My Lords, I am very grateful for this opportunity to put some probing questions to the noble Earl, Lord Howe, and perhaps ask for his help with something that I am rather puzzled about. I detect a less than enthusiastic response from the medical and health establishment to the development and potential of what is being called the polypill. Perhaps the noble Earl will share the reasons for it and helpfully suggest a way forward for some more constructive engagement on the issue, if that is at all possible.
As we know, strokes and heart disease remain a major public health problem. Across the population as a whole, the chance of having a heart attack or cerebrovascular accident rises as people get older, and age is the single most important predictor of future cardiovascular disease. But we know now—there is robust evidence—that the consumption of fixed-dose polypills containing effective combinations of low-cost off-patent statins and blood pressure medicines can safely cut the rate of unwanted vascular events by 70% or more in otherwise untreated subjects, whatever the initial combined level of their blood cholesterol and other disease risk factors. The use of such a preventive technology across the general population, with access determined by age alone, would prevent the need for much more costly and inefficient risk-testing, and maximise the health gains. Clearly, it is aimed at people in their 50s and 60s who would not at the moment meet any treatment threshold.
The use of the polypill focuses on primary prevention, whereas the majority of current medical activity is focused on secondary prevention. Of course, if a first heart attack or stroke is prevented, there is no second one to prevent. My understanding is that if people take this daily from the age of 50, one in three people would benefit and would gain an extra eight years of life without heart attack or stroke—similar to the benefit achieved by stopping smoking in middle age.
I suppose that the polypill can be thought of as a form of drug-based vaccination that reduces vascular disease rates. However, unlike the situation with vaccines, there is no threshold level of use needed to ensure herd immunity—the higher proportion of healthy people taking the polypill, the greater the benefits—but no one needs to be encouraged against their personal judgment to take it if they do not wish to do so.
An article in the BMJ in April, which contained research news, said:
“Inconsistencies in the design of studies investigating the potential of polypills to prevent cardiovascular disease make the impact of these pills difficult to prove, a systematic review by the Cochrane Collaboration has found. However, the reviewers are confident that polypills do have a role in protecting large populations against cardiovascular disease”.
One would have thought that there would then be a great rush of enthusiasm by the NHS and indeed the medical and health sector generally to use the polypill. But as far as I can see, we have had mostly silence and in some cases downright hostility. There has clearly been difficulty making a polypill with a licence for the primary presentation of cardiovascular disease, and pharmaceutical companies see little commercial advantage because the components of the polypill are all generic. I understand that they are also put off by the uncertainty and cost of obtaining regulatory approval.
I wonder whether we are seeing here a parallel to the statin debate, which, as a lay person, I have found utterly confusing. I pick up the sense among some sections of the medical profession, particularly the public health profession—and I stand here as president of the Royal Society for Public Health—that pills are not really virtuous. It feels as though there is a puritanical approach which suggests that healthy living is the only appropriate policy to adopt in the prevention of stroke and heart disease. I also suspect that doctors fear the workload implication of this kind of medication when it comes out. Perhaps they also fear losing control. In a sense, the use of polypills could be seen as the public very much taking ownership of their own health.
There is no evidence that the use of polypills would lead to increased vascular disease risk-taking. I understand that the available studies imply that health-promoting behaviours tend to be positively correlated with one another, as might be the case with health-damaging behaviours. As with vaccines, the introduction of a general polypill prevention programme within the NHS would probably require a positive, proactive approach, possibly in the form of some government/private partnership.
I was interested in the Government’s approach to antibiotics last week. Clearly, the current mechanisms—the factors that lead pharmaceutical companies to make major investments—were simply not going to produce the goods and the Government felt that they had to step in. Will the Minister consider whether his department might at least play a somewhat more active role in this debate than it has done hitherto? Would he, at the very least, be prepared either to convene a study or an objective, independent review of the potential of the polypill? Would he, at the very least, be prepared to meet me and colleagues to discuss whether there is a way to take this forward?
I am puzzled that, on the face of it, the polypill could lead to a major reduction in the number of heart attacks and strokes that occur in this country, yet the combined efforts of the medical, health and pharmaceutical establishments seem to want to look the other way. Why?
