Uncorrected Evidence 503

1.	This is a corrected 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.

Oral Evidence

Taken before the Health Committee

on Thursday 18 October 2007

Members present

Rt Hon Kevin Barron, in the Chair

Charlotte Atkins

Sandra Gidley

Dr Doug Naysmith

Mr Lee Scott

Dr Howard Stoate

Dr Richard Taylor

________________

Witnesses: Professor Nancy Devlin, Department of Economics, City University, and Professor John Appleby, The King's Fund, gave evidence.

Q525 Chairman: I welcome the witnesses to the fifth evidence session in our inquiry into NICE. Perhaps for the record the witnesses will introduce themselves and the positions they hold.

Professor Devlin: I am Nancy Devlin. I am professor of economics at City University where I work at the city economics centre. I am also a senior associate at The King's Fund.

Professor Appleby: I am John Appleby, visiting professor at City University and chief economist at The King's Fund.

Q526 Chairman: To start, I ask a question of both witnesses: what does your research reveal about the cost-effectiveness threshold used by PCTs and how do you believe it relates to that used by NICE?

Professor Appleby: Perhaps I may first explain what the study is about. It is a very small feasibility study conducted jointly with NICE. The idea was to investigate feasibility. First, could we identify decisions made by PCTs either to invest or perhaps disinvest in new services? From that, could we estimate some sort of implied cost per QALY for the decisions taken? That is the background to the study. Clearly, it is linked to concerns of NICE, this Committee and many others about what the threshold should be and how much we are willing to pay to get health benefit from the NHS. We looked at only seven or eight PCTs and identified the decisions they made. We then chose some of the decisions to invest or disinvest and proceeded with the work. We found that in some cases we could estimate a cost per QALY; in other cases the decisions were based on the notion that a service which was to be introduced or not introduced was clinically more effective than anything else and cheaper, in which case it was dominant. We had very few observations and so I am not sure we can arrive at anything too conclusive about what the threshold is out in the real world in NHS decisions.

Q527 Chairman: Do you agree with that, Professor Devlin?

Professor Devlin: Yes. It was a feasibility study. The purpose of commissioning the study was to determine whether it would be possible in a larger study with more observations to identify the threshold that applied at PCT level. I think it demonstrated that that was feasible. It is not easy to do it, however. A lot of the decisions one observes are those where PCTs take what may be seen to be eminently sensible decisions either to disinvest in services which are very poor value for money or to invest in services which are extremely good value for money. It is easy to identify newly-added or newly-eliminated services, but that will not necessarily reveal marginal services and the willingness to pay at PCT level to gain a quality adjusted life year. One can certainly identify the services and assign to them a cost per quality adjusted life year gain, but a much larger-scale study would be required in order to come up with precise estimates of the binding thresholds that arise from PCT budget constraints.

Professor Appleby: We have to understand the position of PCTs here. They are going for relatively easy and more obvious things in terms of disinvestment. The sort of information we received was a fairly wide spread of values, which is what we would expect. In a larger study we would hope to start to identify more decisions and narrow that range, but it will always be a range; there will not be a single number out there on which PCTs operate.

Q528 Dr Naysmith: Professor Appleby, why do you think they are going for the easier things? Is it lack of information or do they just want to chop something quickly?

Professor Appleby: It is the low-hanging fruit argument, that is, if the evidence is fairly strong and something is clinically pretty ineffective there will not be much argument about it. Like NICE, PCTs can find themselves in a difficult position with their public and residents if they stop funding some service or whatever, so that is in the back of their minds.

Professor Devlin: I think that investing in services that are dominant and disinvesting from ones that are dominated is an entirely logical thing to do.

Q529 Dr Naysmith: One of the things we have recommended many times is that that is something NICE should do more of than in the past?

Professor Devlin: The other matter that has been observed and makes the research very challenging is that PCTs are not always well informed of some of the data that could support them in decisions regarding either investment or disinvestment. What slightly confuses the picture somewhat is that cost-effectiveness is not the only criterion that matters to PCTs, in the same way that it is not the only criterion that matters to NICE. Therefore, unpicking the basis of a decision that is made is also important.

Q530 Chairman: In evidence to us Professor Peter Smith suggested that the PCT threshold was likely to be nearer ₤20,000 than ₤30,000. Do you believe there is any robust evidence? Do you agree with what he says?

Professor Appleby: I think we have to be very careful. I emphasise that our study was very small and involved only eight PCTs. We looked at about nine different sorts of decisions that those PCTs had made. By the way, they were often the same decision. Some co‑ordination going on between PCTs in going for some of the same things. I do not believe from the evidence we have we can say one way or the other whether Peter Smith's figure is the right one or is correct in some sense.

Professor Devlin: There is no doubt in my mind that this is the sort of research that needs to be done to inform what NICE's response should be.

Q531 Chairman: In your evidence you more or less suggest to that in taking these types of decisions the NHS should have the equivalence of the committee at the Bank of England that sets the interest rate. Should NICE thresholds be more explicit, and who should set them?

Professor Devlin: There are two aspects to explicitness in a sense. One is the way in which the threshold is stated, whatever it is. What we have noted in our evidence is that there are a number of statements, which are inconsistent in very subtle ways, about what the NICE threshold is. They also emphasise the range and it is not always clear what the interpretation of that range is or, from the perspective of somebody who sits outside the NICE context, how that range is being applied in decision-making. Therefore, one aspect of explicitness is how the prevailing threshold is expressed. The other aspect of explicitness is that the threshold has no explicit basis or location in evidence. I believe that an explicit threshold should be both evidence-based and clearly expressed.

Professor Appleby: Together with Dave Parkins, who is also a professor at City University, we wrote a BMJ editorial on this matter. In our evidence to you we have said this is a fundamental issue that touches on what services the NHS should and should not provide and it goes to the heart of decisions about the willingness to pay to get benefit from the health service. As my colleague has said, some fudging going on as far as NICE and others are concerned not just about what the threshold is but how it is applied. There is no empirical evidence to support the threshold as stated by NICE; there is no real theory behind it, and yet it is such a fundamental issue. It is not just a technical issue in the sense of finding out some numbers and then deriving a threshold, crank the handle and that is it; it involves social value judgments and so on. We believe that either a separate independent organisation or at least an independent process can be set up by which the issues with which NICE and this Committee have been grappling are discussed, the research is commissioned and carried out and it is transparent. The public should also be involved because in the end it is an issue for them; it is their money that goes into the NHS and these are decisions to be made about how best that money is used. It is a finite budget. This decision will never go away no matter how much money we have.

Q532 Chairman: The article in the BMJ suggests in a sense that NICE is not as independent as it should be.

Professor Appleby: I hope we did not suggest that.

Q533 Chairman: I believe this is important in terms of this inquiry. What independence do people perceive NICE has?

Professor Devlin: I do not think this was intended to be critical of NICE. In a sense I think that NICE has been placed in an invidious situation. It does an excellent job at assessing the clinical and cost-effectiveness evidence in an enormously rigorous and diligent way. What we say is that the threshold that must be applied to make a judgment on the basis of that evidence is an extremely difficult issue. We are suggesting perhaps that NICE's threshold is not just a matter for NICE alone because it is not just NICE's business. If NICE makes a mandatory decision that PCTs must implement it completely alters the bundle of services which PCTs can afford to deliver. That affects the services that all patients can potentially consume or benefit from, so NICE's threshold should have an input from the sector and a much wider range of expertise.

Professor Appleby: NICE does an amazing job given the task it has been handed, but that job is more of a technical nature in collating and assessing evidence, commissioning research to fill gaps in that evidence and so on. But when it comes to the threshold that should be a separate job, as it were. We argued that maybe NICE should be handed a threshold to which it should operate rather than that at its inception it realised it could not do its job unless it had some sort of threshold at which point it said something was or was not cost-effective or that it did or did not recommend it. But at the moment that is buried in the work NICE does. Our argument is that it should be recognised as a separate matter and there are different ways to deal with it.

Q534 Dr Naysmith: What is the answer to the question put by the Chairman? Who should set the threshold and where should the decision-making process lie? If we are agreed that it should not be the department, where should it lie?

Professor Appleby: We suggested that the parallel should be the MPC. There could be a separate organisation, group or at least process and that would set the threshold. It is not just a one-off exercise; it will have to be updated every year. New evidence will emerge. The public's values - how much they are willing to pay and so on - will also change from time to time, so it includes a whole of things and it is an ongoing process.

Q535 Dr Naysmith: It is a good idea to say that somebody else should make the decision, but working out exactly who that should be is quite difficult.

Professor Appleby: Yes, but I am sure it is not beyond the wit of us to devise something.

Q536 Dr Naysmith: The Monetary Policy Committee is full of economists, bankers and so on, but do we want former trust executives or former Ministers on this body? Who should it be?

Professor Devlin: Perhaps it should be a range of expertise: economists and people involved in budget-constrained decisions in PCTs as well as people in NICE. I do not believe that the question of the appropriate expertise on such a committee is insurmountable.

Q537 Dr Naysmith: It is quite difficult to do.

Professor Devlin: It is not an easy question, but what we suggest is that it really requires a concerted effort that perhaps stands slightly outside NICE's remit. It is also a dynamic issue. A lot of the discussions around the threshold have tended to focus on either a single figure or a statement about a range. Those statements have been made since 1999. It is completely unfeasible that whatever the appropriate threshold or range was in 1999 is the same now. Regardless of what determines or drives that threshold, whether it is society's willingness to pay for a QALY or the threshold revealed by budget-constrained decisions, those factors will change year on year.

Chairman: In the end are we not talking about the terms of reference used by NICE? Clearly, if the thresholds were set outside and handed to NICE it would work to those thresholds.

Dr Naysmith: It does at the moment.

Q538 Chairman: Yes, but it does not admit it. What would be the change in reality?

Professor Appleby: I was trying to illustrate that in terms of what my colleague said originally about how the threshold to which NICE operates is difficult to define. There is no real evidence to support the threshold it uses, and the practice of using it is pretty fuzzy. I cannot now remember the numbers, but quite a lot of decisions are beyond the ₤30,000 QALY range that it recommends. I cannot remember how many but it is a minority. As far as I understand, NICE says that those are the circumstances where special factors come to bear. There appear to be an awful lot of special cases here which throw into doubt the range that NICE talks about. Therefore, there is an issue about making that more transparent. I suppose that it could be done through NICE. Perhaps one method is to change NICE's terms of reference, but we were thinking of taking it a step further and saying that NICE has another job to do, that is, just evaluations. It then applies a threshold which it is handed. I suppose that as a society we will never agree a single number, but at least we can get closer to what in a sense the public would like to see.

