; they were very, kind of, proactive about which doctor to go and visit and all of that kind of thing. I think my sense of the UK is that the cultural context is not appropriate for direct-to-consumer advertising. I do not think the public want it and as an organisation we are not pressing for it.

  Q702  Mr Jones: Do you see, in this country, sponsorship of selected patient organisations and disease awareness campaigns as a substitute for direct-to-consumer advertising?

  Mr Gray: I do not see it as a substitute at all. I see disease awareness as a separate and valid activity. I was talking earlier about the issue of: Do we invent diseases and are we trying to stretch the criteria? and I think another part of the element that has got mixed up in that is this issue of whether there are also patients, kind of, being forced or encouraged into the system who should not be. If you look at the current attitude of the National Health Service and how at the moment, particularly in primary care, with its focus and attention on long-term medical conditions, the National Health Service is actively looking and seeking to get patients in as early as possible and that is to the benefit of the patients. If you look at the current new general practitioner contract, for example, various measures which lead to GP payment are around issues like: Do we know if all these patients are in a particular condition? Do we have a register of them? Are we seeing them ever so frequently . . . on a certain frequency? et cetera—nothing to do with whether or not there is any treatment involved. Those are important measures for the ongoing health of these long-term conditions. The other thing—which sometimes is a bit galling, quite honestly—is that often the best balance of management of a patient only really comes about if you can make the patient aware and get them to access the system early. If I think about diabetes, for example, everybody would say for Type 2 diabetes that the first thing you do is a regime of diet and exercise. Everybody says that, including us: it is on all our materials. But of course the later a person actually is caught and presented for Type 2 diabetes, the less successful diet and exercise is and the accusation is: Why are they on drugs so quickly? Well, actually, because they turned up too late. The earlier they turn up, then the more successful that period of diet and exercise and the more elongated that can be. We do take part in such activities. I have one here: there is no promotion involved in it at all, and we do have examples of people who have responded with words of thanks on the basis of: "I read that and realised some of those applied to me and I have gone and done something about it"—interestingly, including a member of parliament. So it forms a valuable service, and I see it in isolation and not as a substitute for anything, quite frankly.

  Dr Dollow: If I could supplement that and reflect on my experience. I used to be a hospital doctor and a general practitioner, and, when you see patients coming in who are informed, it enables you to have a debate with them about their health. So many of the things in medicine are not black and white, they are about making choices, and if patients are informed about how to help make those choices they are engaged with the management of their own disease. That has to be a benefit. If, however, a patient comes in and you find they simply do not have the disease, you can say, "Well, it's good that you are aware of it, but you don't have it so I don't need to worry about it." I think that individual doctor/patient relationship has to be seen as the final and appropriate gatekeeper of the information that gets to patients through disease awareness.

  Q703  Mr Burns: Could I pick you up on that point because there is also a counterview to that, which is that there is a growing problem in the patient/GP relationship because individuals are going into the GP practice, having read some information from a variety of sources, including the internet, and telling the doctor what is wrong with them. Then, when the doctor examines them and does not agree, a blazing row ensues because the patient believes that the doctor has got it wrong. On the argument that a little education is worse than no education at all, a lot of GPs are having serious problems with their relationships with their patients.

  Dr Dollow: All I can do is reflect on my experience and the experience of friends and colleagues.

  Q704  Mr Burns: With respect, how long ago was that experience?

  Dr Dollow: My experience was 14 years ago, but . . .

  Q705  Mr Burns: That was before the internet.

  Dr Dollow: But friends and colleagues who are currently in general practice I still talk to and I think I can reflect on the discussions that they have had with me. There are occasionally disagreements, but, in most cases, some patients have been sent away, saying, "No, you haven't got that," and with some patients saying, "Yes, actually you have got that and it is worth you doing something about it," which may or may not require a medicine.

  Q706  Chairman: As you have indicated that you have looked at videos of previous sessions, may I raise the evidence given to us by the Royal College of General Practitioners' witness. You may remember, a practising GP spoke in some detail about her concerns over the way in which, as a consequence of the industry's marketing and, in her view, disease mongering, she was faced with patients, particularly on the osteoporosis issue, coming in with all sorts of concerns that she felt really were completely wrong. She was very strong in saying that we are into a climate now where people come in having had their minds made up about their own health problems, and it creates immense difficulties for people like her. Did you see that?

  Mr Gray: I did. I think there is a very pertinent kind of connection with the previous question. Nowadays, I believe I am right in saying, health on the internet is the biggest content behind pornography. From our point of view, in terms of any disease awareness activity in which we have been involved I am extremely confident that we apply to it exactly the same standards that we apply to everything else. I think, if you have looked at any of the health information available on the web, there is a range from very respectable right down to complete and utter cranks. Ours, as a percentage of the total that is available, is actually really very small. So I do believe you are probably right that many General Practitioners, as Dr Heath, I think it was, confirmed in her own evidence, are experiencing this problem, but the idea that it is a function of what we are doing . . . I think the world has well moved beyond that. The sheer amount of information on the internet now on health matters, completely unregulated, I suspect, is much more a contributor to that situation than anything in which we are involved.