My Lords, the name polypills is slightly unfortunate. When I heard about this, I immediately drew parallels with polyclinics, keeping it in the health arena, at least; but one of my adult children wondered whether this was veterinary medication for our avian friends. The principle, as the noble Lord, Lord Hunt, has outlined—I thank him very much for securing this debate—is that the polypill combines four medicines into one; three to lower blood pressure and one to lower cholesterol. Personally, I prefer the name that they have used in Australia and New Zealand, SPACE: single pill to avert cardiovascular events. It seems a neater acronym and explains much more simply what it does.
I thank the Library for its very helpful research pack, not least because it references the proposal that all over-50s should take it. This is some of the research referred to by the noble Lord, Lord Hunt. Some even suggest that those over 35 who have an at-risk profile might consider taking it every day. Indeed, Dr David Wald at Queen Mary University of London, after his trial, says that 28% of people will benefit by avoiding or delaying heart attacks. However the QMUL studies trial was only 84 patients; perhaps I should say “people”, since it was targeting people who were not yet unwell. Those results show that the blood pressure of around 12% of participants was reduced and 39% had reduction in cholesterol. All this is good, but to have a drug compulsory—because that is how it would be seen, even if it were voluntary—for anyone over 50 seems to me a fairly low benefit ratio.
The papers also describe a cost of “only 50p per day”. This sounds relatively cheap, but it is £15 per month or £180 per year. Even more than that, Dr Wald suggests that it could be sold over the counter and not as a prescription-only medicine. I do not know what the current rate is, but the per-patient allocation for medication in the NHS is not large, and anything over £100 starts to raise eyebrows. The pill would therefore be a substantial burden on the pharmaceutical bill, especially if it was to be used for the entire population over 50 rather than for those who need it.
Even if we accept that there is a good reason to give four tablets in one for healthy people, other considerations still need to be aired. The first is side-effects. The noble Lord, Lord Hunt, referred to statins —I suspect that we all know somebody who is on them—the side-effects of which can range from memory loss, muscle problems, polyneuropathy, acidosis, anaemia, cataracts, immune depression and pancreatic and liver disease. Even if you are lucky enough not to have a response to a single one of those drugs, mixtures of drugs may well have combination side-effects. I know from my own area of rheumatology that some people react badly when a mixture of drugs is taken, and they are instructed to take certain drugs in the morning and others in the evening to avoid such contraindications.
I am slightly unhappy about the reference made by the noble Lord, Lord Hunt, to the polypill being parallel to vaccination. I would much rather that people who were thought to be at risk, which could well be anyone over 50, went down the public health route and were asked to consider lifestyle changes, including stopping smoking, looking at their diet, having their cholesterol tested regularly and, most importantly, undertaking some activity. A lot of publicity was given two or three weeks ago to evidence showing that, for the population over 50, you do not have suddenly to become a Tour de France cyclist or a marathon runner and that steady walking that raises your exertion level a bit every day will do the trick.
I therefore wonder whether this “wonder drug” is not trying to solve too much in one easy go, but I am not alone. In an article that appeared in the Daily Telegraph on
“The history of medicine is rich with ideas that sounded great but either didn’t prove effective—or worse, did harm”.
Natasha Stewart, a senior cardiac nurse at the British Heart Foundation, was reported as saying:
“Research into polypills is encouraging, but there are still many questions to answer before this ‘wonder drug’ is prescribed … However interesting this potential new pill is, medicines are not a substitute for living a healthy lifestyle”.
The polypill sounds very enticing, but I am concerned about it for three reasons. First, it is already being described as a wonder drug long before extensive research and careful monitoring of side-effects, including those caused by combining four into one, have been done. As I said earlier, many people are already under strict instructions not to mix certain drugs because they interact. Secondly, the cost at 50 pence a day is not insignificant. To prescribe the pill for a large number of people who will not need it in the longer run seems futile. Like Public Health England, I would much rather see proper medical assessment MoTs being given at 35 and 50, so that people becoming more at risk can be given lifestyle change advice, have regular tests on cholesterol and other things that will indicate whether they are at risk, and can consider whether their level of activity is appropriate. My final concern is that, if the polypill is made available across the counter and not on prescription, some—perhaps many—may think that the pill alone will protect them without their looking at their own lifestyle issues.