Chairman: What the public would like to see is an interesting concept. I would have thought that the wider range adopted by NICE is a case for the defence. If it decides that it is ₤50,000 a year it is quite happy that people should have it.

Q539 Dr Stoate: Whatever debate we may have about what the threshold actually is, there must be one. You have said that it is a range and it is interpreted in different ways. Is there any research evidence about whether the current threshold as it is applied is affordable? Do we know whether or not we can carry on like this?

Professor Devlin: Answering that question empirically is surprisingly difficult.

Q540 Dr Stoate: I thought it might be.

Professor Devlin: Obviously, there is a difference between what NICE might say about its threshold - because what we have been discussing so far is the means by which it expresses that threshold - and what it actually does. They may be two different things. In the evidence we provided to the Committee reference was made to a study also done at City University. That study looked at the thresholds implied by NICE's own decisions. They suggested that the actual threshold was considerably higher than ₤30,000 because of the number of special cases and decisions made in favour of drugs which were a lot higher than ₤30,000 per QALY.

Q541 Dr Stoate: But whatever the figure is do you have any research evidence that other treatments are being crowded out because PCTs have to provide these drugs whether they like it or not? Is there any evidence that other treatments are being effectively sidelined, marginalised and pushed out altogether because of NICE's decisions?

Professor Devlin: We were very interested in exploring this question. Methodologically, it is incredibly challenging because it is difficult to track through exactly what is crowded out as a result of the introduction of new products because of NICE-mandated decisions.

Q542 Dr Stoate: Clearly, there must be some evidence of it. Obviously, there is an opportunity cost for every new drug that comes in. If you spend money on one thing you cannot spend it on something else. As PCT budgets are effectively ring-fenced, as is the entire NHS budget, there must be a squeezing out somewhere. If you have to spend ₤1 million on Aseptin, for example, you have to find that sum from elsewhere. What work has been done to find out where that money has come from and what effect it has had on the wider NHS?

Professor Devlin: I do not think there is any direct evidence. You are preaching to the converted with respect to opportunity cost, and that would be an extremely interesting and important question to answer.

Q543 Dr Stoate: Why do you suppose no one has looked into it before?

Professor Devlin: I think that NICE guidance is a package of pressures that are binding on PCTs and include a wide range of targets and other imperatives that it faces. It is very difficult to disentangle any one aspect of that bundle of pressures and identify specific aspects.

Q544 Dr Stoate: But it is essential that we do. For example, how can the public decide whether or not they want a particular treatment if they have not understood the implications of other treatments?

Professor Devlin: What has to be foregone in favour of them? The only evidence of which I am aware in this context is anecdotal and it comes from consultants, reports in the media and things of that nature. As far as I am aware there is no hard evidence on opportunity costs associated with specific guidance.

Q545 Dr Stoate: That is of concern to me. The other matter that concerns me is whether there has been any modelling of the effect of future NICE decisions. If NICE goes on making decisions in future at the rate it is now making them is there any modelling on what the effect may be on PCTs?

Professor Devlin: Not to my knowledge.

Professor Appleby: There is very short-term "modelling". The Department of Health would claim that it makes an estimate of how much NICE decisions will cost the NHS in the next year or two, so that is as far as it goes. The figures we have had for England over the past four or five years have been in the ₤300 million to ₤400 million range. What the department says to PCTs is that when it makes its allocations part of the extra ₤300 million to ₤400 million is to cover this very issue, namely that NICE will be making recommendations and they will have to abide by them and commit funds to them. There is an opportunity cost in some sense, but existing services should not be stopped to fund new ones. That is the department's argument. It is almost universally believed in the NHS that that is not the case and that money is not ring-fenced but is notionally in the big lump of money that PCTs get. In our research with NICE we interviewed directors of public health and their colleagues in PCTs. We asked them questions about the effect of a decision by NICE and so on. PCTs will not directly link a decision that it takes about NICE with something else that it does. Every decision seems to be separate. The only evidence is anecdotal evidence from directors of public health. For example, a particular director of public health was very concerned about a cessation of smoking clinic which was stopped. He felt that that was a cost-effective use of the PCT's resources, but it was all mixed up with the then current climate of deficits and the need to cut back a bit. This was seen as a bit of an easy target; it was not affecting people's health today and so on.

Dr Stoate: The bottom line is that we do not know, and do not seem to have any method to find out, whether or not it is affordable. As a committee where are we supposed to go if we do not know whether or not NICE's decisions are affordable and do not appear to have any method of finding out? It is hopeless.

Q546 Charlotte Atkins: For instance, a number of PCTs do not fund IVF treatment despite the fact that they have a NICE guideline to say they should. Is that being crowded out or is some sort of value judgment made by PCTs that that is not the kind of service they want to provide?

Professor Appleby: I do not know what the decision of those PCTs is. NICE guidance is that it must be complied with. I do not know what excuse a PCT would have for not complying with that guidance.

Q547 Charlotte Atkins: Certainly the ones that you have investigated or observed have not disinvested from that sort of treatment?

Professor Appleby: Not as far as we are aware.

Professor Devlin: There is also a very complex issue specifically around IVF because the provision of that service across the country was already uneven prior to guidelines being issued on it. You may well have some PCTs moving towards it from different directions. Amongst our sample we had some that had altered the guidelines. It was not a question of whether or not IVF would be provided; there were more subtle ways to deal with it, for example in relation to the eligibility criteria but also the number of cycles that might be funded.

Professor Appleby: Often decisions were not that they had been funding the service but they then decided not to fund it at all. A lot of it came within the phrase "managed access". Therefore, PCTs came up with criteria which perhaps changed the age range for eligibility for a service, the severity of the illness had to be at a certain level before they would agree to fund and so on. There was shaving around some of the services. The service still existed but in a slightly reduced form.

Charlotte Atkins: My PCT has perhaps been slightly more honest in saying that it will not fund IVF treatment until it reconsiders it in the next financial year.

Q548 Mr Scott: Do you agree that if services are squeezed out and patients do not receive the treatment and drugs they need - indeed, if there is even loss of life - it is fundamental that such a report should be produced to show the effects?

Professor Appleby: I absolutely agree. The big assumption here perhaps is that everything the NHS currently does is absolutely great, is being provided efficiently and is of maximum benefits to patients. We should not assume that. Maybe some things are being crowded out because they need to be in that they are less value for money and so on. One cannot assume that all the NHS does at the moment is right.

Professor Devlin: I agree that much more evidence is required around that. In general, there is inferior evidence about the cost-effectiveness of a lot of what the NHS does compared with the kind of evidence that exists on the new drugs at which NICE looks. I believe that that is part of the challenge faced by PCTs. The cost-effectiveness of a lot of what PCTs commission simply remains unknown, so it is extremely difficult for them to make decisions about what should be foregone when confronted with an imperative handed to them by NICE.

Professor Appleby: That was reflected in another aside-type finding in our work. PCTs appear to spend an inordinate amount of time fretting about rather small amounts of money. They control hundreds of millions of pounds of NHS money, most of which flows straight to hospitals and other providers, yet PCTs set up exceptional panels to deal with individual patient cases and treatments because they have managed access policies and certain criteria have to be fulfilled. It needed almost all the time of a couple of directors of public health to deal with that. Some of the decisions might involve perhaps ₤50,000 or ₤100,000 and yet behind them millions of pounds were flowing through the system. It was something that we knew about. It is really shocking that that happens. In part it is to do with their resources. They do not have the staff, skills and so on, but they also do not have the information about cost-effectiveness.

Q549 Sandra Gidley: As a follow-up, has anybody looked at the cost of these panels and compared it with the cost of the technologies that they turn down? That might be quite an interesting study.

Professor Appleby: Yes. Nobody has looked at it as far as I know. All the PCTs we looked at, I think, devoted considerable amounts of time to it.

Professor Devlin: I believe that they are required to do so. There cannot be a blanket exclusion; there must always be a process around allowing exceptions. The management of that process is extremely time-consuming. We could perhaps talk of more general issues to do with the management of disinvestment generally. I absolutely accept what you say about the opportunity cost of NICE guidance which is crucial. There are also difficulties faced by PCTs in relation to disinvestment generally, not just what information should inform that, and also the sensitivities that surround any attempt to disinvest from any service.

Q550 Sandra Gidley: How can NICE encourage more disinvestment decisions because it appears that is part of the equation that is not being dealt with very effectively by anybody?

Professor Devlin: It can help inform those decisions. One of the aspects of PCT decision-making that we found was a desperate demand for information on what services were poor value for money, what should it be disinvesting from, what would be the appropriate responses to cost pressures and so on. We found instances of PCTs working together to try to create some sort of information and evidence base on which to do that. Clearly, there is scope to do that on a much greater scale to improve the information available to PCTs on matters that are demonstrably poor value for money that perhaps they ought not to be doing. Perhaps NICE or some other organisation can play a greater role in that. PCTs simply do not have the analytical workforce to make that sort of effort and it would be ridiculous for each PCT to duplicate it. Maybe some sort of clearing house to assist in and inform those decisions would be a good idea.

Professor Appleby: There is another bigger issue here about the state of commissioning within the system which is an apparent failure. I gave the example of PCTs worrying over relatively small amounts of money. One would hope they would be looking at their whole budget and making decisions on how to get the biggest amount of health and reduce inequalities with all the money they use. There is an issue about the inequality between the purchasers and providers in the system. The latter have a lot of power. Another issue to emerge from PCT decision-making was that cost-effectiveness might be a criterion but political acceptability was another. Could they get hospitals and others to change what they did? I believe there was a good deal of pessimism on the part of PCTs. They felt relatively powerless. They were the ones with the money which they handed over, but it was just flowing through the system as if they did not have much control over it.

Q551 Sandra Gidley: NICE is supposed to be doing some of this but it has done comparatively little. Should it do more? Should any disinvestment recommendations have the same weight as a new technology that is approved? Would that be helpful?

Professor Appleby: Yes. Relatively recently, they have set up or at least assigned some resource in terms of people and effort to look at disinvestments a little more thoroughly. It is much easier to introduce a new service or have more of something than to say it should be stopped, especially when the argument in the public mind is perhaps not that clear cut. The idea that if something is not killing you and may be doing you some good it is probably worth having is not how NICE or the NHS should operate. The area of disinvestment is a much more difficult area to go into, and that is why I believe PCTs need a lot more support. NICE could do more on that front, and I am sure it wants to.

Professor Devlin: The answers to your question are yes and yes. I think PCTs would find it enormously helpful if perhaps they were empowered to make decisions by having an evidence base to support them, whether that is provided by NICE or some other organisation.

