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.

 

Combined Oral Contraceptives: Old Scare, New Data

I vaguely remember the pill scare of 1995; acres of media coverage, scary headlines and confused messages – I recall thousands of women stopping their contraception overnight for fear of a clot forming by morning, and scores of unplanned pregnancies as a result – but then maybe the way the statistics from the fallout were reported was as unreliable as the reporting of the science behind the original story. I was working as a junior doctor on a medical ward at the time; I didn’t need to think that much about contraception which might account for why my memory is hazy.

There was another pill scare this weekend, and I’m glad to say that there wasn’t too much media hysteria this time, but the story is still important and it will have caused many women to double-check their pill against the list in the newspaper – some will have been relieved to find their chosen brand to be in the clear, and other will be wondering what it means for them. The Mail, of course, couldn’t resist using the word Deadly’ in its headline, and relished the idea of ‘Every GP in Britain’ being told to do something, but the print of the article was reasonably measured, perhaps reflecting the fact that this is not a new story; far from it, there was no new research here, just an updated review of what we learned back in 1995 and some slightly adjusted figures.

It’s not bad to be reminded, though, that the contraceptive pill, like every other medicine we ever prescribe, is not entirely risk-free, and that both the risks and benefits of the pill do vary slightly with the brand. The review, by the European Medicines Agency, looked at the risk of blood clots, both in veins (Deep Vein Thrombosis or DVT and Pulmonary Embolism or PE) and arteries (stroke), which are two of the biggest safety concerns associated with the combined pill.

The first thing to say is that the risk of a clot is only increased with combined pills that contain oestrogen and progesterone (usually taken for 21 days followed by a 7 day gap), and that there is no risk of clots associated with the mini-pill, which contains progesterone only (eg Micronor, Cerazette or Cerelle) and are usually taken daily without a break.

We have known for a long time that the combined pills increased the risk of DVT, but what was new information in 1995, and caused the scare, was that the risk was different with different pills. At that time evidence emerged that older pills, like Microgynon, were safer than the newer pills, like Marvelon. Most women found that the older versions suited them just fine, but some women felt better on the newer pills – perhaps their skin was in better condition, or they had less PMT – and so these had become quite popular. What ensued nearly 20 years ago was a rather panicked move away from these pills, before the pendulum reset itself as people realised that the increased risk was not that great, and having good skin or not turning into a growling  bear on a monthly basis was actually quite important.

More recently there have been newer pills still – Yasmin being the most notable example – that promised to suit women even better than the older ‘new’ pills. There is no doubt that doctors and patients have been swayed a little by the idea that these pills are somehow ‘more feminine’, when actually most women feel no inhibition to their sense of womanhood on the tried and tested varieties, and the newest pills also seem to carry the slightly higher risk of DVT.

So what are the risks? Well the important thing here is to pay most attention to the absolute risk linked with each pill, and for each woman to ask if that is a risk she is prepared to take in order to find a reliable contraception that suits her. The headlines often quote the relative risk – ‘They are believed to double the risk compared to older varieties’  is more eye-catching than ‘About 1 in a 1000 women will develop a DVT’. While comparing the risk between different pills is important in deciding which pill to try, once you have decided which pill to use the fact that there might be a less risky pill out there becomes an irrelevance – what matters is whether you are comfortable with the level of risk attached to the pill you are taking.

The EMA review, therefore, is a useful reminder that no woman should start the combined pill without a discussion with her doctor about the risk of DVT, and that we should always start with the lowest risk pill unless there is a very good reason not to. It is also instructive to look at the estimates of risk given in this new review, as they are higher across the board (even for women who are not on the pill) than the estimates currently provided in the British National Formulary that most GPs in the UK will be using. I have tabulated the figures below for comparison – and I shall now be converting to the EMA figures, since I would always rather over-estimate a risk like this than under-estimate it.

 

The worst risk, therefore, is 120 per 100,000 – which is not insignificant, although it is worth remembering that this still means that 99,880 women out of every 100,000 on the highest risk pills will not get a DVT. The risk will also be lower if you have no risk factors – such as a family history of DVT/PE, smoking or being significantly overweight. When a DVT does occur it is usually in the first year – which supports the fact that if you are already well established on one of these pills there is no need to panic, and certainly no reason to stop the pill without first speaking to your doctor.

A final note about arterial clots (stroke); this was also reviewed in the EMA report, and although they did not report on the absolute risk other than it being low, it was reassuring that there was no difference in the rate of arterial problems between the different pills.

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!

Whooping Cough Vaccination for Pregnant Women: Neat Idea, Missed Opportunity

New medical advice is transmitted at such lightning speed these days that GPs and their patients often have to work their way through it in tandem. This was illustrated to me quite starkly on Friday morning with the announcement of a new, temporary vaccination programme in the UK for pregnant women to protect their children from whopping cough. The first I heard about the proposal was on the radio over breakfast, by mid-morning I learnt that all GPs had been sent an e-mail with the new instructions, and before lunch I was trying my best to advise one of my pregnant patients on the issue. Funny how you can feel reasonably up-to-date on Thursday evening, and behind the times only 12 hours later!