Having been pretty depressing about all this, I want to end on a positive note. If further research at a statistically significant level can demonstrate the benefit of the pill, and if the Medicine and Healthcare products Regulatory Agency is satisfied with its efficacy, quality and safety, then, yes, I would welcome it, but there is too little for us to go out and be utterly positive about at the moment.
My Lords, I too am grateful to my noble friend Lord Hunt for introducing this debate. It is pretty obvious that he, like me, has been briefed by Sir Nick Wald—and I suspect that the noble Earl may have heard a little from him too—so if what I say sounds a little familiar, I hope he will forgive me. Heart attacks and strokes remain among the biggest killers, despite the improvements in mortality rates in recent years. We know many of the risk factors—smoking, alcohol, obesity, salt and lack of exercise—and we must not be distracted, as the noble Baroness, Lady Brinton, says, from dealing with these public health issues. They are not mutually exclusive, of course.
We know that we should do more to detect and treat high blood pressure and raised blood cholesterol levels, but there is one important risk factor that we can do little about. That is age. There is a straight-line relationship between age and the incidence of heart attacks and stroke. The older you are, the higher the risk. The most striking thing about this is that about half of those getting one of these killers do not have one or other of the conventional risk factors—they have normal cholesterol and normal blood pressure. They come as a surprise in people thought to be fit, and it is in these unsuspected and unsuspecting individuals where the polypill may play a role.
The rationale for the polypill relies on a number of basic principles and here I rely specifically on Sir Nick Wald’s briefing, so what I say, as I pointed out, may not be entirely novel. First, we know that using drugs to lower a raised serum LDL cholesterol reduces the rate of heart attacks, and lowering the raised blood pressure reduces the incidence of strokes, but the intriguing observation is that the same drugs reduce even normal levels of cholesterol or blood pressure to a similar proportion as in those with raised values.
Furthermore—and here is the nub of the argument—lowering even normal levels reduces the risk of heart attacks and stroke. For example, Nick Wald calculates that a fall in blood pressure of 10 millimetres of mercury reduces the risk of stroke by about 60% and reducing serum LDL by 1 millimole per litre lowers the risk of coronary artery disease by 40%. The fact is that there does not appear to be a lower limit below which reducing blood pressure or cholesterol is not effective in reducing risk.
The second principle is that you can achieve as good or better effect in reducing blood pressure from a combination of two or more hypotensive drugs given in half or lower doses than a single drug given in a normal dose, and in this way markedly reduce the incidence of side effects. You get the same impact on blood pressure with many fewer side effects from a combination of half doses.
Therefore, combining these pieces of evidence—risk increasing with age, lowering risk factors even when they are seemingly in the normal range, and combining low doses of drugs to reduce side effects—leads to a conclusion that points to a need to give polypills as a preventive measure to those at risk, namely all the population over the age of 55, say, regardless of their conventional risk profile. Indeed, if they have other more obvious risk factors they are likely to be treated for them by one means or another already. It is the unsuspecting population where a polypill is most likely to be effective. In these, it lowers cholesterol and blood pressure as well as risk.
Nick Wald has suggested that one in three individuals taking a polypill containing small doses of simvastatin, losartan, amlodipine and hydrochlorothiazide would live an extra eight years than they would have done without the pill. It could reasonably be concluded that we should be giving everyone over 55 a polypill of this type, and it would help those harbouring unsuspected coronary artery disease or strokes. If this were a preventive programme like vaccination, as my noble friend suggested, we probably would not hesitate, but of course it is not a one-off, single shot like a vaccine. It is to be taken life long, every day, as a prophylactic treatment, more like the contraceptive pill to prevent pregnancy, although of course for rather longer.
So many issues would have to be overcome, and a number of critics of the mass medication that such a programme would entail have to be answered. There is the question of regulation. Although all the constituents of the pill have been through all the regulators and are in fact well out of patent, the MHRA and MEA may well need convincing that the combinations do not need further appraisal and approval. There is the question of side-effects. Although doses are low, there are undoubted side-effects with all the constituents of the pill, even in the low doses used here. They may well become significant when trying to reach whole populations.