Professor Appleby: NICE collects evidence but it is of an average nature and does not necessarily apply to a particular service in Colchester bought by a specific PCT. The cost-effectiveness evidence will vary from area to area and that is to do mainly with the way the service is provided. As we know, hospital efficiency varies. That is another issue for individual PCTs to grapple with. They may have evidence from NICE that something is cost-effective, but locally it may not be that cost-effective because of the way it is supplied. That means gathering data about the efficiency of local hospitals and so on. It is not simply a case of having a leaflet saying that it should buy this but not that. That is also where they need help.

Q552 Dr Naysmith: A good number of our witnesses and the evidence we have received suggest that there should be a lot more public discussion in a broad sense about the rationing of healthcare, healthcare facilities and so on. Do you believe that that should happen more, and can you suggest mechanisms by which it may be achieved? We all know about things that have happened in the past, for example the ranking of services and creating lists with mental health ending up at the bottom and heart surgery at the top. How does one get an open discussion about resources in the National Health Service and what can be done with them?

Professor Appleby: I absolutely agree with you. I hope we have made clear that the issue about the threshold is absolutely fundamental. I cannot think of a more fundamental issue to do with the NHS given the way it is funded and so on. It is not of academic relevance - I apologise for using that term pejoratively - but of absolute relevance to individuals in terms of the services they get and so on. It is their money, frankly, and they need to be involved in these things. I do not mean that necessarily they should be involved in decision-making in a fantastically detailed way, although there could perhaps be more room for that, thus bringing some of these issues to the fore, but they need to be aware of the decisions that the NHS has to take on their behalf. One idea at the back of our minds is the creation of an independent threshold-setting group. That would then bring these issues out into the open much more and lay out the trade-offs and difficulties. PCTs and the NHS are not bad people who are trying to deny treatment; they seek to do the right thing. NICE also tries to do the right thing in difficult circumstances, and people also need to understand that.

Professor Devlin: The involvement of the public has perhaps been seen as rather difficult. The idea of a cost-effectiveness ratio is not necessarily the easiest concept for people to come to grips with; nor is the idea of a quality adjusted life year, but perhaps more effort needs to be devoted to trying to explain those concepts in easily accessible ways, engaging the public in what is acceptable value for money. These debates should be more explicit and there should be more discussion on very difficult decisions, for example on third line cancer drugs that extend life by a month. What exactly should society be prepared to pay for that? What is a health gain worth? There are ways to express these things so that people can become engaged. I believe that it would help tremendously to try to get the public to acknowledge that when a new drug is developed it can be purchased and it can be benefited from, but that something else is necessarily foregone as a result.

Q553 Dr Naysmith: That is the crux of the matter, is it not? I quite liked Professor Appleby's earlier statement that NICE had almost a technical function to perform. It should say that something is value for money and its threshold for the value is such and such. There should then be another body that looks at it and decides that if that is to be paid for it will push out something else and not everything can be paid for. What should be the role of NICE in this rationing debate, if any?

Professor Devlin: I suppose the response to that depends in part on whether one believes that the threshold should be decided by NICE or a body somewhat external to it. Certainly, everything that NICE does provokes and informs that debate and provides an opportunity. Every time a new piece of NICE guidance comes out we receive calls from the media asking us to comment on what it means, what will be foregone and so on.

Q554 Dr Naysmith: Part of the problem is that some of the evidence is not that easy to use for the purposes of decision-making. You mentioned end-of-life cancer drugs. They will not say that they will prolong life for a month but that on average they will prolong life by between a month and three years. Maybe a month is not of much use, but many argue for three years and yet you do not know which it will be for you. That is a very difficult decision on that sort of evidence.

Professor Appleby: There is always uncertainty in these matters. There is an issue about what NICE looks at and what its agenda is, as it were. Why does it look at certain treatments and not others? Why is one treatment considered before something else? There may be an issue here about who sets NICE's agenda. In part, it is not just about individual treatments and cancer drugs, which are expensive and require decisions, but there are other things that go on in the NHS. For example, the dominant policy aim of this Government and previous ones has been to reduce waiting times. I am not aware of any figures to show how much money we have spent doing that, but it must run into billions over the past seven or eight years. That is a lot of health money to spend and it has an opportunity cost. I am also unaware of how many quality adjusted life years have been generated by that money; I have seen no research on that. There may be an issue here about at least demanding of government that in producing policy it also says something about the benefits and how much they will cost.

Q555 Dr Naysmith: If one goes down that route one will end up saying that the answer is democracy. One lays out everything one knows and then says, "You want to do this and you want to do that." That is where it ends up.

Professor Devlin: But that has to be facilitated by information and evidence.

Q556 Dr Naysmith: We are all agreed that more information is needed, but how do we get the discussion going? I agree that evaluating the worth of some of the more political matters is very important but it is difficult.

Professor Appleby: We have had cycles about the debate on rationing. For the past seven years it has gone a bit quiet. I suspect that that is because so much money has been coming into the NHS. There is perhaps a feeling that there is no need to ration; it has the money to employ people, to expand and so on. It will come back again. The NHS has a new settlement for the next three years, but it is less than half the real rate that it has received over the past seven years. That may focus some people's minds as well.

Professor Devlin: It is a very difficult debate to get going in the current climate. A big policy issue within the NHS has been improving patient choice. Patients should be able to choose what treatments they get, where and when. That sort of theme around responsiveness and individualisation of treatment alongside a debate on rationing in the health service is somewhat uncomfortable, is it not?

Q557 Dr Naysmith: Let me change the focus slightly to the level of the PCT. You will remember that primary care trusts were set up to reflect local needs. Each primary care trust would be able to use its budget to do what is best for its locality. NICE guidelines and directives remove that sort of ability and one ends up with a postcode lottery. Is there any way that we can incorporate NICE guidelines and advice and still reflect local needs?

Professor Devlin: My colleague touched on this earlier. Any piece of advice that comes down from NICE is based upon a cost-effectiveness ratio with evidence around both costs and improvements in health outcomes. Clearly, there are opportunities to tailor that sort of data to local settings to reflect different cost conditions, different patterns and modes of delivery and different epidemiology in a PCT. That sounds quite ambitious. Knowing what we know now about the way PCTs go about making their decisions and the nature of the evidence they have at their disposal, the idea that evidence is either widely used or is tailored in that way is an over-ambitious description of what is actually done.

Q558 Dr Naysmith: But if PCTs were obliged to explain their decisions to the local community and what evidence they used to make them and get feedback would it help?

Professor Devlin: Yes, absolutely, and they should do so. Some work has been going on in the Department of Health over the past few years to collect and publish information on the amounts of money PCTs spend on different disease areas. The national programme budget project has produced some very interesting information, not the least of which is to show the enormous variation in spending between PCTs. Even when account is taken of different needs and areas one still ends up with two or three-fold differences in spending on different disease areas. I believe that PCTs are hard pushed to explain why they are doing this but they should explain themselves.

Q559 Dr Naysmith: Should they have more local or public meetings or ask people how it should be done? They are appointed rather than elected bodies.

Professor Appleby: You may have attended some public meetings of PCTs.

Q560 Dr Naysmith: They are not the best attended meetings in the community?

Professor Appleby: The will to live almost ebbs away! They are not organisations skilled in engaging the public. Again, they are not bad people and they are not trying to hoodwink the public, but they just do not put effort into doing that and they should. You seem to be touching on the top-down aspect of NICE which was set up to deal with the postcode lottery, which was the phrase used when it was set up.

Q561 Dr Naysmith: I do not believe the term "postcode lottery" was used by the Government or NICE; it appeared in the press.

Professor Appleby: But the idea that one should not have differences between geographical areas in terms of access to services was one that arose at the time NICE was set up. In that sense PCTs are being told what to do, and yet they are also told to do their own thing, as it were, given their populations and so on. That problem has always existed in the NHS. The way that money is allocated through the weighted capitation formula more or less sets out PCTs' budgets, but it does not go any further than that. Those budgets are not ring-fenced in terms of how the formula works. All the PCTs get is a big lump of money that they can spend as they like which in part leads to variations in spending. That is a recognition that there is a national formula, as it were, which tries to deal with the desire for more equity in terms of access, but how far down the system does one go to tell it what to do? Presumably, we will not tell doctors to refrain from treating Mr Smith but to treat Mrs Bobbins. One cannot go that far. At the moment it stops at the PCT level. That is the organisation which has bottom-up decisions from clinicians and so on and top-down decisions from government and national organisations. They have to wrestle with that difficult issue and it seems to me there is no way of resolving it one way or the other.

Q562 Dr Naysmith: You talked earlier about how PCTs all around the country had some probably quite expensive special cases panels that met regularly and decided the same issue in different parts of the country. Is it not better to achieve that by deciding it nationally so that clinicians locally can recommend a particular drug? They have to carry the cost of it in their PCTs.

Professor Appleby: I do not believe so. The point about the exception panels is that they deal with individual cases, so a consultant may want to prescribe a particular drug which the local PCT says it will not fund except in certain circumstances. It is so detailed that they have to discuss the actual medical case of the individual with the consultant.

Q563 Dr Naysmith: But is it not possible to do something to deal with what are often very expensive and exceptional drugs?

Professor Appleby: That would be possible only if there was an indisputable common theme to do with age, say, but the point is that often there is a dispute between clinicians - they are autonomous, professional people who feel they are making the right decisions for their patients - and the PCTs who have the money and are able to fund it but who disagree. To put it politely, there is a discussion between the two. How that can be generalised I am not sure.

Q564 Dr Naysmith: Do you have evidence that there are different individual factors in different cases?

Professor Appleby: There is only anecdotal evidence from people I know and interviews with those involved in these panels.

Professor Devlin: In a way, that is the express purpose of the panels. It is almost like a safety valve for some of the disinvestment decisions that PCTs make. Therefore, the exception panels will consider special circumstances that consultants may wish to put forward. Some process needs to be there, but it is possible that some general truths, facts or evidence may arise from them which can inform either other panels or other disinvestment decisions more generally.

Q565 Chairman: In any health economy anywhere in the world have you seen citizen juries, as opposed to health professionals and/or patients, taking decisions about where expenditure should occur?

Professor Appleby: I am not aware of what other countries have done along those lines. I know that in England every now and then PCTs have used informed public opinion, as it were. A group of members of the public are presented with evidence by experts and discussions go on. That has fed into a decision by the PCT.

Chairman: That has happened in my own area. One has to decide what evidence is used in coming to these decisions and the views given in the papers presented to us and what you have said this morning.

Q566 Dr Stoate: We heard evidence last week that drug companies when pricing new drugs based their decisions on what the market would bear or, in layman's terms, what they could get away with. If NICE explicitly dropped its threshold do you think that would have a bearing on forcing down the cost of new technologies?

