7971:1 – What will you trust when it comes to the safety of HRT?

You get used to outrageous medical claims in the press, but The Telegraph has truly surpassed itself today with its front page headline declaring that ‘HRT ‘is safe’ for postmenopausal women after all‘.

The article states that new research ‘has found no evidence that HRT is linked to any life-threatening condition’, and makes much of the fact that the new study followed women for a decade. There is a quote from Dr Lila Nachtigall, one of the study authors and a Professor of Obstetrics and Gynaecology at New York University who claims that: ‘the risks of HRT have definitely been overstated. The benefits outweigh the risk.’

Prof John Studd from London is even more forthright, saying: ‘Most GPs are afraid of HRT – they will have learnt as medical students that it is linked to health risks. But those studies that were replicated in the textbooks were worthless. They collected the data all wrong.’

These are bold statements, and so you would expect them to be based on a significant piece of research. The main study that Prof Studd so comprehensively dismisses is the British Million Women study – over 1 million women were studied specifically to look at the risk of breast cancer with HRT and it found a small, but significant, increased risk. To overturn the findings of such a significant piece of research would require something big.

So what is this new research? Well the article, as is so often the case, fails to tell you – but if you are still reading as far as the 11th paragraph you may start to have your doubts: the study followed 80 women. 80! Not 800 000, or even 80 000, but 80! To be fair, when you look at the study itself it’s actually 136 – 80 women on HRT and 56 without. So with 1 084 110 women in the million women study and 136 in this new, apparently game-changing research – that’s 7971:1.

What’s more, when you look at the new study in detail (and here I’m grateful to Adam Jacobs on twitter who managed to locate it) the study was not designed to look at the safety of HRT – the intention of the research was to answer a question about the effects of HRT on body fat composition, and any findings on the safety of HRT were only a secondary consideration. What is more, it is described as a retrospective cohort study – that means it looked backwards at the history of these 80 women, so if a woman had got breast cancer related to HRT she might not have been alive to take part in the study in the first place.

Even if the study had been designed to prove there was no link between breast cancer and HRT, the Million Women study suggests an increase of only 5 extra breast cancers in 1000 women taking HRT for 10 years – so 80 women would only have 0.4 extra breast cancers between them – meaning the study is far too weak to draw any conclusions at all. Oh – and the study was sponsored by Pfizer, who might just have a commercial interest in lots more women going on HRT.

The Telegraph was not the only newspaper to pick up the story, but it was by far the worst reporting among the broadsheets – The Guardian, for instance, picked up the small number of women in the study and tried to bring a sense of balance to its piece – just so long as you read past the headline and the first two paragraphs.

In closing, I would like to say one or two things to Prof John Studd of Wimpole Street. The first is that if you are going to have an official website it would be best, for reasons of probity, if you could include an easy to find declaration of interests; maybe I am being dense, but I failed to find yours. Secondly, GPs are not afraid to prescribe HRT – and we have learnt one or two things since medical school – but we do like to prescribe it after having a discussion with the woman concerned about the balance of benefits versus risk, as we like to base this on reliable evidence.

And for a woman considering HRT wondering what all this means? HRT remains the best way to control symptoms of the menopause, which can be very distressing. There is an increased risk of some cancers, but it really is quite small and many woman feel it is well worth taking that risk in order to feel well; have a chat with your GP about it.

 

The Saatchi Bill – Innovation or Obscuration?

What’s the difference between a quack and a pioneer? And how do we allow the next William Harvey or Edward Jenner to flourish, whilst protecting the public?

These are the questions at the heart of the Medical Innovations Bill, the basis of which is the belief that true innovation is being stifled by the fear doctors have of being sued, and that legislation is required to remove this barrier.

I found myself trying to answer these questions in the consulting room the other day when a patient asked me directly if she could have a syndrome I had never heard of before. She has a multitude of symptoms that I have been unable to explain, and her internet search had led her to the syndrome as a possible explanation for her situation. She was kind enough to give me time to do my own research, and we agreed to meet again to discuss it.