Some say that we are already an overmedicalised society and we do not need yet more pills for everyone. I am not sure that that is a terribly good argument, because we rely quite heavily for our longevity on many of the medicines we take. I am one of the few, it seems, who is on simvastatin without side-effects, out of a huge population who are similar to me. In any case, no one is forced to take drugs if they do not want to. Nevertheless, those are views that we cannot easily dismiss and to be taken seriously.
We come to the question of whether the polypill should be available for prescription on the NHS or simply over the counter at pharmacists. It is probably very cheap, and the economic value of preventing those diseases is a strong argument for prescription. It would at least allow us to get a clear angle on the number and incidence of side-effects, which free availability would not. It would allow doctors the opportunity to assess their patients for other preventable risk factors at the same time, which we have to do something about. On the other hand, an approach in which people simply decide whether to buy the pill over the counter is certainly more libertarian, but would probably not make a great impact on the epidemiology of those diseases, nor on the health of the nation.
There are certainly interesting debates to be had, and I am very grateful to the noble Lord, Lord Hunt, for starting us off on this topic.
I am grateful to the noble Lord for giving way. One issue raised earlier was about the dosage and combining those dosages in relation to particular side-effects. It was only 12 months ago, I think, that NICE advised against giving particular doses of simvastatin together with a modifier. When doses are given separately, you can take the evidence and change them. When they are combined in a polypill, that goes out of the window and you are left with all the elements at the dosages that have been agreed. Is that not an argument for retaining the current position of giving separate dosages rather than combining them all?
Those are very good points. The doses used in polypills are very low, in fact—20 milligrams of simvastatin, when the normal dose is 40 to 80 milligrams. The other drugs in the polypill are half doses. The point is that, if you have raised LDL cholesterol or raised blood pressure, you should certainly be on the treatments; they have been shown to be effective. It is people who do not have raised cholesterol or raised blood pressure who we are aiming to treat—or to prevent their diseases—so it is a different situation. The point about safety is important. It is clear that we need and should have proper clinical trials of those doses, but the impact of such doses, from what we know about them in this combination, is that they are likely to be safe in the vast majority of cases. What we do not know is the number who will get side-effects.
My noble friend, and other noble Lords, mentioned the importance of clinical trials, which I am sure is absolutely right. Is not the problem here that in fact no pharmaceutical company will conduct a clinical trial because all the drugs used in combination in the polypill are off-patent, so there can be no protection of that research by any company taking it forward? So there is, if you like, a block here, although people can see the potential benefits. Rightly, noble Lords are asking for clinical research, but there is no possibility of that happening unless the Government take a hand themselves, which is why the debate on antibiotics is interesting. They are completely separate subjects, but the Government had to step in there because, at the moment, the market simply cannot respond to the issue.
I agree entirely. I think that it will be difficult for the drug firms themselves to conduct trials because these are generics and they are manufactured by a number of companies. The only way forward, I suspect, if we are to have a clinical trial, is through NHS funding—that sort of trial. My final remark is that I very much look forward to the noble Earl’s response.
My Lords, perhaps I might say a few words since we have a little time in hand. I am very interested in the points raised by the noble Lord, Lord Hunt, because preventing cardiac disease is something that we should be considering for the future. Indeed, I think we are all agreed on that. However, I can see many of the problems. I very much agree with the noble Baroness, Lady Brinton, that we have to be careful that people, especially young people, do not think that this is a sort of panacea—especially with obesity and the danger of diabetes, for example—and that by taking this magic pill we will somehow put off the moment. That would be dangerous. However, I can see that with more research—this is where I agree absolutely with the noble Baroness—this is something that we should keep an eye on. I am very grateful for the debate, which I found extremely interesting.
My Lords, perhaps in the time we have I might make a very short intervention because I agree with my noble friend in her analysis. I feel that there is a real issue not simply with the polypill but with the research, which needs to take place where there are combinations of drugs being given anyhow. You can give a combination of drugs without having serious clinical research and that is okay, but if you combine them into a single dose, you need a complete clinical trial. That issue has to be addressed.