Professor Devlin: I believe that we commented on this in our evidence. One of the points about having an announced threshold is that it can inadvertently provide a target for pricing, so if there is evidence on the clinical effectiveness of a drug there is at least an incentive to price that product in such a way that it comes in at or just below the particular threshold.

Q567 Dr Stoate: Do you believe that goes on?

Professor Devlin: There is certainly an incentive for that to happen. I am not sure whether or not there is hard evidence that it happens in practice and, if so, to what extent.

Q568 Dr Stoate: You do not know whether if NICE explicitly dropped its threshold it would have any effect on the cost of new drugs?

Professor Devlin: In view of the particular circumstances that exist in the NHS there is a disconnect between the kind of assessments that are being made on value for money and the way pharmaceutical prices are regulated. Obviously, there are other health systems around the world that deal with it rather differently and, for example, harness to a greater extent the monopolistic purchasing power that a health system can have.

Q569 Dr Stoate: You are aware that most NICE approvals fall outside the fixed price tariff and are paid by results. Do you believe that the removal of the high cost exclusions under the tariff could help because it might mean that approved therapies would be covered by the tariff?

Professor Appleby: How is the tariff then derived?

Q570 Dr Stoate: If they are inside the tariff PCTs effectively would not have to bear the full burden of the cost; if they are outside the tariff effectively they are placed on the PCTs' budgets?

Professor Appleby: The tariff for paying hospitals is derived from the cost of hospitals. They would have to pay somehow. You may be suggesting that somehow the cost is spread.

Q571 Dr Stoate: That is what I am saying. The burden on individual PCTs will be less acute.

Professor Appleby: The short answer is yes, maybe.

Q572 Mr Scott: The report of the Office of Fair Trading recommended a system of value-based drug pricing. Is the data available at launch robust enough to allow value-based pricing judgments?

Professor Appleby: The short answer is that I do not know.

Professor Devlin: I suppose that the evidence to which you refer is related specifically to health outcomes.

Q573 Mr Scott: Yes.

Professor Devlin: The evidence generated about health outcomes is that which informs the decisions in terms of cost-effectiveness. In a sense, if the evidence is good enough to make a judgment on the grounds of cost-effectiveness arguably it may also support decisions on value-based pricing. The danger is that that evidence especially for new drugs is generated only within the context of a clinical trial and often very little is known about the outcomes for patients when a drug is used in a real setting as opposed to a clinical trial. Obviously, there are clear limitations that need to be taken into account in using that evidence, as is also the case when making use of that evidence to make a value-for-money assessment.

Q574 Mr Scott: What I am getting at is that sometimes we learn from the media that a drug will prove to be a wonder cure for x when tragically in reality it will not, and perhaps some more robust investigation will deal with that problem?

Professor Appleby: One cannot disagree with the general principle that the NHS should maximise health for the money it spends. Investigating any way of making that happen is perhaps worth doing. There are issues about the practicalities of value-based pricing. For example, you have to collect information about health over a long period of time to see what the value is. Clinical trial data is just that. We know that when therapies are used in practice often they will be used on different populations and will be delivered in different ways and not exactly in trial conditions. All of those things will perhaps affect outcome. Having said that, it may be no bad thing to collect the sort of information that would be necessary for value-based pricing. Evidence about changes in people's health status as a result of receiving healthcare on a continuing or routine basis would provide valuable information for lots of things, including perhaps value-based pricing.

Q575 Mr Scott: The SMC relies on cost analysis provided by manufacturers when making decisions, yet its decisions are almost always consistent with those of NICE. Does NICE really need the complex system of consultation and draft guidance that it currently employs?

Professor Appleby: One matter to bear in mind is the complete timescale involved from somebody having an idea about a new therapy or drug through to NICE saying that it is a good buy. NICE's decision are at one end. An awful lot of time is spent on doing other things, for example testing the drug and so on. I do not say that that should be cut back, but we should keep it in context. Clearly, there will be an opportunity cost to NICE shaving or abandoning its pretty sophisticated consultation process. There may be an outcry that it is not taking it out to enough people and so on. I do not know the answer, but clearly it would be good to minimise the period that NICE takes to review something. We should not forget that there will be some cost to doing that.

Professor Devlin: That is a very good question and it depends in part on the value that is placed on the process. That is a very difficult matter. My personal view, which is no more important than anybody else's, is that NICE's process is superb and internationally it is an outstanding example of how evidence-based decisions should be made in the public sector. The process of thinking about what the threshold should be is just an extension of that; it sharpens it up and makes it more transparent. I believe that it would be a loss to work backwards from that.

Chairman: Thank you very much for the evidence both written and oral that you have submitted to the Committee.

Witnesses: Dr Beverley Hunt, Medical Director, Lifeblood: The Thrombosis Charity, Professor Roger Atkins, British Orthopaedic Association, and Dr Anita Thomas, Chair of the Chief Medical Officer's VTE Implementation Working Group, gave evidence.

Q576 Chairman: I welcome you to the fifth evidence session of the Committee's inquiry into NICE. Perhaps for the record you would introduce yourselves and the positions that you currently hold.

Dr Hunt: I am Dr Beverley Hunt, medical director of Lifeblood: The Thrombosis Charity which I co-founded in 2002. Our aim is to increase awareness of venous thrombosis and improve the amount of research funds that go into it. Am I allowed to continue by explaining a little about the work of the previous Health Committee?

Q577 Chairman: I believe that will arise as we develop this particular session.

Dr Thomas: I am Dr Anita Thomas, a consultant physician in acute medicine in Plymouth Hospitals NHS Trust. I currently chair the Chief Medical Officer's VTE (venous thromboembolism) implementation working group. I was chair of the independent expert group on venous thromboembolism. I apologise for something that I am not. Your leaflet says that I am on a NICE appraisal committee. I am not.

Q578 Chairman: And never have been?

Dr Thomas: No.

Professor Atkins: I am Professor Roger Atkins, a consultant orthopaedic surgeon from Bristol. I am here as the British Orthopaedic Association lead for NICE. I represent the British Orthopaedic Association and specialist societies such as the Hip Society, Knee Society and British Trauma Society.

Q579 Chairman: I know that some of us have met Dr Hunt in her lobbying of Parliament in relation to this subject-matter. Most commentators praise the clinical guidance of NICE. Why did not its normal processes work for the VTE guidelines?

Dr Hunt: I am a member of a NICE guidelines development group which is for the next set of guidelines on thromboprophylaxis. I very much appreciate NICE. We have to have NICE. It is an excellent institution, but I think we need to change the process. The process is not without flaws. If we consider the process of producing clinical guidelines, some of the problems have been exposed by the recent guidelines on the prevention of pulmonary embolism in hospitalised surgical patients. From the perspective of experts in venous thromboembolism the problem is that the process does not use experts well. If we consider what happens to the clinical guidelines, they go out to scoping and at that time there is a consultation with experts and interest groups. They decide what they will do and that then goes to the guidelines development group. That group uses information scientists and statisticians who analyse the evidence available and then present it to the clinicians on the committee. The problem is that on that committee there are no experts. There are clinicians who are very well meaning and intelligent; they are all good eggs, but they do not have expertise in the area. Therefore, they will review what the statisticians have said and come out with an answer which is usually there or thereabout, but they do not have an understanding of the nuances or the papers in the area. I believe that the recent guidelines on the prevention of venous thromboembolism in surgical patients highlights that. They analysed the same data set as all the other international guidelines in the area and also the independent expert group set up by the Chief Medical Officer and came out with a different answer. Everybody else in the international community would recommend pharmacological thromboprophylaxis if somebody was going to hospital and needed some form of prevention against DVT. That would be the first one. The NICE guidelines recommend mechanical methods, that is, perhaps just a pair of stockings. How it emerges is that in this country if you are a patient between the ages of 40 and 60 and you have a major operation but are otherwise well - you may be a woman having a hysterectomy or a man having a gall bladder removed - under the NICE guidelines you get a pair of stockings but anywhere else in the world for five, six or seven days blood thinners are injected. What does this mean? It means that if you use pharmacological methods the statistics show that the death rate due to pulmonary embolism is reduced. There are no studies to show that you reduce the death rate with a pair of stockings. This has a good deal of impact on patients. The suggestion in my written evidence was that NICE should consider the use of an expert from the area as a member of its guidelines development group. I think that it chooses not to use experts because it is concerned about a conflict of interest, for example it may have funding from pharmaceutical companies. I recommend that if somebody is earning perhaps more than 10% of gross salary or has grants totalling more than ₤100,000 he should be excluded from the panel, but NICE certainly ought to have an expert on board so it can understand all the nuances of the papers.

Dr Thomas: In order to shine some light on this area we need to go back to the beginning and follow how we got to this position. It began with this Committee's work and the seminal report that it produced about the prevention of venous thromboembolism. The Committee drew attention to the 60 potentially avoidable deaths every day and the estimated ₤640 million a year this condition cost the NHS. The Government responded very rapidly to that report and set up the independent expert group having consulted NICE about the production of guidance and the timeframes over which guidance might be produced for different groups of patients. It was clear that the independent group convened by the Chief Medical Officer had a broad remit, including measures to do with implementation of guidance as well as "to review existing guidance in totality and in the main". It was agreed at an early stage that NICE would deal with a particular group of patients in hospital, those being high risk surgical and orthopaedic patients. The independent group produced its report which was published in April 2007 and at the same time the Chief Medical Officer wrote to all doctors with a summary of the guidance and the recommendations produced by the group. Both the independent group's report and the CMO's letter referred to the fact that NICE would be producing guidance on high risk surgical and orthopaedic patients. We are now at April 2007. Looking back, I presented the report to the Chief Medical Officer in 2006. At that time NICE was consulting and thinking about the process for its broad and wide-ranging consultation on venous thromboembolism. I believe that was published in November 2006. The result of that consultation was a broad set of replies, many of them detailed. One of the replies was from the Department of Health itself. It is important to note that the title of the document that went out for consultation was "High Risk Surgical and Orthopaedic Patients". It is perhaps also important to note that the Department of Health's response to that included a concern that NICE should stick to its remit of high risk surgical and orthopaedic patients in order to avoid any potential confusion for clinicians and patients in due course. In the event, in April 2007 the Chief Medical Officer published the report on venous thromboembolism prepared by the independent group. The earliest time that I learnt that there had been a change in the title was during a teleconference in April with NICE and Department of Health/NICE liaison officials. It became clear that the title of NICE guidance had been changed after the period of consultation to "Patients Undergoing Surgery", ie all in-patients undergoing surgery. This was also news to Department of Health/NICE liaison officials and I do not believe that it was possible for those officials to see NICE's guidance or recommendations before they were published. However, there is always tomorrow. I believe that the focus now both nationally and internationally is not on guidance because, as NICE has itself said, guidance is just guidance, and any member of this Committee would expect his or her doctor to make an informed decision in his or her best interests. In its own press release NICE has indicated that now we are turning to the implementation phase it will work closely with the implementation working group announced by the Chief Medical Officer on behalf of Ministers in the independent group's launch of its report. We know that even in moderate to high risk patients less than one in 10 receive thromboprophylaxis, so the focus now of both NICE and the implementation working group is on measures for prevention and risk assessment. This disease is silent. Very few cases are diagnosed before death; 80% to 90% are diagnosed after death, yet it is easy to predict. The issue is about identifying who is at risk. As a patient you have the right to ask what will be the risk and what will be done about it. There are effective methods and whether they are pharmacological or mechanical or other depends on the precise clinical situation at the time. The focus now is on implementation of risk assessment strategies across every hospital. Certainly in England, the question is: what is the risk of a particular patient developing VTE and what is to be done about it?

