The Bizarre, Unpredictable and Shameful World of Drug Pricing

In recent months I have become so used to being bashed over the head by press releases from the Department of Health, that I have developed an almost Pavlovian response – the head bows, the shoulders go down, I duck for cover.

So it was only while peering carefully from a place of safety that I was pleasantly surprised by one of their latest pronouncements – to give NICE new responsibilities to look at fair pricing for pharmaceuticals.  For all its imperfections, NICE has been one of the best developments in the NHS in recent years. It has brought some much-needed clarity to prescribing guidelines and a degree of protection from the seemingly irresistible lure of the latest best thing to be marketed by the pharmaceutical industry. It can only be a good thing for NICE to be more involved in helping to bring common sense, and the needs of the NHS, to bear upon drug pricing.

In fact, I think it is such a good idea, that I would like to make some suggestions for how they could take things even further – by looking at some of the bizarre, irrational and often downright scandalous anomalies that exist within the drug tariff.

Take nebivolol, for instance, an important beta-blocker for some cardiac patients. It comes in both 2.5mg and 5mg tablets – how can it possibly make sense that the half-strength tablet costs the NHS over 30 times as much as its stronger counterpart? The anti-depressant paroxetine is similar – the multiplication factor is less extreme, with the 10mg tablet being only 6 times more expensive than its 20mg cousin, but the illogicality and blatant unfairness is the same.

Lest any doctor get wise to the fact that lower strength tablets might be more expensive, we have the opposite situation with omeprazole. For most drugs it is more expensive to prescribe two low dose tablets than a single tablet of a higher dose, but 40mg omeprazole is twice as expensive as the equivalent dose in 20mg tablets. I have to ask my patients to swallow their pills twice as often, but most are more than willing once they realise it is the scarce resources of the NHS which are at stake.

Even if I prescribe the drug perfectly, price inflation can still happen in the most unpredictable way before the medicine leaves the pharmacy. The breast cancer drug letrozole is a prime example. It is only given as a 2.5mg dose, so what could possibly go wrong? Well, it turns out that pack sizes can make all the difference. If the drug is issued in packs of 14 the price is £1.89, while packs of 28 cost a staggering £73.24. What is going on here? A pharmacist who is on the ball and gives 2 packs of 14 will be saving the NHS nearly £70 a time – but if they all did that then how come the packs of 28 would manage to sell?

How am I meant to know all of this? Can I remember it all, each and every time I prescribe? Even if I could – do we want doctors to have to learn the prices of drugs? Wouldn’t we rather they spent their time keeping up to date with real medicine instead?

There can only be one reason why these pricing anomalies occur – bombard and bamboozle doctors enough with confusing prices and some of them won’t notice, leading to vast sums of money bleeding its way into the coffers of big pharma. It is a marketing strategy that is not unfamiliar to anyone who pays a utility bill; price plans are so bewildering that the companies rely on many of us making the wrong choice and paying over the odds. The Government has become wise to this and is trying its best to limit the number of price plans companies can offer.  If the Government can protect the voting public in this way then it should do the same for the NHS and start limiting the marketing opportunities of the pharmaceutical industry.

NICE should be involved in changing this. I have a simple formula to suggest to them, and it goes like this: Every drug should have an agreed, fair price for its lowest dose, and as you double the dose, you double the price. What could be simpler? There would be no more bizarre pricing arrangements, nor could a drug rep boast that their product has a fixed pricing regime whilst their rival’s does not – nor could the tariff be changed at the whim of the company once my patients are established on their treatment.

Everyone would know where they were, every drug would be fair. Simples.

I am very grateful to our pharmacist at Binscombe, Rebecca Huish, for helping me research this post, which was originally published in Pulse magazine (access through free registration).

