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)

Raising Awareness – Do We Know What We Are Doing?

There was an interesting discussion on Radio 5 Live recently between Glasgow GP Dr Margaret McCartney and Kris Hallenga, the founder of the CoppaFeel breast cancer awareness charity. The interview was arranged in relation to an article Dr McCartney wrote for the BMJ in the first of her new weekly column for the journal, which criticised The Sun newspaper’s rather hypocritical Page 3 campaign to encourage young women to regularly check their breasts for lumps. Whatever you might think of the piece, you have to admire Dr McCartney’s boldness for taking on both a national daily newspaper and the emotive power of the Pink Ribbon for her induction to the column!

The interview exposes how screening for disease and responding to symptoms are so often blurred in the media and by health campaigners – whether this is due to simple ignorance or a deliberate ploy to increase the power of the campaigns is uncertain, but that it is helpful is without doubt. The Sun’s campaign calls for the screening of asymptomatic women through regular breast self-examination, and Dr McCartney’s assertion is that the benefits and harms of this strategy are not sufficiently understood to be able to promote such advice, and what evidence we do have suggests it may do more harm than good. Ms Hallenga, on the other hand says that she ‘ignored her symptoms for so long’; ignoring the symptoms is not the same as failing to remember to check yourself when you don’t have symptoms – there is something more going on here, which brings me to a fundamental problem with ‘awareness raising’ health campaigns.

The logic of raising awareness goes like this: people aren’t seeing their doctor quickly enough about a certain disease – this must be due to a lack of knowledge, understanding and awareness of the condition – there should be a campaign to raise awareness – people will be better informed and see their doctor more quickly – lives and money will be saved. If we were all computer programmes and responded in a predictable way to data input this would work a treat, but people are far more complicated than that.

There are many reasons why someone may choose not to see their doctor when they have significant symptoms. Ignorance may be one of them, but in this day and age of instant health information courtesy of Google, it is surely less of a factor than it used to be – the danger is now the converse, that too much information may be having a detrimental effect. If a woman finds a breast lump – whether by chance or through a belief that she should check herself – she is unlikely to be unaware that breast cancer is a possibility, and yet some will delay seeing their GP despite this knowledge. Other factors must play a part: fear of what might happen next; complex self-denial as we convince ourselves that ‘this can’t be true’; embarrassment; business and the attitude that ‘I haven’t got time to be ill’ are all reasons why someone may not see a doctor – attitudes that might be improved by an awareness-raising health campaign, or might just be hardened by it.

Awareness raising is usually championed by politicians whose motive is to improve a statistic or – for understandable reasons – by those with an emotional connection with the disease in question. The problem with this is that the focus is heavily biased towards those with the disease, with little consideration given to the potential harm to others who may be caught up in the campaign. The justification for this is often that it brings reassurance to those who are checked out and found to be ok – but we should question the merit of a campaign which brings peace of mind to those who have been made anxious by the very same campaign in the first place.

The ‘cough for three weeks could be cancer’ strategy is a good case in point. As with all GPs I have seen more patients with a cough since the adverts appeared – usually non-smokers who are very conscious of their health and would never ignore symptoms for very long – while I am aware of smokers who have been put off seeing their GP by this very campaign because they don’t want to be given bad news. There is rarely any attempt to see how people will respond to these health messages – little consideration given to the fact that the same message might harden the resistance of those who should seek advice while unhelpfully altering the health-seeking behaviour of those who should not. We need to be bolder in challenging this, even if, like Dr McCartney, we end up being accused of acting ‘dangerously’.

Sometimes, though, if you can’t beat them you have to join them, and so I would like to launch my own awareness raising campaign. It’s very simple and it goes like this: ‘Health Awareness Campaigns can do more harm than good – use with caution, apply common sense, and trust your instincts’.

This post was originally posted in Pulse magazine (free subscription required)

Would We Have the Nerve?

It will remain to be seen whether or not the release of 25 year follow-up data from the Canadian National Breast Screening Study will prove to be a game changer, but what if it did? What if its findings – that regular screening mammograms have no impact at all on mortality from breast cancer, and result in harm from an overdiagnosis rate of 22% – were proved to be irrefutably true? What then? Would we have the nerve to act? Could we ever give up the UK screening programme?

There can be no doubt that if the Canadian study were the only research available then mammography could not be recommended – we would conclude that it does more harm than good and be done with it. We should never rely on one study, of course, and other studies have shown routine mammography in a more favourable light. It is, however, the only study of significant size to be undertaken in the modern context of more effective breast cancer treatment and it is not the only time in recent years that mammography has been brought into question. So what if we were to believe its results?