The syndrome in question (which I won’t name for fear of saying anything that could be misconstrued as libel) was unorthodox, but not implausible. It suggested that there could be a hormonal imbalance at tissue-level which was not reflected in abnormal blood tests, and high-level hormone supplementation was required.

But tissue-level biochemistry is still poorly understood. If bacteria in your gut can cause ulcers and crystals in your ear lead to vertigo, then I don’t see why some hereto unknown enzyme problem couldn’t lead to a hormone imbalance – unlikely, but not impossible.

Here, however, is where the theory started to break down into quackery: the proponent of the syndrome did not engage in the process of scientific enquiry, but named the condition after himself, set up a lucrative clinic offering untested (potentially harmful) therapy to patients outside the bounds of a clinical trial, and continues to offer such treatment despite being disciplined by his professional body.

When I made my conclusions about my patient’s diagnosis, explaining the background, thankfully she agreed with me.

So I am left with a simple distinction between true innovators and quacks. The former will be motivated by a desire to discover truth through rigorous scientific enquiry and external peer scrutiny, while the latter will come up with plausible, attractive theories and hurry on with treatments without stopping to examine the effects in an unbiased way

This is why we do not need Saatchi’s Bill, and we should strongly oppose it. A true innovator will not want to implement the Bill, while a maverick doctor may seek to exploit it. Their motivations for doing so may be benign – a desire to offer hope to the patient in front of them, perhaps, or an inability to admit the truth that really nothing more can be done – but the outcome will be the same.

The Bill is meant to encourage innovation where there is a dearth of clinical trials, but in such circumstances a true innovator will not complain about the lack of trials, they will create one.

The Bill seeks to provide safeguards so that proposed treatments are brought before fellow clinicians before being used. A true innovator knows the value of proper scrutiny as afforded by an ethics committee.

The Bill seeks to encourage treatments for patients who have no time to wait for clinical trials, but a true innovator will see the long line of future patients, and not allow decisions to be dominated by the suffering of those immediately before them.

Maybe our Health Secretary and Lord Saatchi should talk to someone like Barry Marshall, who jointly won the 2005 Nobel Prize for Physiology with Robin Warren for establishing the link between H pylori and peptic ulcer disease, and was so obsessed with finding the truth that he infected himself with the bacterium to study its effects – now that was true innovation. I wonder what he would think about the Bill?

The post was originally published by Pulse (free registration required)

On the Rebound

My Twitter feed has recently been subject to a series of promoted tweets from a company that sells decongestant nasal sprays. The brand behind these advertisements shall remain nameless (other decongestant nasal sprays are available), but I have been compelled to take to the keyboard because the spray is being recommended for the relief of symptoms of hay fever – which is just bad medicine.

I must make it clear that the company is doing nothing wrong – the spray is licensed for the treatment of hay fever and it is available without prescription, so they are well within their rights to advertise it in this way. That doesn’t mean I have to agree with them, though.

 

On the face of it, it seems reasonable to use a decongestant for hay fever – one of the symptoms is nasal congestion, after all. The problem lies in the issue of rebound congestion – sometimes known as rhinitis medicamentosa (medical speak for your medicines made your nose run). The decongestants might make you feel dramatically better in the short-term – as they reduce the blood flow, and hence the swelling, in your nasal passages within minutes – but they don’t do anything about the underlying cause. Worse than that, within a few days your nose can start getting ‘addicted’ to these sprays so that the congestion returns with a vengeance, requiring more of the spray to relieve the symptoms, leading to further rebound congestion and so on.

For this reason all decongestants have strict warnings on them that they are not to be used for more than 7 days. They are mostly used for treating colds, and since these last only a week or so that is not too problematic. For treating acute sinus pain, or relieving earache on a flight, they are fantastic, since these are short-term problems. Hay fever, on the other hand, will last as long as the pollen you are allergic to – April and March for tree pollens, May, June and half of July for grasses. So the adverts promote something that should never be used for more than a week, to treat a condition that will usually last at least 2 months. Even for those patients who have only very intermittent symptoms on high pollen days there are more effective treatments out there, in the form of antihistamines and steroid nasal sprays.