Whisper it: UK Cancer Care is Better Than We Think

The prevailing narrative surrounding cancer care in the UK is one of self-depreciation. Patients are assumed to be reticent about seeing their GP when they develop symptoms, either due to the stereotypical British stiff upper lip, or because the Great British Public is wallowing in such ignorance that it is in dire need of yet another awareness raising campaign. GPs are derided for being a barrier to referral, and are generally regarded as being in constant need of retraining. Even if you do recognise the symptoms and fight your way through the wilful ignorance of your GP, we are led to believe that the sole purpose of NICE is to deny you the life-saving treatment you would receive in any other developed nation. The end point is the recurring complaint that the UK ‘lags behind’ the rest of the world.

We are so used to hearing the negative voices that envelop UK cancer care that it can be rather startling to hear the occasional good news story that somehow slips through into the media. The recent report that GPs are actually really rather good at spotting cancer is a such an example. This national audit of cancer patients demonstrated that most patients presenting to their GP with symptoms of cancer are referred after only one visit – with a median referral time of zero days for these patients – meaning that they were referred on the day of presentation. Overall, more than 80% were referred within two consultations, and those that took longer tended to be cancers that were harder to spot in the first place. The lead author Georgios Lyratzopoulos said: “Much is assumed about GPs spotting cancer late, but these data show that in the great majority of cancers the suspicion is made promptly.”

The overall picture in cancer care is surprisingly positive also, with cancer death rates on the decline, and projected to continue to fall over the next two decades, and the World Health Organisation Cancer Mortality database places the UK comfortably in the middle of the table, just above Germany – maybe British patients aren’t so neglectful in their health-seeking behaviour after all.

Whenever the evidence points in a positive direction, the good news is frequently welcomed with an air of reluctance – you can almost hear the grinding of gritted teeth in the sound bites. Sara Hiom, early diagnosis director at Cancer Research UK, reacted to the audit on GP referrals with: ‘Progress is clearly being made, but one in five people have to make more than two visits to their GP,’ while the Department of Health responded to the excellent news about falling death rates with: ‘These figures reflect improvements in cancer services, but we know there is still more to do.’

Of course we should not be complacent, but the dominant perception that cancer care in the UK is somehow inferior to much of the developed world should worry us – because there are too many vested interests that depend on keeping up this bleak outlook. Politicians benefit, as they know that declaring: ‘We must do better,’ is always a vote winner; cancer charities are nervous about good news because their funding depends on their still being a job to do; while those right-wing commentators in search of a US-style health service will relish anything that allows them to bash the NHS.

This is no mere philosophical debate, but a key driver for major NHS policy – the NHS Mandate seeks to save lives by reducing mortality rates from cancer, but then demands an improvement in 1 and 5 years survival rates – the favoured statistic of those who seek to downplay UK performance and a dangerously unreliable method for comparing one country with another. If we allow this misdiagnosis of cancer care in the UK to continue, we will be vulnerable to accepting treatments we do not need – increased screening, over-diagnosis and over-treatment in particular – and all the associated harms of unnecessary intervention. It is time to stop whispering, time to stand up for the NHS, and say, loud and clear: ‘Actually, we do pretty well!’

This article was originally published in Pulse (access restricted to healthcare professionals).

Statins – Time to Change the One Size Fits All Approach

Let us assume for a moment that you have a spare £10 000 that you wish to invest. This is unlikely in these times of austerity, I grant you, but it would help if you could suspend your disbelief for just long enough to follow through the analogy. You decide to seek the advice of an esteemed independent financial advisor and present your happy situation to her. I suggest you would be somewhat startled if she took note of your age, gender and postcode, considered the size of your investment and then wordlessly consulted a set of tables compiled by the National Invest your Cash Emporium (NICE for short), nodded wisely and declared: “The guidelines recommend the Futures Market – copper in fact – sign here and it’s all done.”

Startled enough to take your money elsewhere, I suspect. Of course a good financial advisor would do no such thing. She would ask how you feel about investment and risk; is this really spare money and you could cope without if stocks went ‘down as well as up’; or is it your life savings that you just need to keep safe for a year or two before you splash it all on the holiday of a lifetime when you retire? In short, you would be at the centre of things, saying what is important to you, relying on the specialist knowledge of the expert, but taking charge of the decisions you make.