  Q707  Dr Taylor: Turning to research and innovation, we have all seen a huge explosion of really important new drugs over the last 40 years. There is a list as long as your arm. The discovery of those sorts of huge innovations really seems to have slowed down. Is this inevitable? What fields are you looking at? We have had a very useful paper from the ABPI about polio, river blindness, trachoma, HIV, tuberculosis—all the things in the less well-off countries. What sort of areas are you looking at to increase the rate of innovation?

  Dr Patterson: We look across, we think, about 80% of medicine in the therapeutic areas in which we research, so most of the areas that you would regard as key priorities or the major causes of morbidity and mortality, but no one company looks at all fields, for instance. Could I pick up on that innovation has decreased. We have seen, in the last few years certainly, a reduction in the number of medicines getting to the market place, but I think amongst them are some very significant and very innovative medicines. People fail to understand just the length of time and the investment required to get them there. Perhaps the best example I can give you is monoclonal antibodies. They were discovered in Cambridge in the UK in 1976 but the first medicines based on monoclonal antibodies only got to the market place in 2000 and it is only now that we have, sort of, 10 or 12 of them out there and actually it is only now that the first fully human monoclonals—because the early ones were antigenic and could not be given multiple times—are beginning to come through. So that is something like 30 years from their discovery. During the 1990s a lot of the human genome work was undertaken. Many exciting new things came out of that and somehow the world expects instant gratification. I suspect, if I am still working in this industry in 2015 and 2020 that gratification will start to hit the market place, but if you add 10 years from when a medicine is first discovered to get into the market place, to the science that is required to turn a SNIP or a change into our understanding of the genome into something that has become a medicine, you are talking 20- to 30-year time periods. During the '90s, in addition to all the classic organic chemistry, small molecule type work that industry was doing, we had to add in all the new science. We have finite resources too. Most companies diverted resources into those things and as a result there was a slowing down of some of the other small molecule work. I hope we are going to see in the second half of this decade the fruits of some of those labours beginning to speed up again and most of us would say our early development portfolios, those products that are in pre-clinical or phase 1 and 2, are now significantly greater than they were five years ago.

  Dr Taylor: Thank you. That is very clear.

  Q708  Dr Naysmith: I am going to move on to a subject which has been described to us as "pharmacovigilance" although I am not sure what that term really means. Would it be fair to say that, once drugs get licensed and are on the market, companies typically spend a lot more time and money on demonstrating their benefits than investigating and looking at their potential harmful effects? Do you think that is true? If it is true, do you think they have the balance right?

  Dr Patterson: I think that is an outrageous statement and it is not true at all.

  Q709  Dr Naysmith: Not true at all.

  Dr Patterson: I think we have a legal, moral and ethical duty to follow the safety of our products from the moment they go to the first patient through to the moment we stop producing them or they stop being on the market place. Our adverse reactions programmes and processes are global. We have large numbers of people employed in our organisations whose sole role in life is to collect, collate, examine and analyse those activities. We have a thing in AstraZeneca called the SERM process (the safety, evaluation, review mechanism). It is a community of people who have nothing to do with the efficacy of our products or nothing to do with the marketing of our products. They are doctors and scientists and epidemiologists whose job is to review the data on a regular basis to make sure there are no signals coming out, there are no adverse reactions coming out, and then to make sure that if we see those things they are dealt with appropriately, either by, at the very extreme, stopping selling the medicine, or changing the data sheet or informing health authorities. In addition to that, we have regular safety update reports that we make to the health authorities, and, again, depending on the severity of the adverse event, we report either rapidly or on a periodic basis. When a product is newly in the market place, we often have more onerous needs than before. It is all there. We also monitor not just everything that comes into us spontaneously but the world literature for anything that is reported there, and we take every regulatory authority worldwide database and feed it into ours so that we can get the most comprehensive worldwide database of safety. Then, as soon as we have a signal or an issue, we talk to the health authorities, we vary our licence or we take the appropriate steps.

  Q710  Dr Naysmith: That is all very commendable. Have you ever suggested to the Government ,in this country, or the Department of Health,that the system they use in this country for reporting adverse effects of drugs does not really work? I am sure Dr Dollow will confirm that the card system, where a card is supposed to be sent in by GPs and hospital doctors when they see adverse effects, is widely recognised to be a bit of a nonsense. Dr Patterson, you would find a lot more adverse reactions being reported to you if we had a proper system for doing that.