My Lords, I thank the noble Lord, Lord Hunt, for giving us the opportunity to debate a particularly interesting subject and for having elicited a number of very well informed speeches. In calling for this debate, he has done the House a considerable service by enabling noble Lords, including myself, to bring ourselves up to date on what progress has been made in the development of the polypill concept. As has been said, heart attacks and strokes are major health issues in the western world and a growing issue in the developing world. Reducing mortality for people with cardiovascular disease and improving their outcomes is a key priority for the Government. We have made it clear, through the NHS and public health outcome frameworks and the Government’s mandate to NHS England, that we want to see action taken across the health system to reduce avoidable premature mortality from cardiovascular disease.
The 2013 call to action on premature mortality set out the Government’s ambition for England to be among the best in Europe in tackling the leading causes of early death, including cardiovascular disease. In April this year, we published Living Well for Longer, which brings together what the health and care system will do to meet this challenge.
There has been a great deal of interest in the polypill and its potential for reducing the risk of heart disease over the years. It may surprise some noble Lords that the concept was first introduced into the scientific and public domain as far back as 2003. It was proposed in an article in the British Medical Journal by two people whose names have been mentioned already, Professors Nicholas Wald and Malcolm Law of the Wolfson Institute of Preventive Medicine. Using mathematical modelling, they estimated that a polypill comprising a statin, aspirin, a combination of three blood pressure lowering drugs and folic acid, could reduce heart disease events by 88% and stroke by 80%. Their article concluded that their proposed polypill could,
“largely prevent heart attacks and stroke if taken by everyone aged 55 and older and everyone with existing cardiovascular disease.”
Although the effectiveness of the combined drug and any possible side-effects had yet to be evidenced though patient trials, this captured the imagination of the public health research community, particularly for the prevention of non-communicable diseases such as cardiovascular disease.
Essentially, the polypill is a combination of multiple medicines which aims to prevent or reduce the risk of cardiovascular disease: that is, strokes and heart attacks. Each of the constituent medicines is either at the current recommended dose or at lower doses. The premise is that these combinations should be used in preference to using the same medicines separately. In practice, the polypill can refer to either the fixed-dose combination medicine to reduce cardiovascular risk, patented as the polypill, or any other fixed-dose combination medicine, such as the red heart pill. However, any discussion of polypills is complicated by the huge range of drugs which might be included in any combination.
Polypill active ingredients are licensed separately as medicines and well established in their own right; their use together in fixed combination is what is novel. Just like any other medicine, any application for a marketing authorisation for a polypill needs to be supported by data demonstrating that its quality, safety and efficacy are satisfactory and that the risk-to-benefit profile is favourable for the proposed treatment before such an authorisation or licence can be granted.
My noble friend Lady Brinton drew attention to the side-effects of polypills and statins. She was absolutely right to do so. My information is that the evidence is not yet there on the side-effects of the polypill. Patient safety must of course be paramount in that context.
No polypills are currently licensed for use in the UK for the prevention of heart attack or stroke. I understand that the Medicines and Healthcare products Regulatory Agency has provided scientific advice to a number of sponsors and companies for combination products of this type. However, no application has yet been made to the licensing authorities. In the event that a marketing authorisation proposal is submitted, the data supporting any claims for benefit in the stated patient population, together with any evidence of adverse events, will be carefully reviewed. Only if the overall balance of benefits versus risks is favourable will a marketing authorisation be granted.
Without a marketing authorisation, as the noble Lord will know, doctors can prescribe an unlicensed medicine under their own professional responsibility. That addresses one question raised by the noble Lord, Lord Turnberg, as to whether it is in theory available on the NHS. The answer would be yes, in those circumstances, but any national action to promote the use of a drug that is not licensed is out of the question, as I am sure he is aware. I understand that there are several clinical trials of polypill products in progress in various countries and it will be interesting to see the results.