What happens, then, when you take the somewhat less desirable burden of cholesterol readings, blood pressure records and family history to the doctor, seeking to invest in your own future health? Well, the doctor will take note of your age, gender and postcode, consider the size of your cholesterol, blood pressure and cigarette packet, and then wordlessly consult a set of tables compiled by the National Institute for Clinical Evidence (NICE for short), nod wisely and declare: “The guidelines recommend a statin, here’s a prescription, you can pick it up next door.”

At least that’s the essence of what the NICE guidelines tell us to do. In reality a good GP will add a much more human touch than this, and try their hardest to incorporate the patient’s perspective, but this is more in spite of rather than because of the guidelines, and patients can all too easily feel like they are being railroaded into taking treatment they are not sure about.

The guidelines state that: “Statins are recommended…for adults who have a 20% or greater 10-year risk of developing cardiovascular disease.” Recommended is a strong word for both doctors and patients. For doctors it makes us feel we are negligent if we don’t prescribe, while patients are left to feel that in going against guidance they might be taking foolhardy risks with their health. There is some leeway in the NICE report – it states that the decision whether to prescribe or not should be taken: “After an informed discussion between the responsible clinician and the individual about the risks and benefits of statin treatment, and taking into account additional factors such as comorbidities and life expectancy.” – so there is some room to discuss risks and benefits, but the factors we should take into account are comorbidities (other health problems) and life expectancy – no mention of the patients feelings or preferences.

We are all wonderfully different with a richly diverse range of feelings and preferences. When it comes to financial investment some of us are happy to take big risks if there is a chance of real gain, taking a nothing ventured… approach to life. Others are more cautious and will always play safe, still others trust no-one and would rather invest in a burglar alarm and better locks while hiding their savings under the mattress. So too with health. For some, the risk of stroke is paramount and even a 10% risk over the next 10 years seems too high. If a tablet might reduce that risk then they’ll want to give it a try. Others are more cautious with tablets and hate the idea of being on them, they’ll take them if they have to, but would really rather not, while still others have a fatalistic view of life – if a stroke will happen then it will happen, just don’t bother me with pills. None of this is wrong, and is something to be celebrated rather than ignored and hidden away.

A study published in The Lancet hit the news last week with the suggestion that more healthy people should be prescribed statins for cholesterol, and there were calls for NICE to lower the guidance threshold from 20% down to 10%, but this misses the point – who are NICE to decide what sort of risk you are willing to take? There may be a risk below which the NHS is not willing to fund treatment, but other than this NICE should present the evidence in a way that enables doctors to help patients make informed choices about their treatment without pressure to conform or be a good citizen for the sake of population statistics.

Importantly, for an informed decision to be made, the statistics need to be meaningful – which means absolute risk reduction, not relative risk reduction. Newspaper headlines and enthusiasts love relative risk measurements – they are far more exciting – but sadly they are often highly misleading. For The Lancet study the relative risk reduction is the same whatever your actual risk of heart disease – for every 1.0mmol/l fall in cholesterol there was a reduction in the risk of heart disease of just over 20% for all categories of patient. Hence the headlines excitedly stating that healthy, low risk people stand to gain as much as those at high risk. The trouble is that a 20% reduction in a small risk does not amount to much. If your risk of heart disease in the next 10 years is 30% then a 20% reduction is 6% absolute risk reduction – so 6 people in every 100 treated will not have a heart attack or stroke who would otherwise have had one. However, if your risk to start with is only 10% then to take the same statin for the same period of time will only give a 2% absolute risk reduction – or 2 people in 100 benefitting. The question is, what is the risk that works for you?

To wind the clock back?

I had to smile when I heard the news report on the latest research to be published in the area of dementia. It was not the research that caused my amusement – it was an important piece of work which will help to fill the gap in the evidence regarding the use of drugs such as Aricept in the treatment of severe dementia. Up until now the focus of research has been in mild to moderate disease, and the NICE guidelines reflect this by only giving approval for these drugs in the early stages of the disease. The research demonstrated, not surprisingly, that the drugs do not stop working as a sufferer moves from moderate to severe dementia, and that they effectively turn the clock back by an average of 3-4 months.