What would happen if the UK National Screening Centre (UKNSC) were to withdraw its support for breast screening? We are used to new programmes being introduced, but not an established one being cancelled; after 35 years of endorsement and public health advice exhorting women to take part in screening, it would be quite an about-face to tell the population that it wasn’t such a good idea after all.

There would be all the mobile screening units for starters – what would we do with them? Replace the x-ray machines with ultrasounds and expand the aortic aneurysm programme? Cut our losses and sell them off to a haulage company? What about all the staff involved in delivering the programme? Or the expertise the NHS has acquired in reading mammograms? There would still be a role for the x-ray in symptomatic women, but there would be huge over-capacity if the screening programme were to be stopped in its tracks. I’m certainly not rushing out to buy shares in a company that makes mammography equipment.

More of an issue, though, is the political challenge that any change in policy would encompass. It is well-known that no matter how compelling the argument might be for closing a hospital, trying to actually do such a thing is usually akin to political suicide – would the same be true for whichever unfortunate cabinet minister was left to announce the cessation of screening mammograms? Would the move be seen as anti-women? What would the pro-screening lobby have to say? There are enough men who are angry about being ‘denied’ a national prostate screening programme despite the evidence that it would do more harm than good. The belief that early is always better, and knowledge is always good are so deeply ingrained that they are often maintained despite any amount of evidence to the contrary.

Any woman who has had to endure the rigours of treatment for a breast cancer picked up on a mammogram can be expected to believe wholeheartedly that the whole process has saved her life – how else could anyone face going through such difficult treatment? What, then, is she to think if she hears of other women being denied the same chance to live? Can we expect everyone to make a clinical assessment of the evidence on such an emotive issue as breast cancer?

Perhaps the biggest hurdle of all, however, will be the NHS Mandate. Enshrined within this document is a drive to bring down five-year cancer survival rates; those figures that are thrown at the NHS from time to time as the UK is told how poorly we compare with the rest of Europe. The best way to keep five-year survival figures low is to concentrate on screening – catch it earlier, survive longer – and not to worry too much about mortality rates. If the Government ever sanctioned the cessation of the breast screening programme we would slip even further down the league tables and the goals of the Mandate would be harder to reach – even if it was better for the health of the nation, this could be too much for those in power to stomach.

I don’t know where the evidence will move from here – more studies perhaps? Another Cochrane review? Perhaps the UKNSC will deliver a verdict. What really matters, though, is whether we could ever act on the findings; if we have been doing the wrong thing for the last 35 years, could we ever find the nerve to change?

This past was originally posted in Pulse magazine (free subscription required)

Cancer Diagnosis – Woeful Performance, or the Reality of General Practice?

As GPs we get used to being beaten up in the press; hauled over the coals for this lamentable failing or that shocking inadequacy. It is still a bitter pill to swallow, however, when you are lambasted for failing to achieve a target that belongs to someone else.

The BBC reported recently that

Under NHS targets, 95% of people with suspected cancer should be seen by a specialist within two weeks. But the data indicates that this target was missed in more than half of the 4,000 GP surgeries sampled.

The article goes on to report how woeful our figures really are – 59% of GP practices achieve less than 50% and some practices less than 10%. A cancer target of 95% where only 10% is achieved? My goodness we are bad, aren’t we? Before we all decide to give up and let someone else have a go, however, let’s just have another look at that target, and what the figures from NHS England actually mean.

There is indeed a 95% target around cancer referrals, and it is this: 95% of those patients referred by their GPs under something called the Two Week Rule (TWR) should be seen within those 2 weeks. It is a target for hospitals to make sure they really do see patients within the 2 week period, with 5% wriggle room for those few inevitable cases where the system breaks down. The NHS England league tables, on the other hand, are not based on a target at all. They have simply looked at all those who have been diagnosed with cancer, and then the percentage of those cases that were referred under the TWR, as opposed to any other route. The BBC report mystifies me – is this just rank ignorance and inadequate research, or do they really know what they are talking about, but find that a little judicious muddying of the waters makes for a better story?

So what of the NHS England data? Does it make sense to rank practices on the basis of how many cancer patients are seen under the TWR, and does the implication that the highest percentages indicate the best practice hold water? There are many routes a patient might take on their journey to a cancer diagnosis, and surely what really matters is not how they got there, but whether or not there were unnecessary delays along the way. Many of my patients, for example, are diagnosed through the breast and bowel cancer screening programmes. Now these patients could be referred back to me with their abnormal mammograms and bowel tests for a TWR referral – it would do my figures no end of good if they did – but that would hardly improve patient care. Then there are those patients I see where a TWR referral is far too long – acute leukaemia, for instance – and emergency hospital admission is required. Am I to regret getting on the phone to the on-call team because I might slip a place or two in the league table?