The noble Lord, Lord Hunt, questioned whether it was the fear of additional workload that was deterring doctors in the context of the polypill. My information is that the evidence on that front is as yet unavailable one way or the other, as regards the primary prevention setting, but that clinical studies are now under way. Indeed, I have in front of me the details of three polypill phase 3 clinical trials which had either completed or were close to completion as of May 2014. I can let the noble Lord have details of those trials if he would like me to do so.
The noble Lord, Lord Turnberg, raised the possibility that the polypill could be prescribed to those people who do not fall into the risk group. That is, of course, the primary prevention group. I am advised, though, that as age advances, the risk of side effects also increases proportionally. I suggest that before embarking on a course of this nature, we would need evidence that the polypill influences benefit more than risk. We therefore come back to the issue of clinical trials in order to demonstrate that.
Having said that, to answer another of the noble Lord’s questions, I accept that the polypill could be more convenient for some patients and could help them to adhere to their medicines. Whether it would prove cost-effective is something that NICE might in due course consider.
I know that not everyone is convinced by the polypill. There are, for instance, concerns about the medicalisation of otherwise healthy people. Even by its proponents it is seen as secondary to other forms of prevention. Professor Wald himself is quoted as saying:
“This is not the solution for primary prevention … Primary prevention requires education of the public. As a priority this is much more important than any polypill”.
There is a range of population-based interventions that could be put in place to reduce the risk of cardiovascular disease. Each has its pros and cons and may be suitable for some patients and in different circumstances. We know that many premature deaths and illnesses could be avoided by improving lifestyles. The Government’s public health programme includes national ambitions to reduce smoking, obesity, physical inactivity and the harmful use of alcohol—all with appropriate metrics included in the public health outcomes framework.
In addition, through the NHS Health Check programme people between the ages of 40 and 74 are offered a range of tests that include measuring their cholesterol and blood pressure levels. The check has been designed primarily to help healthcare professionals identify cardiovascular risk in the adult population earlier so that steps can be taken to reduce it, but it is worth emphasising that it is also targeted at a range of other conditions.
All 152 local authorities are now offering the NHS Health Check programme, which is a significant milestone in the programme’s evolution. In 2013-14 a total of 2.8 million people—almost 20% of the eligible population—were offered an NHS health check, and just over 1.4 million of them received one, giving a take-up rate of 50%. This is the greatest number of NHS health checks offered and accepted in one year since the programme began.
That is all extremely credible. However, the polypill is aimed at those who have passed the health check with flying colours—that is, they have normal cholesterol and blood pressure, do not smoke and are not overweight. It is with this group of individuals, who are not suspected of having the liability to develop a heart attack or stroke, where it seems to have its place.
Again, that is the primary prevention group, and the point that I was seeking to convey earlier was that we would need evidence that the benefit-to-risk ratio was sufficiently positive before proceeding down that course. That is not to say that it is not, but there is work to be done to prove it.
In March 2013 the Cardiovascular Disease Outcomes Strategy was published. This set out possible actions within the current legislative framework, systems architecture and financial settlement to deliver improved outcomes for people with CVD. It set out a framework for 10 actions that would make a real difference in improving outcomes for patients and their families. While I could expatiate on that subject, I am told that my time is drawing to a close, so suffice it to say that I hope that noble Lords have found today’s debate as interesting as I have.
The polypill is certainly an interesting concept. It may be that this type of approach would be more suitable in developing countries, where the real epidemics of cardiovascular disease are building up and where clinical trials are taking place, rather than in a more sophisticated healthcare system such as ours, where prevention and tailored therapy are more the norm. Time will tell.
On the issue of market failure, which was introduced by the noble Lord, Lord Hunt, I am not convinced that the same arguments apply to the polypill as apply to antimicrobials. For one thing, there are a number of clinical trials of polypills in progress, as I mentioned, and the MHRA has provided scientific advice to a number of companies, so clearly there is commercial interest out there. We do, however, welcome any technologies that contribute to providing the best treatment for people with cardiovascular disease.
In answer to the main question of the noble Lord, Lord Hunt, of whether the Government will consider playing a more active role in this debate, I would certainly be interested in looking at the noble Lord’s proposals in more detail and would be happy to discuss the matter with him at a suitable moment. With that, I thank him once again for introducing this extremely interesting topic for our consideration.