What made me smile to myself was the implication in the news that what the guidelines say must be what happens in practice, ergo thousands of patients must be being deprived of these drugs once they get to the advanced stages of the disease. In reality, while it may be easy to define the different stages of this tragic disease in a research setting, or in the controlled environment of a NICE guidance panel, in clinical practice the transition is much more difficult to ascertain. The amusing picture that came to my mind was that of a dial on the patient’s forehead clicking over from moderate to severe, with a group of white-coated doctors standing around the patient’s bed, solemnly shaking their heads before striking Aricept from the drug chart with a big red pen. It’s as ludicrous as it sounds.

So how do doctors apply guidelines? Well, it depends what sort of guidelines they are. If NICE declare that a drug cannot be used at all, then they will be adhered to quite strictly. If they advise that a drug should sometimes be withheld on the grounds of patient safety, then you can expect doctors to follow this also. However, to recommend that a treatment, that is likely to be beneficial and is suiting an individual patient, should be withdrawn on cost grounds due to a lack of evidence – well that is a different matter entirely. Doctors like to give patients treatment that they think will work, and the difficulty in defining what constitutes severe dementia gives sufficient wriggle room that in practice these drugs are rarely withdrawn on the grounds of simply adhering to guidance – at least in my experience.

So this research will help to clarify the situation, and to improve the guidelines, but will make little difference to patients on the ground. If we can wind the clock back for someone with dementia, then that can make a significant difference to their lives, and we should do just that  – but there need to be two significant caveats to that principle.

The first is that these drugs do not work for everyone. If the average gain is to reverse the progress of the disease by 3-4 months, then there must be some patients who gain more than this – even six or nine months perhaps – and others who gain less. For some this will mean nothing at all. Then there are side effects. Most patients feel fine on these drugs, but some will not get on with them – and this is a challenge with a patient with dementia. They cannot easily explain how a drug makes them feel, and may be getting side effects that we don’t know about. Only this week we were chatting over lunch about patients of ours with dementia who have had their drugs withdrawn simply because they were at a stage where they refused to take them any more – and sometimes they then got significantly better!

The second, perhaps more important, caution here is that we will not always want to turn the clock back. Dementia can be an interminably slow process both for the sufferer and the family, who can only look on and see their loved one regress as every month passes. If the situation three months ago was intolerable, why would you want to go back to it? Sometimes these drugs can help to settle difficult behaviour in a person who is confused, but dementia can get to a stage even beyond that, where the patient is incapable of feeding themselves, speaking, toiletting or even sitting in a chair. When you get to that stage, there is a fair chance that, far from wanting to wind the clock back, you might actually want to turn it forwards as far as you can.

New NICE Guidance on Caesarian Section – no major change in practice, but welcome nevertheless

The updated NICE guidance on the use of Caesarian Sections in obstetric care proved sufficiently newsworthy yesterday to receive widespread coverage, including on the BBC, and with good reason. The decision to opt for a planned Caesarian Section in an uncomplicated pregnancy has always been a controversial one, and the previous guidance stated that maternal preference alone was not sufficient to proceed with this option. This has now been overturned, and maternal choice has prevailed.

The change in the guidance has obviously stirred strong opinions – the BBC site had elicited 622 comments within 12 hours, and is now closed to further postings. Views range from the strong feeling that a woman’s right to choose has to take priority, to others who say we can’t afford it, and still more who question why on earth a woman would want to subject herself to an unnatural major operation in place of the wonderful experience of childbirth (usually posted by women who have been blessed by a very positive and rewarding experience of the latter). As a man, I couldn’t possibly comment!

I do think, however, that it is very difficult for a woman to be able to choose what is best for her as an individual when she feels that a perfectly valid option is being denied her. The previous guidance made the situation very difficult for her, and Trusts are undoubtedly under pressure to keep their Caesarian Section rate low. For women who wanted to consider this option, there was the very real danger that a discussion with their obstetrician would become a challenge to prove to him or her that your case was worthy to upset their statistics, rather than an unbiased discussion on the potential harms and benefits of Caesarian Section verses a trial of natural labour. If there is even a hint of conspiracy and denial of rights then this can seriously undermine the doctor-patient relationship and so lead to bad decision-making. Patients need to be able to believe that their doctor really does have their best interest at heart with the information and advice that they give, and to be at the centre of decisions made about their care.