Other patients, quite rightly, will take themselves to accident and emergency when they first present with symptoms – a first seizure from a brain cancer, for instance, or a sudden bleed from a stomach cancer; still others will be diagnosed with cancer after an appropriate period of watchful waiting in the hospital – a slowly rising PSA for instance. All of these patients appropriately referred and diagnosed without delay and without mention of the TWR. What is the ideal percent of patients who should be referred under the TWR, I wonder? Even NHS England states that the figures are ‘not a clear measure of performance’.

Then comes the harder part, those patients who do present to their GP, who have cancer and may have typical red flag symptoms or may have an illness which is far more vague and challenging. We have to be careful here, because there are too many real life stories of patients who see their GP and are not listened to, or are fobbed off; patients who attend again and again, knowing there is something seriously wrong with them, but not feeling sufficiently empowered to insist on action being taken. We must not dismiss these stories, and there is always the need for doctors to improve the care they give, but neither should we be so afraid of missing cancer that we become defensive. The only way that I could guarantee that I never miss a case of bowel cancer would be to refer every patient with bowel symptoms for a colonoscopy under the TWR. My TWR percentage would be magnificent, but my local bowel consultants would be tearing their hair out and, more importantly, I would be putting my patients through unnecessary anxiety and investigations.

General practice is about dealing with uncertainty, knowing when to refer and when to spare the patient from a referral. We have learnt to tolerate this, and so do most of our patients when we talk to them one to one, but our society is becoming increasingly intolerant of any uncertainty. Politicians and the charitable sector are too quick to issue sound bites about their patient care without seeing the bigger picture. Indeed, Stuart Barber, from Beating Bowel Cancer, said it was ‘intolerable’ that patients were having to wait. I don’t want any individual patient with cancer to have to wait either, but we have to realise that the more sensitive we make our TWR criteria, the less specific they will become – and the more patients we have to put through the trauma of a TWR referral, with all its attendant worries and the risks of investigation.

The Joy of the Irrational

When I returned from the Royal College of GPs Annual Conference recently, my brain was left buzzing with ideas, keynote messages, ambitions, anxieties (quite a few anxieties…) and dreams about the future of General Practice. Oddly enough, though, there was one thought that kept bubbling to the surface in the cognitive soup of my mind – out-competing the words of the many excellent high-profile speakers for my attention – and it came from a 5 minute presentation of a piece of research on the humble mole (the dermatological rather than mammalian variety).

Apart from being an excellent (and award-winning) piece of research, it gave an insight into the peculiar interaction that happens between the doctor and the patient, and the fact that, try as we might to rise above our weaknesses, we remain deeply irrational beings.

The study by Fiona Walter and her team evaluated the effectiveness of a piece of equipment called MoleMate, which is a non-invasive system for evaluating suspicious moles for the possibility of melanoma. The researchers compared the results of using a best-practice 7 point checklist alone, with the use of the 7 point checklist combined with MoleMate. The hypothesis was that the addition of MoleMate would reduce the number of unnecessary referrals by picking up a higher proportion of the significant lesions.

The results of the study in fact showed that MoleMate did not improve the appropriateness of referral, and was actually less efficient than best practice alone, since it resulted in significantly more referrals. So far, so good – let’s not bother to get this particular bit of kit for the practice, well we weren’t planning to anyway so no loss there. What is fascinating about the research, however, is the finding that both the doctor and the patient preferred the MoleMate arm of the research – they found it more reassuring to have the additional guidance of technology, even though the study found the outcome was better without the piece of kit.

I’ve been wrestling with this one ever since. The allure of technology grips many of us, and for some bizarre reason we often prefer to place our trust in the evaluation of a gadget made by fallible humans we can’t see, than the evaluation of the fallible human we can see. The obvious conclusion to this piece of research is to dispense with the machine, and yet we know that using the machine meant that people were more satisfied with their consultation and felt more reassured. If you had MoleMate sitting in the corner of your consulting room, therefore, would you be able to resist the temptation to reach for it from time to time to make your patients happier? It’s bad medicine of course, but then if your patients go away more reassured, is it really so bad?

In this instance I don’t think I could countenance using technology I don’t believe in, but it got me thinking about the things I do in the consultation which may not be so very different. For instance, I usually make a point of examining the head in someone suffering from headache. Except in rare circumstances, such as temporal arteritis, I know that my examination will make no difference to the outcome, but it just feels right to do it. When you have pain somewhere, you expect the doctor to assess where it hurts. I don’t want my patients to leave the consulting room feeling inadequately reassured, thinking to themselves ‘he didn’t even look at my head.’ And yet, if I know that my examination is, in a sense, a sham, as it won’t add anything to my assessment, in what way is this any better than MoleMate? Or, put another way, is MoleMate just a high-tech version of that ancient therapeutic act of doctors – the laying on of hands?