While the ‘S’ word can cause people concern, I sometimes describe steroid nasal sprays as being the polar opposite of decongestants. The latter make you feel better straight away, but do nothing for the underlying condition and will make it worse in the long-term, while steroid sprays do absolutely nothing straight away, but treat the underlying inflammation that is the problem in hay fever and will usually solve the problem in the longer term. The steroid dose is extremely low so that there are no side effects due to absorption into the blood stream. It’s better not to use them all year round if you can help it, due to thinning of the lining of the nose and nose bleeds, but then hay fever is seasonal so most people can have prolonged breaks from treatment.

As a doctor I feel especially powerless to stop people becoming dependent on decongestant nasal sprays; and some do become truly hooked – I have had some patients rely on them for decades. I know that my pharmacy colleagues are very good at warning patients not to take them for more than 7 days, and I can’t imagine any pharmacist recommending them for hay fever, but patients don’t have to speak to any health care professional to buy these products. They are categorised under General Sales Licence, which means that you can just drop them in your basket from the shelves of a supermarket and take them to the checkout – no-one will notice that you buy them every week, or advise you that it might be causing you such a problem.

How such a product was ever made so readily available, or achieved a licence for hay fever, I shall never know. There is no prospect of changing this, but perhaps by writing about it I can steer one or two people away from turning their seasonal allergy into a year-round problem of rebound congestion.

Intrinsa? Intrinsically Wrong

Few of us will have noticed the change in status of the testosterone patch Intrinsa last October. As a GP I have no patients who have been affected by it, and while a treatment for the controversial diagnosis of Female Sexual Dysfunction might be significant for a small number of women, it is hardly a life-threatening condition or a major public health priority. However, we would do well to take note, because it heralds a new low in the behaviour of the pharmaceutical industry as they try to maximise profit, and has implications not only for the resources of the NHS, but also patient safety.

Intrinsa is a testosterone patch, and was one of the few such products licensed for use in women. In October 2012 Warner Chilcott, the company that held the rights to market Intrinsa, took the unusual step of voluntarily withdrawing its product licence ‘for commercial reasons’. Given the high costs involved in obtaining a product licence in the first place, it is hard to see how this could bring commercial benefit – until you follow the story a bit further.

Ben Bryant of The Daily Telegraph has been drawing attention to the activities of the pharmaceutical industry in a series of articles in the last two months, and has highlighted the situation with Intrinsa in his latest article. What Warner Chilcott have done is to maximise profit by exploiting the financial regulations surrounding licensed and unlicensed medicines – with the former having to abide by an agreed price cap while the latter exists in the mysterious world of the unregulated ‘specials’ market, where the drug company can charge whatever they want – frequently at outrageously high prices.

Within a month of the change, the ‘last batch’ of Intrinsa (sufficient for ‘the foreseeable future’) was acquired by another company HFA Healthcare, who were quick to point out their altruistic motive to ‘ensure continuity of medication for patients,’ but rather more reticent about mentioning the price hike – from £26 per pack to £395 per pack.

We have been here before with far more significant drugs – Epanutin was acquired by Flynn Pharma last year, with a 23-fold rise in the price and a great deal of worry for patients. What is new about is scenario, however, is the loss of the licence. A Licence is not just a mechanism to allow the pharmaceutical company to promote its product; it is a source of protection for both the doctor and patient. It provides security that a medicine has been properly tested, has safety data approved by an independent body (in this case the European Medicines Agency), and has been deemed to be effective in treating the condition in question. It is the medical equivalent of a Kite Mark.

The absence of a licence means prescribing a drug off-label. Doctors are used to doing this where treatment is required and no licensed product exists – the patient cannot always wait for the time-consuming processes involved – but this is because a licence has never existed, not because it has been withdrawn for purely commercial reasons. When a doctor does prescribe off-label in this way a doctor has to take extra responsibilities, or, to quote the MHRA:

The responsibility that falls on healthcare professionals when prescribing an unlicensed medicine or a medicine off-label may be greater than when prescribing a licensed medicine within the terms of its licence.