Q580 Chairman: We are not having a hearing on VTE as opposed to the issue of NICE, but I understand what you say. You will be pleased to know that that is now on the record. Professor Atkins?

Professor Atkins: Sticking to the critique of the NICE process, the first point to make is that the guidance was prepared under the heading of cardiothoracic surgery. I was asked by the president of the British Orthopaedic Association to take on the lead role for NICE in about September of last year. The orthopaedic community did not know that a VTE guidance document involving us was being produced. I scanned the NICE website at great length and that document did not appear as a musculoskeletal document. I discovered it only by accident, and with some surprise, when I deliberately opened it to see what NICE was recommending for cardiothoracic surgery. In generating the document NICE gave the role of looking at guideline development to the National Collaborating Centre for Acute Care. NCCAC barely had any orthopaedic input and the only person who sat on the NCCAC's guidance development group was an orthopaedic surgeon with no specific knowledge of venous thromboprophylaxis. According to him, he was not asked to comment on thromboprophylaxis in orthopaedic surgery. When we received the draft document at the turn of 2006 the BOA, specialist societies and the group I chair wrote a 17-page document of commentary, including the latest evidence, and received no reply. We emailed the chairman of NCCAC on a number of occasions and received no reply. When the final document came out in April we immediately started to approach NICE to say that it had simply got it wrong. It took until June before we could have a first meeting. At the beginning of that meeting the impression I gained from NICE was that it simply did not believe that orthopaedic surgeons collectively had any interest in this area or that they could possibly have come up with a scientific critique of its methodology. Having surmounted that barrier, with the realisation that we were able to critique its scientific methodology, in which there were very significant flaws, it took us until October to have another meeting with NICE to find a way forward to resolve the issue. It does not seem to have a mechanism to review its guidance once it has been published to address the very real concerns of clinicians. That is the critique of its process. Against that background, we thoroughly agree with most of what is in that document. Patients should be assessed for VTE. One should do everything in one's power to stop them getting venous thromboembolism. We have been doing this for the past half-century. I can go through the critique of its scientific methodology, but I am not sure that is what you want to hear because it is highly complex. In outline that is our critique of NICE's process.

Q581 Dr Taylor: I should like to concentrate first on the NICE process. Here we have a practising orthopaedic surgeon, a practising physician and a practising haematologist all of whom agree that the process is not exactly superb as described by Professor Devlin in the previous session. Dr Hunt, in your written evidence you go as far as to say that the way in which NICE formulates its recommendations can lead to flawed, capricious decisions. Professor Atkins, you have significant concerns about the scientific basis. The orthopaedic community was not adequately consulted, and there does not appear to be a robust mechanism by which your concerns can be transmitted. It appears that all of you condemn the lack of expert advice that is provided to NICE. Is that a fair summary?

Dr Hunt: This is not new. I read the Health Committee's 2002 report on NICE. I quote: "Medical consultants have said they find it staggering that treatments are being appraised by clinicians who have no working understanding of the clinical areas they are investigating." That really says it in a nutshell. We have very good clinicians reviewing evidence, as they are trained to do, but do not understand the data and nuances of all the different studies, so they will not be able to weigh up whether this is a good study or that is a bad study. Therefore, we end up with different results from others who review data. The American College of Chest Physicians who produce the gold standard guidelines in the area use 87 international experts in venous thromboembolism to come up with its guidelines.

Q582 Dr Taylor: You say that the thrombosis experts in this country are a tight-knit group; they all know one another. Therefore, you know that none of them was involved at all?

Dr Hunt: No, they were not.

Dr Thomas: I have not commented on NICE's process outside what I have said about the problem with the handling strategy agreed between NICE and the Department of Health. I do not have any knowledge of the NICE process and have not been as involved as others.

Professor Atkins: I agree entirely with Dr Hunt. There are major orthopaedic experts in venous thromboembolism and they were not involved. Perhaps I may quote your previous report concerning obstetricians: "An essential element in the widespread acceptance of these guidelines within the obstetric community was that they were introduced and supported by obstetricians themselves." The orthopaedic experts who have dedicated 20 to 30 years of their lives to getting rid of this scourge from orthopaedic surgery without producing unacceptable complications were simply not involved.

Q583 Dr Taylor: Therefore, one of our strongest recommendations to NICE must be that it employs experts?

Professor Atkins: Yes. The timescale for this is right this minute. Just three days ago I was sent a NICE email about the next guideline development group on VTE. One again, in its remit it has orthopaedic and trauma in-patients; it has not put an orthopaedic experts on its guideline development group. There is nobody there to represent orthopaedic surgery.

Dr Thomas: Just to illustrate, when I rambled earlier I should have explained one of the issues I would be concerned about in looking at NICE process. During the consultation responses the Department of Health said that it was concerned that NICE did not appear to be taking the opportunity potentially to save lives. NICE appeared not to hear that. Although the process of consultation is, I am told, very broad, wide-ranging, complex and intensive, whether or not the responses are acted upon or listened to I do not know, but in respect of VTE the department's response was not acted upon.

Q584 Dr Taylor: I take you back to what you said earlier about the change of remit. Can you go through that again to make sure we absolutely understand it? At the beginning it was to be just guidelines on high risk patients who were undergoing orthopaedic and general surgery?

Dr Thomas: Yes.

Q585 Dr Taylor: What has it been changed to?

Dr Thomas: It has changed to all in-patients undergoing surgery.

Q586 Dr Taylor: What change does that make in effect?

Dr Thomas: In effect it includes the low and intermediate risk groups which were the subject of an analysis of the convergence of existing evidence in our report.

Q587 Dr Taylor: Dr Hunt, I think you made the point that your relatively small charity is spending a lot of money making representations?

Dr Hunt: If one has a group of people who are not experts producing guidelines one of the considerations is that one is allowed to consult after the draft stage. We spent a huge amount of time going through the guidelines and pointing out all the faults. I know this was done by a large number of people. It would be much more sensible to have experts on the committee in the first place so we do not have to do this large critique. We are a small charity and we must deal with the whole of the United Kingdom. Human bodies work the same whether they are in Northern Ireland, Scotland, England or Wales. Why can we not have the same guidelines for every region? NICE covers only England and Wales; SINE covers Scotland; and Northern Ireland usually follows the NICE guidelines. Why cannot NICE cover the whole UK?

Q588 Dr Taylor: How are we to convince NICE? I think I am right that in talking to us it has said it does not want experts because it believes that they can be biased.

Dr Hunt: I think it is very concerned that experts can be tainted because the average expert has dealings with pharmaceutical companies. It can be argued that one cannot be expert unless one has dealings with pharmaceutical companies. One sits on a drug advisory board when they are developing a new drug and they will be asking for one's opinion about it and presenting it. One can start to see the flaws in the drug. When one goes out to do a lecture one can say that a new drug is coming along and give a balanced view. In a way, there is a necessity to have some links with the pharmaceutical companies. Clearly, there must be a personal pecuniary limit on how much money anybody can make from that type of consultation. Therefore, I suggested in what I wrote that there should be a limit so people could not earn more than a certain amount, and they should not have grants from pharmaceutical companies. There is much more danger of bias. If we allow experts to declare in a conflict of interest statement where their interests lie it is clear how they might be pulled.

Q589 Dr Taylor: Effectively, we have international guidelines, the expert panel and NICE all saying rather different things?

Dr Hunt: Yes.

Q590 Dr Taylor: How do practising clinicians cope with that?

Dr Hunt: When NICE was set up in 1998 there was a document called A First Class Service which said that the aim was to produce clear, credible guidelines and end confusion by providing a single national focus. We are not doing that at the moment in this particular field. People are muddling along and are confused. They have too many guidelines coming at them saying different things and so there is inertia. The real worry is that we are not getting any thromboprophylaxis.

Dr Thomas: What must be avoided at all costs is the situation we saw in which the Chief Medical Officer wrote to all doctors in the UK with guidance and within a week, because of a last-minute change of title, NICE appeared to contradict the CMO. Clinicians have always enjoyed an abundance of guidance. There is a point in time when that is brought together. My colleague Dr Hunt as a clinical expert has already referred to her role in the NICE guidelines development group which is considering all patients. One can just hope to gain some measure of reassurance from an understanding that NICE will take account of all current and any other upcoming international guidance as well as the guidance in the letter of the Chief Medical Officer and the report of the independent group. Perhaps NICE will get it right next time.

Professor Atkins: From the orthopaedic point or view the answer is slightly complex. First, although the guidelines of the American College of Chest Physicians are excellent for many things they are incorrect as regards orthopaedic major surgery. That is the universal opinion. That is not just the opinion of the British Orthopaedic Association but the opinion of the Canadian, Australian, South African and New Zealand orthopaedic associations. All the heads of the European orthopaedic associations agree that ACCP has it wrong. The reasons for that are quite simple and, if you wish, I can illustrate them. As a result of that and with the agreement of the international presidents of the orthopaedic associations the American Academy of Orthopaedic Surgeons commissioned a further set of guidelines which were prepared in a robust process that deliberately included both independent epidemiologists and orthopaedic VTE experts to produce what I suppose we would all call a gold standard document that is now available. Reference to that document will now be made by orthopaedic surgeons because it has it right. That document's final conclusion is that chemical prophylaxis does not improve death rates following major orthopaedic surgery. That is the sum of evidence. I do not want to go into that any further, but the way forward is the use of the national joint registries to register each of these major operations and inquire what the risk of death and complication is and improve year on year outcomes with respect to death from both VTE and other problems. I think that is the way forward.

Q591 Dr Taylor: This shows an absolute failure of NICE. Obviously, there is a disagreement between the orthopaedic people on one side and the thrombosis experts on the other, and this is just what NICE should have resolved?