In reality, few women want to choose a Caesarian for an uncomplicated pregnancy, and most are able to face the uncertainty and huge physical challenge of natural labour with great courage and strength – and the majority are delighted afterwards (if not usually during!) that they have done so. However, the fact that the majority are best served by this outcome does not mean that we should underestimate the fact that some women have very difficult labours that are far from rewarding, and for some the security of a planned operation is indeed the right choice. This is something the NHS should value sufficiently to find the necessary additional expense it may entail, and NICE has done well to make this advance for patient-centred care.

Where is the Evidence?

I had one of my increasingly rare encounters with a representative from the pharmaceutical industry this afternoon. As usual, it left me wondering when our society will have the courage to stand up to the giants of the industry, and insist that they show some real evidence before they are allowed to market their products.

The drug in question is a new form of pain-killer called Tapentadol. I was quite interested to hear about this product since I had only come across it for the first time three days earlier, and it seemed worthwhile finding out a bit more. The drug is a morphine-like pain-killer, and the major selling point is that it has a novel, dual mode of action. Pain can be classed as nociceptive (standard, hit your thumb with a hammer type pain) and neuropathic (pain caused by over sensitive pain nerves, as occurs for instance after a bout of shingles). We already have drugs that can work on each type of pain, and these include Oxycodone (which is similar to morphine and good for your broken thumb), and Duloxetine, which works on neuropathic pain. ‘All the power of Oxycodone and Duloxetine wrapped up in one molecule!’ the Rep proudly informed me.

Well, if it has the combined strength of two drugs, is it not reasonable to expect it to be more effective than one of those drugs on its own? Apparently not. The best data she could show me was that Tapentadol was no less effective than Oxycodone.

‘I thought you said it was more effective?’ I asked her.

‘Oh it is, it has a dual mode of action.’ she replied.

‘But this just shows it’s no worse.’

‘But we know it is more effective.’

‘And how do we know this?’

‘The consultants at St George’s are using it.’

Well, much as I am sure I respect the consultants at St George’s, this is not what I would call evidence-based medicine.

When a Drug Rep shows you data you can be sure of one thing – it is the best data they have in favour of their drug. What you have to worry about is the data out there that they are not showing you. If this was the best she had in terms of efficacy, then this drug is not yet ready to convince me about its novel new dual mode of action.

It’s at times like this that I am glad of organisations like NICE which will look at whether these new agents really are what they claim to be – and even the PCT which gives increasingly tight guidance on what should usually be prescribed on the grounds of cost-effectiveness. Whilst we might not like being told what we can and cannot do, these organisations stop doctors jumping on the latest bandwagon and are some of our best defences against being hoodwinked by the pharmaceutical industry.

Hmmm, I seem to have strayed into politics. Well, sometimes you just have to do these things. Rant over.

New Blood Pressure Guidelines – NICE for Doctors or Nice for Patients?

When a medical story hits the news it is always fascinating to see the details the media chooses to highlight. For the new NICE guidance on high blood pressure, published yesterday, the spotlight was firmly centred on 24-hour blood pressure monitoring (also known as Ambulatory Blood Pressure Monitoring or ABPM). Both the Today Programme  and the 6 O’clock news focused on this and nothing else – maybe this just demonstrates my lamentable BBC bias, and other news agencies took a broader view, but this is all I have to go on for the moment.

The new emphasis on ABPM is a worthy subject for the reporters to focus on – there is certainly a change away from recording blood pressure in the surgery – what is disappointing is that there was no room in the broadcasts for the role of Home Blood Pressure Monitoring (HBPM). HBPM is where a patient measures their own blood pressure using an automated machine, taking a range of recordings over a few days. I’m not sure why the reporters neglected to mention this option, but I suppose their editing has to be ruthless in an article that only has a few minutes of air time.