Put crudely, if something goes wrong you can’t sue the drug company as the medicine was used in a way that they did not recommend. The patient is more likely to sue the doctor, or not be able to get compensation at all if there is a problem; the drug company is able to wash its hands, and say ‘nothing to do with us.’ It is the equivalent of selling an electrical appliance, but withholding its 1 year warranty ‘on commercial grounds’, only the patient isn’t able to shop elsewhere, since there is no other licensed product to turn to.

Withdrawing a licence is not just a matter of finances, a way of a company balancing its books or a headache for the NHS drug budget – it is a patient safety issue first and foremost and this practice needs to be investigated and stopped in its tracks before the industry tries it out again – this time with a drug that really matters.

Who Gave Tesco the Right to Shape Our Children?

I clearly missed the moment when we decided to appoint supermarkets as the powers that should determine our social norms, but it has become clear recently that this mantle has been assumed by at least one of these marketing giants. My attention was drawn to this when the campaigning organisation Let Toys be Toys discovered that Tesco was advertising its chemistry set as ‘for boys’, while its Hotpoint cooker was labelled ‘for girls.’

We need to stop and think about this for a moment – if it does not shock and outrage us in the 21st century, then it certainly should. Surely we have moved on from any suggestion that chemistry is only for boys (were the struggles of Marie Curie and Rosamund Franklin for nothing?) And as for the kitchen…

Can we imagine a school separating children by gender in this way? There would be outrage, surely? Even Michael Gove would think it was old-fashioned!

What is revealing is Tesco’s defence of their actions. When Let Toys be Toys challenged them about the signs on Twitter, they replied with:

So, what they are saying is that they have conducted market research and that is what dictates their policy. The fact that any ethical analysis of the situation can only conclude that toys do not need to be defined by gender apparently has no bearing – the market research (in other words, what sells) trumps any social obligations Tesco might be troubled by.

After some outrage on Twitter (helpfully stimulated by Ben Goldacre) the Tesco account went mysteriously quiet. Subsequently they have apologised for ‘causing upset’ (always apologise for upsetting someone, never for being wrong) and have promised to update the chemistry set as being ‘unisex.’ This they have done, while the kitchen remains distinctly ‘for girls.’ The kitchen is pink – shocking pink – is that enough of a reason to label it for girls, or should we question why on earth a kitchen should be pink in the first place? The answer is clear from the description of another kitchen in the same range:

CookerIt’s not about pink then…

Since then there has been media attention, and Tesco have apparently stated on Watchdog that they will ‘be conducting a review of the way it categorises its toys.’ Why a review and not just an apology and immediate change? Is it that hard? They have decided to change the chemistry set without requiring a review, but I can only assume that working out how to categorise a ‘Wild physic and chemistry set’ is more complicated, since it remains like this on their website:

Physics setWhy does this matter so much? And why talk about it on a health blog? Well, I don’t think we should under-estimate the subversive influences on how we shape our children, or the impact that this will have on their subsequent health as adults. Educational attainment is closely linked to health, and being told you can or can’t do something could have an enormous impact on a child. If parents wish to point their boys towards science, and girls to the kitchen, then that is something I may not agree with (my father is a chef, my wife a scientist, so I’m hardly likely to), but neither should I interfere in another’s parenting without very good reason. Tesco, on the other hand, are not parents and should not presume that they have the right to stereotype in this way.

And when it comes to stereotyping, it is not just how we educate our children that matters to health, but how we feed them. It is nearly a year since Tesco assured me that they would remove the direction to ‘Children’s cereals’ from all their stores, after I pointed out the harmful health message implicit in the signs. Well, as for my local store, I am still waiting…I imagine they are busy conducting a review.

The Marketing of Epanutin – Re-energising a Product for an Underserved Population, or Big Pharma Behaving Badly?

Imagine if you will that, through no fault of your own, your life depends on Widgets. You need to have a Widget at all times – in fact a constant supply of them as a Widget is only good for a day. If you run out of Widgets there is a real risk that something terrible will happen.

Thankfully you know someone who makes just the Widget you need. His name is Phil, and he says he makes Widgets because he cares about you. Then one day Phil writes to you and tells you he won’t be able to sell you Widgets any more, but not to worry as you will be able to get them from someone he knows called Fred. In fact, you don’t need to worry at all because, although Fred will call them Gizmos, they are actually still Widgets under a different name – that is because Phil will still be making them just as before; he will sell them to Fred who will then label the Widgets as Gizmos and sell them to you.