Dr Hunt: I do not think there is a difference between us. One of the problems with the NICE process is that one looks only at randomised controlled studies, as do a lot of the other international guidelines. Professor Atkins is talking about a data set where a lot of the information does not come from randomised controlled studies. Orthopaedic surgeons have access to data that is not in the other guidelines, and it would be very good if NICE could widen its scope and include that type of data. It brings me to the other point that it is very fond of using something called mixed meta-analysis. That is a technique whereby one lumps together a whole load of studies and analyses them. One does not have enough patients in each group; one needs 10,000 and so one puts them together. In the VTE guidelines it tends to lump together stockings and pneumatic compression, that is, balloons squeezing legs. A purist would say that that is not really very good and one should not be lumping them together but analysing them separately because they are different techniques. If an expert was on the panel he would say that.

Dr Thomas: The world moves on. There continue to be advances in our understanding of what is and what is not effective. Indeed, there are new agents coming along within months to years which can be taken orally. Again, the guidance will have to be revisited in the light of developments. It is important to acknowledge that the target is a moving one.

Professor Atkins: There is no disagreement amongst us. There are inevitably differences in emphasis. I am focused totally on orthopaedic surgery and would not dream of passing a comment on any other area.

Q592 Dr Taylor: We can take it you are all agreed that risk assessment should be mandatory?

Professor Atkins: Yes.

Dr Thomas: Yes.

Dr Hunt: Yes.

Q593 Dr Taylor: Is there any evidence that PCTs are trying to force this through, or that anybody seeks to push it?

Dr Thomas: As part of the Government's implementation strategy for VTE we are working with exemplar centres, as I believe Dr Taylor is aware. Through those centres we see examples of good practice. We do not yet, but hope to soon, have a commissioning PCT interested in becoming an exemplar centre, but I cannot say any more at this point because we are in the early stages of discussion.

Q594 Charlotte Atkins: Dr Hunt, you spoke about experts possibly having a conflict of interest and you came up with a formula that might overcome that issue. Do you think that if instead of having experts on the panel as full members they acted as expert advisers that would overcome the problem, or not?

Dr Hunt: It depends on how they are used and the quality of the chairman. The other issue is: how does one define an expert? It is a very loose term, is it not? It needs to have a tool whereby it defines an expert as someone who has produced more than 20 clinical papers and maybe has an active research group and is lecturing in that particular area. Because the NICE process takes probably two and a half years it is more sensible for the experts to be members of the guidelines development group rather than maybe just attending one of the sessions. They can have a more ongoing discussion within the group about how to analyse the data.

Q595 Charlotte Atkins: For instance, this Committee has advisers who stay with it for the whole period of an inquiry and they advise it and give it the value of their expertise. What I suggest is that to overcome any possible conflict of interest experts, however they are defined, can simply be professional advisers to the committee.

Dr Hunt: What you describe is an excellent idea. I had not thought of it in that way. You have someone there for most of the process but he or she is not a member of the committee but sits in. It sounds a very logical way forward.

Q596 Charlotte Atkins: Dr Hunt, you referred to problems with randomised controlled trials. Do you believe that NICE has got it completely wrong and it must adopt a less biased approach to the way it conducts its appraisals?

Dr Hunt: It does not have it completely wrong. I very much admire NICE and I am part of the process. I have signed up to the process, but it just needs tweaking round the edges. It needs to look more widely perhaps at the data out there. Certainly, for thromboprophylaxis there is quite a lot of data that is not available from randomised controlled trials and it is just put to one side in the analysis. Maybe it should consider looking at it.

Q597 Charlotte Atkins: Professor Atkins, what is your view?

Professor Atkins: One of the difficulties of not having orthopaedic surgeons directly on the panel is that the RCTs are not level one evidence in the sense that what we are interested in doing is improving our patient outcomes. The endpoint is: do the patients survive or die? The RCTs look at a surrogate of a surrogate. The evidence that that surrogate is applicable in orthopaedic surgery today, as opposed to 25 years ago, is not there. Therefore, the RCTs may be worthless. One must have broader and much more informed view of the science out there and one can get it only by having folk who are truly expert. That means that not only are they researching the area but doing the work on the ground. Year on year we change our surgical technique to improve patient outcome, so data adduced 10 years ago is today almost worthless.

Q598 Charlotte Atkins: Do you believe that NICE is not providing the right balance between technology appraisals, procedure and clinical guidance? Do you think that it is just not getting it right, or is there some way that they can make progress?

Professor Atkins: If we broaden it slightly, in this case NCC delegated to NCCAC the process of guideline development. My view is that NCCAC's process is badly flawed and NICE does not appear to have had sufficient oversight of what NCCAC was doing. If one broadens it out to technology appraisal, NICE needs more expert advice from the orthopaedic community. The statistics of orthopaedic surgery are incredibly arcane. If one looks through the NICE technology appraisals, many of which are very good, there are some really bad statistical howlers which it would have got round had it had proper orthopaedic expert advice. If one puts the orthopaedic experts on the committees the orthopaedic community will take ownership of the guideline and implement it. To me, that is why it is essential to have the experts there. I just do not believe that the business about a conflict of interest is a real issue.

Q599 Charlotte Atkins: So, they should be full members of the committee rather than advisers to it?

Professor Atkins: Definitely, yes.

Q600 Dr Naysmith: Do you believe that as a result of these guidelines there is anybody who is being given faulty treatment because somebody is following them; in other words, someone is not getting thromboprophylaxis and is being fobbed off with elastic stockings?

Professor Atkins: In orthopaedic surgery the problem is the obverse. The NICE guidance came down heavily in favour of chemical prophylaxis. The evidence from the AAOS studies, national joint registries and modern data is that the use of chemical prophylaxis is not associated with either a reduction in readmission to hospital for venous thromboembolism compared with folk given no chemical prophylaxis or a reduction in death rate, but it is associated with a significant increase in complication rate from the side-effects of bleeding. The concept that orthopaedic patients are not given thromboprophylaxis is absolutely wrong; all of them are. Over 50 years we have reduced the rate of death following total hip replacement due to venous thromboembolic disease from 4% in the 1960s to the current rate in Bristol of zero.

Q601 Dr Naysmith: I am glad to hear that!

Professor Atkins: If we start to put patients on the NICE guidance we cannot improve on zero but we can give them complications of bleeding, which is what will happen.

Dr Naysmith: Thank you for that very clear statement of the position.

Chairman: I thank all three witnesses very much for coming along to give evidence this morning.

Witnesses: Mr Steve Winyard, Campaigns Manager, Royal National Institute of Blind People, and Dr Rafiq Hasan, Director of Market Access, Novartis, gave evidence.

Q602 Chairman: Welcome and thank you for coming here to take part in the fifth evidence session in our inquiry into NICE. Perhaps for the record you would give us your names and the positions that you hold.

Dr Hasan: My name is Rafiq Hasan and I am director of market access at Novartis Pharmaceuticals in the UK.

Mr Winyard: I am Steve Winyard, head of campaigns at RNIB.

Q603 Chairman: We said to a previous witness this morning that we tend to meet you on occasions in Parliament. Whilst there is no direct financial interest we meet you via back-bench committees and other ways to talk about the issues that we intend to discuss today. I am not sure whether that is a declaration of interest on my part, but I think I should say that. Industry complains that in the UK the take-up of new drugs is slow and variable and policymakers complain that clinical guidelines are often ignored by practitioners. How can that problem be mitigated?

Dr Hasan: As you have already heard this morning, there is quite a lot of variation across the country in terms of PCT uptake of new technologies. We heard this morning about exceptional case committees that often put in place what we see as hurdles and barriers in the way of patients getting access to new medicines. If one takes the case of Lucentis, a drug that is currently being appraised for wet AMD, the clinical evidence suggests that over 70% of patients experience an improvement in vision. Before that drug was available these patients had virtually no other effective treatments that could have such a significant impact. What we see is the whole concept of NICE blight before NICE has made a decision. Once NICE comes out with some final guidance we see slowness in uptake and implementation.

Q604 Chairman: we may want to cover that a little later. Mr Winyard, do you have any general comment?

Mr Winyard: RNIB's involvement in the NICE process is fairly limited. We have engaged in only two appraisals and my comments will be based largely upon that experience. Involvement in the work of NICE, however, is very important. One of our royal charter objectives is the prevention of blindness. We know that sight is precious to people. If you ask your constituents nine out of 10 will say that sight is a sense that they most fear losing. For a very long time there were no treatments for wet AMD and that accounts for about half of all new blindness registrations in the UK, so it is the big cause of blindness. For RNIB, when new approved safe treatments have become available in the past two years our trustees have tasked us with making sure that they become available on the National Health Service. That is why we are involved. The other general point to make is that our primary relationship in all of this is with the Royal College of Ophthalmologists and in a sense it would be great to have the college here because it has the expertise on these issues. The president of that college is on our policy and advocacy committee which lays down what our policy will be on different treatments. In terms of access, obviously there is an enormous problem between the time a drug gets EMEA - European - approval and getting NICE guidance. At the moment we are right in the middle of that. Amongst the members of the Committee, we note that in some areas - in yours, Chairman - patients will be treated but in others they will be turned away. For example, in Staffordshire there appears to be a blanket ban on treatment, and in many areas patients have to go blind in one eye before the primary care trust will consider treating the second. This is fundamentally wrong and we have to find a way round it. In the short term, together with the Macular Disease Society we have established an advocacy service funded by Novartis and Pfizer which supports patients who contact us via our help lines and say they are going blind; they have paid into the NHS all their lives and the first time they draw on it they are turned away. They are told that they cannot have funding. In those cases we support patients and engage with the primary care trust; and we also engage with MPs. We are trying to apply sufficient pressure to ensure that patients get treated. It is not an ideal situation but it is one that we face. It all comes back to the prevention of blindness which is our royal charter objective.

Q605 Chairman: If I may ask specifically about patchiness in terms of the implementation of guidance, what do your members think about it? Yours is a membership-based organisation.

Mr Winyard: We are indeed. There is enormous anger and frustration that there is such wide variation. If you are fortunate to live just over the border in Cheshire and Merseyside both eyes will be treated, whereas if you are in Staffordshire you will be turned away. There is anger, frustration and a sense of real unfairness. That has been reflected in the very high level of media interest when local and national cases emerge.

Q606 Dr Naysmith: Dr Hasan, you suggest in your written evidence that the quality of work carried out by some of those who produce assessment reports and others who may review the evidence is both questionable and variable. That is quite a serious accusation. Can you give us some examples?

Dr Hasan: I think it comes back to the whole discipline of health economics which is embryonic relative to clinical medicine, randomised controlled trials and evidence-based medicine. When we assess health economic outputs we must understand that there is a high degree of uncertainty. The point we made in our written submission was that when NICE commissioned independent assessment groups to run some of that evidence generation there was a lot of variability in the quality and standards between different evidence groups. Often there are errors in those models and the reports generated. Subsequently, addenda must be issued. Sometimes one questions the assumptions that go into some of the models. We would welcome a broader debate about some of the assumptions that go into those models and the emphasis placed on the health economics and the concept of cost per QALY in the appraisal committee decision-making process.