What is even more interesting is how the Guidelines themselves handle the variety of ways of measuring blood pressure. There is certainly clear movement away from surgery readings, with the NICE panel recognising that up to 30% of people can be wrongly diagnosed with high blood pressure if clinic readings are used alone. The guidelines then give the pros and cons of ABPM and HBPM – only they don’t. What the guidelines actually do is give the pros of ABPM, and the pros and cons of HBPM. Why is this?

Well, there are some good pros about ABPM. The main advantage of this technique is that it avoids what is known as ‘observer error’. As long as the machine is correctly attached, and the patient has a regular heart rate (neither ABPM or HBPM cope well with an irregular heart rate called atrial fibrillation) then the cuff will reliably inflate every half an hour and record the result in its memory, to be printed off later and analysed by the doctor. The ‘observer’ here is a nice, predictable, reliable computer – not much can go wrong. Being reliable means it is easy to study in research, and so there is plenty of good evidence in the medical literature that supports the use of ABPM. Good evidence and reliability are buzz words for the panels that write these guidelines – and rightly so.

Conversely, observer bias is a definite possibility in the use of HBPM. The guidelines state that up to 70% of people using them don’t stick to the protocol they are given (I wonder, if we are honest, how many doctors stick rigidly to the recommended protocol when we take a blood pressure in the surgery…) and up to 30% are not entirely honest when they record the readings that the machine gives them – a variation, I presume, on not being entirely honest with our doctor about how much alcohol we consume or how many cigarettes we smoke. There is also the concern that some patients, let loose with their own machine, might become neurotically obsessed with their blood pressure. These are all valid points. However, I believe that they betray a lingering mistrust within the medical profession of this unpredictable, seemingly irrational and altogether awkward component of both our research and our working week – the patient. All too often they don’t do what they are told, don’t accept our words of wisdom,  and just thoroughly mess things up. The problem with HBPM is it involves the patient too much for comfort.

Nevertheless, there is a concession that HBPM offers many of the advantages of ABPM – principally that the blood pressure is measured in the normal home environment – and it is recommended to use HBPM if a person is ‘unable to tolerate ABPM’. But hold on, when the guidance talked about ABPM there was no mention of it being difficult to tolerate! Note the language here – it is the patient who is unable to tolerate it – that awkward variable messing things up again! Is there to be no acknowledgment of the fact that ABPM might actually be intolerable?

I don’t know how much the NICE guidance panel consulted with patients when they updated these guidelines, but I can only assume that they did not talk to many who have experienced ABPM, or tried it for themselves. We used to own a machine at Binscombe. For every patient who got on with it reasonably well there was another who politely told me that they would rather not have to use it again – when what they really wanted to do was to throw the machine on my desk in a fit of pique and declare: ‘You try it then, if you think you’re so clever!’ I can’t say I blame then. The cuff inflates every 30 minutes, day and night for 24 hours. Many patients get very little sleep, and spend much of the time anticipating when it is going to go off next. It doesn’t ask if it’s a convenient moment to take a reading before it activates, and is as likely to fire up when you are tackling a tricky junction in the car on your way to work as when you are sitting comfortably on the sofa at the end of the day. It could take a reading just as you stand up to give a speech, try to have an intimate moment with your partner, or are engaged in a private moment in the bathroom. It is going to inflate with high pressure over the same part of your arm nearly 50 times during the 24 hours, and I have seen patients literally black and blue with bruises at the end of it.

Don’t get me wrong, in general I wholeheartedly approve of NICE guidance – they have brought a clarity and a consistency to medical care which was distinctly lacking before NICE came into being – and I welcome these new guidelines as much as any. I am delighted that the emphasis is shifting away from measuring blood pressure in the surgery, and this is in keeping with our approach at Binscombe, where we have been using HBPM increasingly over recent years. Somehow, though, I can’t see us scouring the medical catalogues to buy a new 24 hour blood pressure machine – and if instead we have to work with the unpredictability of our patients…well, isn’t that what we went into medicine for in the first place?