It takes a little while to adjust to this news – Widgets are something you depend upon after all. You trust Phil, though, and reconcile yourself to using Gizmos instead of Widgets and order your first supply from Fred – only to find that where a supply of Widgets cost just 66p, the same number of Gizmos will set you back over £15.

It’s the sort of behaviour we might expect to find in the back-street supply of illegal drugs – but what if a Widget is actually an important anti-epilepsy medication, while Phil and Fred are the Pharmaceutical companies Pfizer and Flynn Pharma? For that is exactly what has happened.

Pfizer have long been the manufacturers and distributors of Epanutin (generic name Phenytoin), one of the oldest drugs used in the treatment of epilepsy. On 24th September 2012 they agreed to transfer the marketing authorisation rights of Epanutin Capsules to Flynn Pharma. All GPs received a letter from Flynn Pharma advising us of the change, and the fact that we will have to change the prescriptions of all our patients on ‘Epanutin Capsules’ to read instead ‘Phenytoin Sodium Flynn hard capsules’. This is annoying in itself as it requires unnecessary work to make the switch, and no doubt some patients will be concerned or confused by the change. The letter was reassuring, however, as the new drug is exactly like the old one – so exactly in fact that it is still being made by the same people at the same site in the same way, only the packaging has changed.

What Flynn Pharma neglected to mention, however, was the price hike – from £0.66 to £15.74 for a packet of 28 capsules. How can this possibly be justified? Flynn Pharma’s website states that:

At Flynn Pharma, we aim to rediscover tried and trusted branded pharmaceutical products. We re-energise products for underserved patient populations

Epanutin is not a drug that needs to be re-energised. Doctors know how it works and, until recently, where to get it from. The ‘underserved patient population’ in question does not need this drug to be rediscovered or remarketed, what it does need is a reliable, trustworthy source of supply. No other justification for the change has been presented to me and, unless there is some crucial piece of the puzzle I am not party to, the only justification I can see is Big Pharma wanting to make new money out of an old drug.

Of course, it won’t be the patient paying the extra cost, but the tired old, uncomplaining all-absorbing NHS. And I will have to go along with it; my options are very limited. No-one else is makes the capsules. There is a liquid version, but the doses are not equivalent. While there is a tablet form which is cheaper, there is a caution in the British National Formulary which states that changing from capsules to tablets could possibly cause problems in some patients. If there is one drug I don’t want to mess about with it is phenytoin. Minor changes in dose can lead to major differences in blood levels, which could trigger a seizure. For a patient with epilepsy a single seizure, as well as being unpleasant and potentially hazardous, can mean losing your driving licence for 12 months. No matter how angry I feel about this, or how low I feel the risks to be, the stakes are too high for me to ask any of my patients to change their medication without very good reason.

I don’t know how this change has been allowed to happen, but I would like to find out. Which organisation fights for the NHS here? The Medicines and Healthcare products Regulatory Agency (MHRA) decides if a drug can be licensed, but not if the NHS can afford it. The National Institute for Clinical Excellence advises doctors on which treatments can be afforded, and which offer best value for money, but does not seem to have a role in price-setting. If there is a body that is responsible for protecting the NHS from this sort of behaviour then I can only conclude that they are not doing their job properly – and if there isn’t, then there jolly well should be!

Early Diagnosis of Dementia – Cui Bono?

The Roman Senator and Lawyer Cicero famously popularised one of the most fundamental legal arguments in criminal debate: Cui Bono – ‘who benefits?’ The logic of the argument is that you will often get to the perpetrator of a crime if you start to ask yourself who it is that is its greatest beneficiary.

The Government’s National Dementia Strategy is hardly a crime – there is much to be praised and welcomed within its 102 pages – but the emphasis on early diagnosis leaves me feeling decidedly uneasy, and when I apply Cicero’s method to the situation I start to understand why this might be.

