The Polypill – Holy Grail or Fool’s Alchemy?

The Daily Express headline of an all-conquering Polypill waiting in the wings, ready to save thousands of lives and rescue the NHS finances, has become almost an annual event. This year’s offering is no disappointment, and its particularly misleading headline –Ten pence pill could help you live 8 years longer was rewarded with a front page spread.

The study that provided this exciting headline was based in India, and compared the use of a single combination pill with usual care for patients with established heart disease, or felt to be at risk of heart disease. The combination pill contained aspirin, simvastatin for lowering cholesterol, and two blood pressure drugs – lisinopril and either atenolol (a beta-blocker) or hydrochlorothiazide (a diuretic). Far from showing any reduction in heart problems, however, the study actually only demonstrated  increased adherence to medication in the treatment group, and a modest reduction in systolic blood pressure and LDL cholesterol compared with the control group. There was also the slightly awkward bias in the study whereby the treatment group received their medication for free, while the control group had to pay for any medication they received – a factor which could surely account for all the study findings at a stroke.

Whenever I hear of yet another study involving the Polypill, I find myself wondering why on earth they bother. Even if they finally break the mould and actually demonstrate benefit that means something to patients – rather than just improving the numbers that doctors measure – are GPs and their patients really going to want to start taking the 4 in 1 pill?

If you needed to be on that exact combination of tablets then there is no doubt that to swallow one pill rather than 4 would make life easier, but does this outweigh the downsides of coupling together 4 very different drugs into one preparation? None of these tablets will make a patient feel any better – they are only used to reduce the risk of something happening in the future, such as a heart attack or a stroke. The biggest issue when starting them, therefore, is side effects. No side effects is the goal, but what are the chances of someone having no side effects if they start 4 drugs all at once? And if they do get a side effect, how are they to know which tablet is causing it?

Some side effects are typical for a type of drug, an irritating cough can occur with lisinopril for instance, and so the doctor may well be able to guess the culprit – but a side effect with even one component in the Polypill will mean having to divide it into its constituent parts and start again. The prospect of having to unpick this magic medicine on a regular basis does not fill me with enthusiasm.

Then there is the need to respond to the ever-changing face of medicine. Aspirin, for instance, was used extensively in patients who were thought to be at risk of heart disease, but more recently the advice has changed to only use it in those with established disease. In fact the twists and turns of advice for this particular drug has an extensive history which caused me to write an early post in this blog. All it would take would be for the advice to change once more, and patients on the Polypill would need to be recalled, with their medicines changed, resulting in all the attendant uncertainty, anxiety and confusion that inevitably accompanies changes in medication.

The current direction of travel in healthcare is towards personalised medicine, with an emphasis on tailoring a drug cocktail to match the exact physiological needs of an individual’s biology. While I would prefer that there was an equal focus on tailoring medications to an individual person’s informed choice and preference, it can only be a good thing to try to personalise treatment in this way. The Polypill seeks to take us in the opposite direction and I remain deeply sceptical about any benefit it may have for our society.

The researchers behind this work are boundless in their enthusiasm, however, and so future studies will no doubt pop up from time to time  – well, at least it keeps a journalist employed at The Daily Express!

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).

Quick Post: Best not wash your pills down with grapefruit juice

Food-related health scares usually involve a tenuous link with either cancer or heart disease, and the associated headlines warning us to avoid the offending substance, or eat it by the bucket-load, are usually best ignored. The recent news reports concerning grapefruit juice, however, are worth heeding.

Grapefruit juice is good for our health, being low in fat and high in both fibre and Vitamin C. It does, however, contain a chemical which can affect the way our bodies handle certain medications – in particular some statin drugs used for cholesterol, and blood pressure tablets called calcium channel blockers. The result of this is that the tablet stays in the system much longer than it should, and to wash your pills down with a glass of grapefruit juice could have the same effect as taking an over-dose. While doctors do know about this problem, it probably needs to show up on the radar more often both for doctors and their patients.

The list of medications affected can be found here, and a pharmacist would be the best source of information for anyone who wants to check if their own tablets are affected.

Finally, I do feel obliged to make a declaration of interests here: I really do not like grapefruit – I wonder how I’d feel if it were orange juice?

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?