Q607 Dr Naysmith: One of the things NICE may say in response is that often there are lots of mistakes, even arithmetical errors, in the submissions made to it by drug firms. Is it not a fact that in this area some mistakes are made? You still have not given me any examples of what you mean.

Dr Hasan: I can give you the example of the Alzheimer's disease appraisal. One assumption was that 30% of the costs of institutionalisation was not borne by the NHS. That may be based on some evidence that perhaps is not as current as we would expect. We know that some of the costs put into the economic models were perhaps a little out of date. Where one has the opportunity to have those discussions one can identify some differences between what maybe we would put into a model versus what one of the assessment groups would do.

Q608 Dr Naysmith: You argue that the conflicts between yourselves and NICE might be reduced if there was a clear rationale for how NICE reached its decisions if it was provided regularly. How much explanation do you believe is given at the moment either in private or public, and how would you like to see it made more explicit?

Dr Hasan: We would like to see some form of debate around how important the health economics are in the decision-making. We see an over-reliance on cost per QALY. I know that Professor Stirling Bryan has presented himself before the Committee. Only last year he published some research he had done into the NICE decision-making process. I almost reiterate some of the evidence you heard earlier today. There was a feeling among clinical experts and patient representatives on the NICE committee that they were sometimes out of their depth when there was a discussion about health economics. There was one quote in one of the papers about some of the clinical experts. You can see the way they are thinking. They start with the cost per QALY and then work backwards. The question we ask is: is that the right way to make a full and broad assessment of the clinical benefits of a particular technology that is delivered as well as the patient experience? Another example is Professor Anthony Goldstone who presented himself at one of the NICE appeals. Subsequently he wrote a letter to The Times in which he said he felt put down, that his opinions were not heard and that 30 years' experience treating cancer patients was largely ignored. He believed that decisions were being made by people who had never seen a case in their lives. We believe that there is much scope for improvement in terms of a broader debate on the real decisions that are being driven within that process. How much weight is being given to health economics? Surely, there must be some weight attached to that, but what weight is being given to clinical and patient experience?

Q609 Dr Taylor: Therefore, you agree with the previous witnesses that the right experts are not necessarily used by NICE?

Dr Hasan: Absolutely. One other point that is highlighted is: have they had the right training in health economics to be able actively to debate it?

Q610 Dr Taylor: Last week some of our expert witnesses criticised the quality of data that some pharmaceutical companies passed on to NICE: it could be incomplete, partisan or of poor quality. What is your response to that? Is that fair, or do you believe that the information you pass on is always absolutely superb?

Dr Hasan: I can speak only on behalf of Novartis. We believe that our submissions are of very high quality and we have a track record to demonstrate that.

Q611 Dr Taylor: Would it make a difference to pharmaceutical companies, not necessarily your company, if the eventual price of drugs reflected the quality of the evidence given?

Dr Hasan: We are certainly strong believers that the price should be reflected in the value that a particular medicine delivers. We believe that through these types of appraisal processes we are able to demonstrate the value of our medicines.

Q612 Dr Taylor: NICE seems to be more influenced by quantity rather than quality of life. Mr Winyard, do you think NICE has underestimated quality issues particularly for people who are at risk of losing their sight?

Mr Winyard: Without a doubt. I am not an expert on QALYs and health economics, but the system does have a bias towards quantity of life rather than quality issues. In the two appraisals in which we have been involved what has been frustrating is that they have been some of the longest in the history of NICE and each time NICE has first come out with its consultation document it has got it disastrously wrong. In the first case, in relation to PDT we would have gone to appeal but NICE withdrew the ACD because there was such an enormous outcry over a policy that said a person had to go blind in one eye before he or she could be considered for treatment. We went into the process this time for the anti-VEGF treatments full of hope. What happens? It does exactly the same thing. Of course, there is an enormous outcry. No one supports this; it is wrong and against good clinical practice. You will not find a single ophthalmologist who says that you should first let the patient lose sight in one eye. If you let that happen you do not know whether or not you can save sight in the second eye. NICE has got it disastrously wrong. The only thing the appraisal committee seems to be interested in is cost per QALY. It says in the literature that it is interested in the impact of the condition on people's lives; it wants to know what it is like to be blind. What would be the impact on the quality of life if one could keep one's sight? We present that evidence and there is absolutely no indication that it has been taken into account in any way. It is frustrating. Inevitably, that leads us to reflect the anger and frustration of our members and the wider society and then it is a very high profile public debate which is not ideal. I can see problems with that.

Q613 Dr Taylor: Does industry provide evidence on quality of life issues, or is that outside your remit?

Dr Hasan: We submit an economic case for all our medicines that captures the quality of life benefits, as well as the quantitative benefits, of those technologies, so we submit a cost per QALY model based on the evidence generated in our randomised controlled trials.

Q614 Dr Taylor: Is there hard evidence that elderly people, for example, value quality rather than length of survival?

Dr Hasan: As part of the process of generating that evidence often we undertake the right type of research to elicit what is called utilities, that is, a quality of life measure. NICE's own reference case suggests that that is done with members of the public. Therefore, members of the public are asked to quantify how much they value sight versus other things. That will capture those quality of life benefits. One point I should like to pick up from the RNIB is that if, for example, NICE's final decision is that an individual should be treated only for the better seeing eye, has it captured the impact on that patient having to be told by his or her doctor that treatment cannot be offered and the patient must return when the other eye is affected by the disease? What about the detrimental impact that has on the quality of life of that patient? These are the types of debates that we believe should take place at the appraisal committee so that there is a broadly informed understanding of how a decision is reached.

Q615 Dr Taylor: It is fearfully difficult, is it not? Do you believe that NICE takes any account of non-health costs?

Dr Hasan: Part of its remit is to focus very much on NHS costs only. Wet AMD and blindness is a very good case in point in that there are broader societal costs that should be taken into account. The challenge that we always get back from Sir Michael Rawlins is that he needs almost statutory permission to be able to go down that road and capture the broader costs. We know that in Sweden, for example, the LFN, which is almost equivalent to NICE, does capture broader societal costs. It does an economic evaluation taking into account benefits in terms of getting people back to work and off benefits. We believe that that is an area where that debate should be included.

Mr Winyard: There are two recent cross-national studies of the impact of sight loss and AMD on quality of life: one by Giselle Lebraune who led the team and a more recent one by Frank Holtz, a German ophthalmologist. Both demonstrate the major impact of AMD and sight loss of quality of life. As to the whole professionalisation of the assessment process, there does not appear to be an acceptance that QALYs are not scientific. There is a claim that they are scientific, but clearly they embody value judgments to a very great extent. Whom do you ask? You want to measure the importance of sight to quality of life. Does one ask the sighted public, or people who are in the process of losing their sight, or do you ask those who lost their sight five years ago, for example? You will get different answers from those different groups. Which questions does one ask? Does one use a generic questionnaire, the EQ-5D which is very limited, or something much more specific to AMD like the MACD QAL that has been developed by Professor Claire Bradley at London University which captures much better the full impact of AMD? If one goes in the direction of specific measures it becomes much harder to compare different disease areas. Basically, there needs to be a recognition that QALYs are not scientific and lead the whole assessment process in the direction of great complexity, and it is excluding. This week we have sat down with the Royal College of Ophthalmologists to look at the additional data provided by NICE following the very negative response to the appraisal consultation document. Clinical experts - the leading retinal specialists - and the patient group cannot understand it. We cannot make sense of the data that has been provided because it is in a very special language. One probably needs a master's degree in health economics before one can begin to make sense of it. It cannot be right that it is such an excluding process.

Q616 Dr Taylor: Do you have any suggestions for an alternative?

Mr Winyard: In a sense, it is there already. In the secretary of state's directions to NICE it is pretty clear that wider things should be taken into account: the broad balance of benefit and cost and the degree of clinical need of patients. If the appraisal committee can take rather better account of those things QALYs will be part of that process, but there is a wider picture and in the end you have to make some tough decisions. Is sight important? Everything tells me that it is. Your constituents will tell you that it is terribly important, and that must be captured.

Q617 Dr Taylor: How do you balance it against survival of an extra few months with a cancer drug?

Mr Winyard: I am not an expert on running health systems. I agree that that is a problem. Obviously, in one part of America the public has been asked about pretty well every sort of treatment and ranked them. Fortunately, that is not my problem. You need a system that recognises that there is no science that will deliver precise answers to these questions. One needs to take account of QALYs but in the end one must recognise what is important and what is less important.

Dr Hasan: I think there needs to be recognition that the QALY is an estimate. With most things there are wide confidence intervals around that estimate, but added to that it is almost a prediction. We are doing economic modelling sometimes with time horizons of 30 or 40 years. We are saying that what we know today will be replicated in 40 years' time. We also know that there are slight changes in assumptions which may be based on differences in clinical opinion. Therefore, one group of experts will say that a particular assumption is correct but another may have a completely opposite opinion. That can change the cost per QALY significantly. It could take it above the perceived threshold or even down to a negative value, ie that product dominates other products. There should be recognition of the strengths and weaknesses of QALYs. We suggest that part of the appraisal committee process is to say that in this disease area when assessing the health economic benefit, quality of life and cost per QALY these are the strengths of the assessment and these are the weaknesses. Let us have that debate and see whether we can come to some agreement.

Q618 Mr Scott: Do you believe that lower drug prices can be the answer to this problem?

Dr Hasan: I think we need more clarify as to the cost per QALY versus the price of the drug. You can have a very cheap drug that may not be very effective but has a very high cost per QALY because it is driven by the effectiveness of the product, whereas you may have what you perceive to be a high priced product that delivers significant benefit. An example, which I am happy to discuss, is that the SMC has already appraised Lucentis and in one scenario within the economic modelling the cost per QALY of that drug versus Visudyne being used with photodynamic therapy is about ₤5,000 per QALY. Therefore, at face value one may say it is a high priced product but when the economic modelling is done one sees that it delivers a significant amount of value and is seen as very cost-effective. On that basis it was approved by the SMC in June.

Q619 Mr Scott: Would not another option be a high quality product but a slightly lower profit margin?

Dr Hasan: One can debate profit margins versus price but that is probably a slightly different discussion. If one asks how to quantify that value one can use things like cost per QALY to show that a lot of products represent good value for money for the NHS.

Q620 Mr Scott: The obvious optimal option is to make sure that people do not have to go blind in one eye before receiving the drug. That may require give and take on all sides?