The issue I have with early diagnosis of dementia is that it is not the same as prompt diagnosis. Prompt diagnosis relates to someone with symptoms, who is seeking to know what is the cause of the problem, and where delay in reaching an understanding of their situation (ie a diagnosis) is never a good thing. That does not, however, mean that early diagnosis is always a good thing – since this also involves encouraging people with mild or no symptoms to look for early signs of the disease and to seek treatment.

In the strategy document there are compelling anecdotes about patients who have suffered with dementia for prolonged periods who have asked for medical help but had huge delays in receiving it, and the Government is right that this is unacceptable. However, whenever I hear about the dementia strategy in the news, or receive updates from our commissioning group about plans to implement it, the main emphases often seem to be on training for GPs so that we can recognise the early signs, and screening older people to test their memory. So the anecdotes tell us that diagnosis in patients who are already presenting to their GP is often not prompt enough, but the solution is to make the diagnosis more often.

So Cui Bono when it comes to early diagnosis?

The Pharmaceutical Industry: Without doubt the major beneficiaries of early diagnosis are the companies who manufacture the drugs used in the treatment of dementia. Most people with a diagnosis of dementia will end up on them, and many will stay on them for all or most of the rest of their lives. If a patient is diagnosed a year earlier then the drug company will profit from an extra year of prescriptions. If more people are diagnosed, then their client base will increase accordingly. Pharmaceutical companies need to look to their future market, and old age and dementia are reliably expanding year-on-year, so it makes sense that companies are investing heavily in this area. This is not necessarily a bad thing – I am not against businesses making a profit – but the question is, will all these extra prescriptions be to the benefit of patients?

The Politicians: A second clear set of winners from this drive for early diagnosis are the politicians. Dementia affects many of us one way or another, and causes most of us anxiety as we look to the future, and so there is high political capital to be made from seeming to be at the forefront of improving the lot of dementia care. What is more, were a high-profile politician to question the value of early diagnosis, there would be significant risk that they would be misunderstood or misquoted, and the damaging headlines accusing them of ageism would be easy to foresee. There are easy political wins to be gained here, also. There is little cost to declaring that GPs need better training, or investing in a computerised screening tool, and this allows our political leaders to sidestep the real issues of under-investment in nursing and social care for older people.

The Experts: While I have every respect for my specialist colleagues in the field of dementia care, I am concerned that we are overly reliant on the opinions and enthusiasm of experts in the developement of medical strategies and guidelines. The field of old age psychiatry has been much neglected by the medical profession over the years, and now that there are treatments for dementia it is finally coming of age and gaining the attention it deserves. It would take a bold consultant psychiatrist indeed to publicly question the wisdom of early diagnosis – it really would be biting off the hand that feeds. While it would be foolish to develop a strategy without receiving input from clinical experts, we must be more willing to question their objectivity and critically appraise their judgements.

The Patients: Ultimately, this is all to the good if everything is to the benefit of patients, but herein lies my problem – I am yet to be convinced that early diagnosis (as opposed to prompt diagnosis) is of any benefit at all. The medications which are prescribed do not alter the course of the disease. They effectively turn the clock back an average of six months, and it makes no difference whether we make this adjustment now or in two years time – the end position will be the same.

There are two main reasons why I might not pursue a referral in a patient who was possible early signs of dementia. The first, and most important, is resistance from the patient – and who can blame them. Attaching a diagnostic label turns a person into a patient, and often this comes with significant personal cost; we should only recommend this when the benefits clearly out-weigh this cost. While we must keep trying to reduce the stigma associated with dementia, we have to acknowledge that for many it remains a frightening and distressing diagnosis and should not attach it lightly.

I would not stand in the way of a referral for dementia, but the second reason why I lack enthusiasm for it is that the service currently available to me is just not good enough. It is woefully underfunded and the worthy people involved in dementia care are spread far too thinly. There is insufficient support available from dementia specialist nurses, little family support and education and inadequate social care. As a consequence a referral is often reduced to an infrequent clinic review and a decision about medication.

Of course, if we swamp the system with a swathe of new patients this might improve the service in time, as resources would have to be poured in to resolve the inevitable crisis. Crisis management, however, is one thing that is never to the benefit of patients.