  Dr Patterson: The UK, of course, represents only about 3% of the sales of our products globally, so it is a relatively small percentage.

  Q711  Dr Naysmith: It would be a statistically significant cohort if you were studying something about a drug.

  Dr Patterson: That is certainly true. We would always encourage every country to have the right kind of systems that are as comprehensive as possible. Of course we do have in the UK the Southampton unit which actually prospectively goes out and takes cohorts of patients and looks for specific events. It is not instead of spontaneous reporting but in addition to it, to get these things put into the context of the wider usage. These things are not absolute: you have to put them into the context of the disease and the other medicines that are available.

  Q712  Dr Naysmith: Does Dr Dollow agree with me that the card system, on which medics are supposed to send in adverse effects, does not work very well?

  Dr Dollow: Let me reinforce, first, John Patterson's view. GSK has a system which is essentially similar, in that we absolutely report all adverse effects on a global basis to all authorities worldwide but we can only work with the information that we glean from our clinical trials and spontaneous reports and systems such as yellow cards. We again have a large safety department in the UK and the US and around the world which reports these adverse events. They are individuals who spend much of their day trying to get much more information. I think the yellow card system was a great innovation. I think the difficulty, as people have previously said, is its expansion: whilst supported—and we would certainly recommend that any expansion of it be supported, including patient reporting—the difficulty behind it is getting the robust information. In one of the previous evidence sessions, Professor Vallence mentioned the use of the general practice research database. That is a very good idea and we would certainly recommend that GPRD is expanded to beyond the cohort of patients that it currently has. Currently GPRD works by a diagnosis being put in and the name of a medicine being put in and then the analysis has to be associated by someone specifically doing an analysis. We would recommend not only expanding it as part of National Health Service IT expansion but also people putting in adverse events and labelling them as adverse events so they can go further in. So I think the yellow card system is very good and we support its expansion but I think there is more we can do. Certainly we would be very welcoming of anything the Committee recommend to support that.

  Q713  Dr Naysmith: We are getting a bit short of time now, but could I quickly ask GSK about Seroxat and the fact that, up until quite recently, June 2003, the company maintained that withdrawal symptoms from Seroxat were very rare, round about 0.1% was the figure, and now you have to accept that it is nearly 25%. How did that come about? There is evidence that you knew before June 2003 that the figure you were using was wrong.

  Dr Dollow: I think it is important to put it in context. I think it is a good example of how labels change over time: so the labelling, be it in the patient information or the doctor information. I would confirm also that withdrawal effects and discontinuation symptoms have always been in the Seroxat label, so it has always been there both in the patient side and in the doctor side. It has, however, been updated over time as more information has become available to us. The fact that more information becomes available to us allows us to make a reasonable recommendation based on the data, so that we can say the frequency of those adverse events and the descriptions used for those adverse events is more appropriately labelled. Additionally, I think, when it comes to patient information leaflets, it is a very good example of how patient information leaflets can be worded more appropriately. Seroxat is an example where we have extensively done user testing. Patient information leaflets, while they legally have to be compatible with a summary of product characteristics, sometimes are written in a way which is unhelpful to patients. We have found through the Seroxat process and through extensive user testing that the patient information leaflet is now more friendly. I think we would also recommend that more user testing happen with patients, such that they are written from a blank sheet of paper whilst still being compliant with the summary of product characteristics.

  Q714  Dr Naysmith: Despite what all of you have said, does this episode not indicate looking a bit more closely at some of the harmful effects of drugs—and I know you disagreed with the original question, Dr Patterson—that it might be worth spending a bit more resources looking at that rather than looking at the beneficial effects once you get to the market?

  Dr Dollow: Someone who has a patient in front of them recognises that any prescribing decision is taken on the basis of the risks of the disease the patient is suffering from, the risks of prescribing the medicine and the benefits that medicine is going to bring. When we think about the evaluation of our medicines and safety, we have to take it in those contexts. We cannot separate them. People have recommended, for example, that safety evaluation be separated within the MHRA. I would, I think for clarity, recommend to the Committee that it is actually all within the MHRA but is in separate lines at the moment. We would support keeping it within the MHRA but ensuring that the safety and the efficacy are considered together.

  Dr Patterson: In terms of the things that are recognised as potential issues, either from the trials or from the literature, we do diligently follow those. I would give you an example. On Crestor which was mentioned earlier, on a weekly basis now I see a graph of the incidents and a report every week as to key events that may have happened, number of deaths, etc, and where that sits opposite the whole literature. That is worldwide on a weekly basis. Where it is an issue is where something is totally new; i.e it has not been described before. There it comes down to pattern recognition, which might come from a doctor seeing it in several of their patients and often comes from aggregating together experience over a number of trials for the development of longstanding trials in the course of the market place. That will always happen, particularly with the much less frequent side effects. If something happens one in a thousand, and you have 3,000 patients in your database or even 30,000 at the time of launch, unless it is unique, unless the drug turns your ears green or does something like that, it is unlikely to be picked out if it is a slight excess of something that the patient suffers from with that disease anyway, and you need large databases and long periods of time in order to pick it out. We do look for pattern recognition—that is what our SERM process does—but it sometimes takes 10 or 12 trials to be published before that comes together and the signal comes out.