Dr Hasan: Absolutely.

Mr Winyard: I do not think RNIB has a view on drug pricing policy; it is way out of our area.

Q621 Dr Naysmith: We have looked at a number of systems in different countries. Some allow discussion about price whilst the evaluation is going on. That does not happen under current NICE guidelines. I know that you do not speak for the whole of the drug industry, but does Novartis prefer that kind of system?

Dr Hasan: There are strengths and weaknesses in every system. Clearly, the systems in France, Germany, Spain and Italy are very different, but, to give you a little insight, for Lucentis it is pretty uniform across the whole of Europe. For example, in France and Germany patients do not face the same barriers to uptake that we see in the UK. They see the value that the product delivers and they are happy to reimburse it at that price. When we take those sorts of pricing decisions clearly we need to think about the investment in terms of research and development, but the value we deliver with that particular product is clearly a factor we take into account. If one looks at the price of Lucentis versus other cancer medicines, for example, it is very similar, but to restore somebody's sight is a significant benefit.

Q622 Chairman: My PCT pays for the treatment of wet AMD with Lucentis. It also pays for Avastin which is not licensed for this treatment, but if the consultant and patient agree that can go ahead. I am led to believe that it is enormously cheaper than Lucentis. Notwithstanding that you have a vested interest in the drug produced by your company, that gives us a dilemma. I know of an individual who is receiving treatment with Avastin which is successful and has been having injections every few weeks. This week that patient has been told that no more injections are needed. It is believed that eyesight has improved since the patient has been on Avastin. Clearly, that is more affordable for my PCT which has many other calls on its budget; the drug is more affordable than Lucentis. How do we as taxpayers take a steer on this? Mr Winyard must debate this in the RNIB every day, because if it comes down to money that issue is out there at the moment.

Mr Winyard: It is a debate. As I said in my introductory remarks, we very much follow the lead of the Royal College of Ophthalmologists which broadly is that clinicians and sometimes individual patients on the basis of informed consent regard Avastin as the solution and so that is what those patients receive. The royal college also says that the quality of data available for Avastin is not the same quality as it is for Lucentis and therefore it does not recommend an Avastin-only service. It does not want to see primary care trusts simply running an Avastin-only service.

Q623 Chairman: It is a very difficult question for the taxpayer. Nobody wants to get this licensed and therefore it will not be at a competitive level with Lucentis. Everybody accepts, however, that it is less expensive than Lucentis. It seems to me that in those circumstances there is a real dilemma. Why is not somebody going ahead with it? It is quite right to say that in this country there is no comparable data because none has been collected and nobody wants to get it licensed for that particular form of treatment. Data has to be collected for that purpose. I understand that in America it is the drug of choice for the treatment of wet AMD. I do not know whether or not that is true.

Dr Hasan: We would challenge that assertion.

Q624 Chairman: But these are the matters that come across our radar in relation to these issues. There are real dilemmas in treatment. I am on your side, in that I believe that what NICE says about the treatment of wet AMD is illogical. That does not mean we should not question the cost to the taxpayer.

Dr Hasan: Our position is that Avastin has not been designed, manufactured or approved for use in wet AMD.

Q625 Chairman: In the UK?

Dr Hasan: Anywhere in the world. Being a physician myself, for the past 15 years the whole medical profession has been concerned about evidence-based medicine and the need to provide the evidence - randomised controlled trials, the robust gold standard of data - to prove that the product works. That is what the Medicines and Healthcare Products Regulatory Agency is about; it is there to safeguard public safety and assess evidence. Our position has always been: if you provide high quality evidence for Avastin we are happy to consider it.

Q626 Dr Naysmith: There are quite a few medicines in use that were not designed for the purpose for which they are currently used, and you must know many examples.

Dr Hasan: I accept that, but as a physician I would use those types of medicines in a situation where I had no licensed alternative. For example, most medicines in children are used off label, but there is no evidence or licensed product to say that that could be used as a preference, whereas clearly in this scenario there are products that have undergone rigorous randomised clinical trials involving thousands of patients to prove the benefit and safety of injecting such a product in the eye. However, in the case of Avastin we just do not know the risks. There are lots of uncertainties and unknowns.

Mr Winyard: RNIB is on record as saying that it wants a trial to take place. We support the IVAN trial and want to see it move ahead quickly. Similarly, in the States there will be a trial. If the data that comes forward shows that Avastin is safe and effective that is wonderful; it will be a much cheaper product and more people can be treated.

Q627 Chairman: Quite clearly, it will not interact in the way this particular drug does in terms of QALYs in relation to NICE. That is one of the issues that we are looking at. Mr Winyard, you said earlier - I should like you to confirm it - that having to wait to go blind in one eye is a major risk. The likelihood is that the eyes would not react in the same way to this type of treatment and one could lose sight in the eye that would react to Lucentis in a positive way. Is that clinically sound?

Dr Hasan: Absolutely.

Q628 Chairman: What we hear NICE is likely to do is completely illogical in those circumstances.

Mr Winyard: That is right.

Q629 Chairman: We can all make guesses at what the wider test would be. As somebody who is only slightly visually impaired, I just cannot comprehend how blindness would affect my life. I suspect that that applies to many of us. If we look at QALYs, do you believe there is any treatment that the visually impaired get on the National Health Service that could be or should be foregone so people can get comprehensive treatment for wet AMD? You said that it was a tough decision. This morning there was a bit of an academic discussion about a drug that prolonged life for a month. It is the easiest thing in the world for us to turn round and say we do not believe x thousands of pounds for another month is worth it, but we are not the patient, or the patient is not sitting in front of us. Do you think there is anything that the RNIB may be prepared to forego in terms of the treatment for the visually impaired under the NHS so that we have this comprehensive treatment?

Mr Winyard: Sadly, the level of provision particularly with low vision aids and support is poor and patchy, so there is not a big pot of money sitting there. This is another area where we campaign hard to try to get access to treatment in the 21^st century. If one loses one's sight maybe one gets a white cane, a magnifier if one still has some useful sight, perhaps a liquid level indicator and that is it. The whole of the government community equipment programme is moving away from the provision of services. Ideally, what people get in many cases is a CCTV which is enormously helpful in terms of access and information. At the moment, sadly if one loses one's sight the support one gets is very limited. In some places one must even buy the white cane. It comes as an incredible shock to the public that that is the case. The data that has emerged today from the Healthcare Commission suggests that maybe one quarter of trusts are not managing their finances very well, so there are other areas and procedures that in the end may be less important.

Q630 Chairman: Dr Hasan, do you think there are any areas in which your company should disinvest?

Dr Hasan: If you ask what proportion of the total NHS budget is represented by pharmaceutical products it is relatively small; it is about 11%. One asks about the other 89%. We always hear that QALYs are such a great measure because you can assess different types of technologies and interventions. We heard this morning about the cost per QALY of an exceptional case committee. Surely, we should be assessing the cost-effectiveness of that other 89%. What about building that new hospital wing or putting in place a new clinic? What is the cost-effectiveness relative to another intervention? We welcome that type of work. Let us have a broader debate. It is very easy to target pharmaceuticals because they are relatively transparent. Let us also assess the cost-effectiveness of some of these infrastructure investments.

Q631 Chairman: We are individuals and all react differently. There are bathroom cabinets up and down the land which contain hundreds of millions of pounds worth of pharmaceuticals that are never used.

Dr Hasan: Absolutely.

Q632 Chairman: You would be happy if we disinvested in that. It might cost your company some income if that was done.

Dr Hasan: If you said to me, "Here is one of your products where the data is weak. We think we should disinvest", I would ask to see the data. Over the past 12 to 18 months there has been a drive for NICE to provide guidance in terms of areas of disinvestment and there will be products or types of interventions where the evidence is not strong enough.

Q633 Chairman: What about tighter prescribing? I do not refer to your company. I have been in this place for a long time. I remember that in the 1980s when there was a central drive to restrict what drugs could be given to individuals a lot of noise was made by the pharmaceutical companies. They said that that was the wrong thing to do, and yet some drugs are prescribed which do not work in particular patients. Do you think that is an area that we should look at?

Dr Hasan: I think that is a question you should ask the BMA. A lot of physicians feel that they should have autonomy to choose the right drug for their patients.

Q634 Chairman: But that is a different issue, is it not? Some pharmaceutical companies may have better knowledge of what works in what individuals.

Dr Hasan: One area that is generating greater interest is the almost personalised approach to medicine. There may be interventions that do not work for the broader population, or maybe not as effectively, but everybody is interested in whether there are sub-populations of patients in whom we can see greater effect and consequently a greater degree of cost-effectiveness. That is the way medicine is going.

Q635 Chairman: I am tempted to ask you whether or not you would be prepared to look at this treatment on the basis that it will be paid for where it is successful.

Dr Hasan: The clinical trials show that over 90% of patients experience an improvement or maintenance in vision, so the drug is pretty effective.

Q636 Chairman: Would you want a system like that employed by the Scottish Medicines Consortium?

Dr Hasan: SMC and NICE were set up with slightly different remits and they serve slightly different healthcare systems in terms of the direction of travel. I believe that they have positive attributes and some weaknesses. In Scotland one has speed of guidance, which is a clear benefit. What we see now is that Lucentis is widely available in Scotland and patients are not being denied access to it, but there is less scope for consultation under that process. We welcome a debate as to how to improve the NICE process, and we believe there is opportunity in terms of transparency and collaboration. There are some methodological issues. There is also a question of driving implementation. We would encourage the Healthcare Commission to take very seriously the fact that PCTs may not be implementing NICE guidance.

Q637 Chairman: Has your company ever done any comparable studies and published them?

Dr Hasan: We look at how our products perform both with SMC and NICE. As you have heard this morning, there is a remarkable amount of consistency in terms of decision-making.

Q638 Chairman: If you have anything further that you can share with us we shall be interested in looking at it.

Dr Hasan: I will be happy to do so.

Mr Winyard: From our perspective, the two NICE appraisals in which we have been involved have been phenomenally slow, whereas in the case of the SMC we put in our evidence and three months later a positive result came out, which is great. It is very important that there is scope for some comment on draft proposals. The NICE process is wretchedly slow. If you ask about it, as I asked Andrew Dillon in Bournemouth, you do not get any clear answers. You are told that it is all to do with NICE being much more consultative and involving, but as consultees we are given a month to respond to the ACD. There is no flexibility for use. If we want to appeal we are given 15 days. There are periods of seven or eight months in the appraisal process when nothing appears to happen. It does not take seven or eight months to do a bit of economic analysis. There just is not the sense of urgency that needs to be injected into the system.

Chairman: Thank you for coming along. No doubt you will be looking at our deliberations with interest over the next few months before we publish our report on NICE and how it operates.