I don’t have the answers. I’m certainly not going to start recommending a new piece of equipment without a sound evidence-base behind it, but I’m strangely uplifted by the results of this study – because it is the unpredictable nature of the way we humans behave that keeps medicine interesting, and the complexity and challenge of communication between the doctor and patient that keeps me motivated.

This post was originally published in Pulse magazine (free registration required)

Can You Walk off the Risk of Breast Cancer?

One of this week’s health stories is typical of how rather unexciting research can reach the headlines by virtue of its association with a condition like breast cancer, but it also serves as a good example of two of the most common sources of sloppy reporting that plague health stories – which makes me think it a subject worthy of a blog.

The research relates to the possible effect of exercise on the risk of developing breast cancer, and the headline is Walking ‘cuts breast cancer risk’. If true, this is hardly an earth-shattering discovery. Perhaps it will add in some small way to our understanding of the mechanisms involved in the development of cancer, but this is for the journals to worry about. When it appears in mainstream media, the point is surely whether it means anything to an individual concerned about her breast cancer risk – in other words, if you want to reduce your risk of developing breast cancer, should you take up walking? Unfortunately, the way the results are reported makes it very difficult to answer this question.

 

Problem 1: associations are not the same as cause and effect

The first problem is that the study has made an observation, which has been presented as a cause. The researchers did quite a simple thing: they arranged for a group of over 73 000 post-menopausal women to complete a questionnaire at intervals over a 17 year period from 1992 to 2009, asking questions about how many hours walking the women did, and any diagnosis of breast cancer. They found that those who walked for 7 or more hours per week were less likely to have been diagnosed with breast cancer than those who walked for 3 hours or less. This does not mean that the walking caused the reduction in risk, however. It may well have done, but it could have been some other factor. There could have been a different cause that was linked to both breast cancer risk and the amount women walk. For instance, walking less could be linked to obesity, which could explain the extra breast cancer risk.

The researchers were aware of this problem, and tried to exclude some factors – for instance, it was not due to those who developed breast cancer being more overweight than those who did not – but they can never exclude all of the possible confounding influences. For instance, it may be that those who walked less were more likely to have other health problems, and the increased risk of breast cancer was in some way linked to this.

In my experience, observational health studies are very frequently reported as cause and effect. I can understand why – Walking ‘cuts breast cancer risk’ Has more of a ring to it than Walking is associated with a reduced risk of breast cancer. The problem is that the more catchy headline is misleading, and it is left to the reader to spot the error.

Problem 2: what do we mean by a reduction in risk?

The second pitfall when it comes to knowing what to make of a study like this is more serious – and more troubling, because the fault lies not with mainstream journalists trying to enhance their stories, but researchers and journal editors being guilty of the same. The problem is this: as is so often the case, the results have been presented in terms of a reduction in relative rather than absolute risk.

The trial demonstrated a 14% Relative Risk Reduction (RRR) – but is that a 14% reduction of a big number or a small number? If the Dragons in Dragons’ Den are offered a 14% share in company profit, they are very quick to ask how big that profit will be before they part with their money. The same should apply to us before we invest our energies in a health intervention. If the Dragons want to know the absolute amount of money they can expect to receive then we should expect to know the Absolute Risk Reduction (ARR) of any intervention.

The problem is that ARRs are always a lot smaller than RRRs, and so they make research look far less impressive, and researchers are reluctant to give them the attention they deserve. From the BBC article it is impossible to find the ARR, and so you have to go to the original research – and even here only the abstract is available without paying a fee and so you have to work the numbers out for yourself. It turns out that the risk of developing breast cancer over the 17 years of the study was 6.4 percent, making a 14% RRR equate to a 0.9% ARR.

Let us assume for the moment that the reduction in risk really is due to walking. Then if you are a woman after the menopause, and you walk for 7 hours a week rather than 3, then over a 17 year period you would reduce your risk of getting breast cancer by 0.9%. Put another way, if 1000 women walked the extra 4 hours a week for 17 years that would be 3 560 000 hours of walking to save 9 cases of breast cancer, or 393 000 hours of walking per case. At 3 miles per hour, it’s the equivalent of walking more than 47 times round the world! Now I do know that this statistic is probably as meaningless as being given a 14% relative risk reduction – but it was fun to work out!

That’s not to say that walking is a bad idea – there are clearly very good reasons for walking more. However, whatever the associated health benefits might be, the two most compelling reasons to walk will always be these: it’s a very useful way of getting from A to B, and most people find they rather enjoy it!