  Q715  Mr Burns: The ABPI and its international equivalents have recently announced the launch of a clinical trials register. It is going to go further than the voluntary schemes currently in place. Do both of your companies support the setting up of a public register of all clinical trials registered at inception? Would you be happy to see it run by an independent authority?

  Dr Dollow: Our company is on record as going further than the current recommendations, so, yes, we would support that, both for results and from studies from inception.[16]

  Dr Patterson: All clinical trials, yes.

  Q716  Mr Burns: What about run by an independent authority?

  Dr Patterson: I do not think it matters. A register is a register, as long as the right information is there and it is only done once. We have a multiplicity of new registers appearing at the moment.

  Q717  Mr Burns: The pharmaceutical industry has told us how it wishes to work closely with government and the regulators. If such a relationship is attractive, why is it apparently that companies from time to time omit to give all the data at their disposal to the regulators or to NICE?—on the assumption that that statement is true.

  Mr Brinsmead: We, as a company—and it is the same for every company—would have to submit all of our data to regulatory authorities around the world, so I am not sure that is true.

  Dr Patterson: I think what you are driving at is the situation where maybe the work has been done outside the label of licence indication for a product, where the company is not applying for a licence for that indication. With a product coming to the market place for the first time, absolutely everything from everywhere is in there. When a product is out in the market place, people may use the product in other countries or of their own volition for things that are not part of the licence—and they may do that themselves. Once a product is there, any doctor can buy the product and use it or any hospital can use it for whatever they wish. We do not control that. If they then do that, we may not even have that information to provide it.

  Q718  John Austin: I wonder if I could come back to the question on Seroxat. You said in response to Dr Naysmith that there was a period when you changed your view from severe withdrawal symptoms being rare to acknowledging the real level, but is it right that the initial clinical trial showed a significantly higher rate of significant withdrawal symptoms than you were suggesting when you were suggesting they were rare? Why were you acting so defensively, almost in denial, when members of Parliament tabled an early-day motion a couple of years ago regarding the problems of withdrawal from Seroxat when you knew that there were significant symptoms?

  Dr Dollow: First, let me respond to the point about the level of withdrawal symptoms from one single clinical trial. That was a control which started putting people on several levels of Seroxat, so it started with 10, 20, 30, 40, which did not mirror clinical practice, and stopped them very abruptly. The levels in that one trial did not reflect the balance of all the evidence that was available from all the dossier that was submitted to the regulatory authorities. At the time that we put the information in our label about the discontinuation symptoms, that reflected the knowledge that we had and that reflected the knowledge that was available across the world. With regard to the evolution, we did not change our label at one point. The label evolves over a period of time, every time that it is being revised when there are safety updates and revisions to the licence. With regard to the early-day motion, I am afraid I do not have specific information about that, so I would probably have to get back to you on that.

  Q719  Mr Jones: You are multinational companies operating in the world market and Britain is a very small part of it. What importance do the changes our government might make in the way in which they regulate drugs have to you? Is it more as an example to other governments or is it important in itself?

  Dr Patterson: This is our home market for us. We have a third of our global research and development here; we employ some 10,000 people in this country. It matters enormously to us that this is an environment in which science is good, in which scientists can work in academic laboratories or in our laboratories with animals without fear; it matters to us enormously that the national health system is somewhere where we can do what is called translational research. We particularly focus our cancer work in this country and work with people who can then take those products into the early testing in man in a very well organised and scientific manner, and it matters to us at the end of the day that those people who have worked with the medicines in research are able to use them in the market place and able to talk to their colleagues globally about their experience with these products. So it matters.

  Mr Gray: I would support that it matters absolutely. I think I would also add that recommendations both from the Government and indeed from inquiries like this one also pertain to the very original questions that the Chairman was putting with regard to our reputation also. I think, therefore, we would take them extremely seriously.

  Chairman: Could I thank you, gentlemen, for an excellent session. We are most grateful to you.





16   Note by witness: GSK's position is that it supports both clinical trials results and studies from inception being available. All relevant information should be on such a register, and the register should be accessible. By whom a register is run seems to GSK largely immaterial. GSK does not rule out support for an independently run register, but remains unclear as to what advantage there might be, or are being claimed for such an arrangement, as compared to the existing position. Back


 
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