Having had the luxury of the weekend to actually read the information from the Department of Health I feel a little more prepared to advise women in the coming week – and this is what is required of a GP these days. It is not sufficient simply to adhere to the Government line on these matters; patients expect, and deserve, a doctor who will consider medical advice carefully and be willing to give thoughtful guidance. And my conclusions? In a nutshell, it’s a great idea, but why, oh why, oh why are the Department of Health not conducting a proper clinical trial?

The proposal is to vaccinate all pregnant women between 28 and 38 weeks gestation against Pertussis (whooping cough) as a temporary programme in response to the significant rise in infection rates in the last 2 years. And whatever else we think, it is certainly a neat idea. We do have a problem with Pertussis at the moment, both in the UK and worldwide. The number of confirmed cases so far in the UK in 2012 is nearly 5000, compared with around 1000 for the whole of 2011. There is no doubt that this is in part due to greater awareness of Pertussis at the moment on the part of doctors (myself included) and so increased diagnosis of cases in adults that would previously have been missed. However, this seems to be more than just an artefact, since there has been a sharp rise in the number of cases in infants under the age of 3 months, many of whom become very unwell and in whom diagnosis will always have been much more accurate. It is the very young who are the concern with Pertussis, since they will not yet have immunity from the vaccination programme, and their small lungs are especially vulnerable. So far in 2012 there have been 9 deaths in babies in the UK, and many more will have been seriously unwell.

How best to protect these babies? Well if everyone was immunised then there would be no-one to transmit the infection to them (the protection afforded by herd immunity), but this is extremely difficult with Pertussis since the protection afforded by vaccination wanes within a few years. Unlike the recent measles epidemics where poor uptake of MMR is clearly to blame, most cases of Pertussis in older children and adults occur in people who have been fully vaccinated. A programme where everyone was immunised every 5-10 years would work, but the cost of this would be enormous.

The beauty of vaccinating pregnant women is that we know the woman will make antibodies against the disease, and that these can cross the placenta in late pregnancy, be taken up by the baby and could afford protection in those crucial early weeks until the childhood vaccinations have kicked in. A single vaccine therefore protects exactly the at risk individual, and there is no need to depend on herd immunity. When a mother chooses to accept the vaccine she is choosing to protect her own child – the personal potential benefit is very clear.

We have good reason to think the vaccine is safe. It is a killed vaccine, which means it cannot possibly cause active infection, and these vaccines have reliably been shown to be safe in pregnancy. The vaccine also contains diphtheria, Tetanus and Polio vaccination (there is no single Pertussis vaccine so the combination has to be used) and the first two of these have often been used in pregnant women without difficulty. While there is not much data for this exact vaccine it seems extremely unlikely that there are any risks other than local reactions in the arm and very rare allergic reactions, and only vaccine conspiracy theorists are likely to argue against this.

It is also likely to work. I agree with the conclusions of the expert committee that:

…it is reasonable to assume that this approach would provide young infants with some important, although possibly not complete, protection against pertussis, and it is likely to be the most effective immunisation strategy to provide protection to young infants.

The report also state, however, that

the effectiveness of prenatal immunisation against pertussis to protect young infants is uncertain.

There are reasons to think it might not work. Will the maternal antibodies be sufficient to truly protect? Is there any risk that the antibodies might actually interfere with the response to the infant vaccination programme, and lead to reduced immunity later in childhood? So what should a scientist do when he or she has a good hypothesis which is uncertain: Test the hypothesis with a trial. There is such an opportunity here to answer this question for both the current and future generations – we need to conduct a Government funded, blinded, randomised clinical trial. Instead of rolling out this temporary programme as a knee jerk reaction, pregnant women could be offered the chance to be in the trial. They would receive either the vaccine or a placebo injection, meaning adverse reactions in the pregnancy could be compared, as could infection rates and outcomes in the babies.

Within a year we would start to get a real answer to this question. If it works then this could become a permanent and valuable addition to our fight against this serious disease. If it is shown to be ineffective then we could stop wasting time and money, go back to the drawing board and look for a better solution. What is more, the vaccine itself would be protected against unfounded claims of harm. Sadly the background rate of stillbirth is sufficiently high so that the Daily Mail headline “Whooping Cough Vaccine Killed my Baby” might as well have already been written, and without the robust clinical evidence available from a randomised trial these inevitable anecdotal stories will be much harder to evaluate. Granted, the trial would need to be large and the cost would not be insignificant, but the long-term gain of truly knowing how to protect babies from this infection must surely be worth it.

So how should I advise my patients in the lack of proper trial data – well it is a shame we shall never know for sure, but the issue is important enough to take action, and the balance of risk has to be in favour of the vaccine.

Miscarriage and Stillbirth – a Chance to Say Goodbye

There are so many good people out there, doing excellent things in our society, that it is rare to find someone engaged in something truly unique – but every so often you do come across a person, or an organisation, that has started something new and is meeting a need in society that has previously been ignored. Usually this comes about because someone has found themselves to be in need, looked around and found nothing out there – at which point most of us complain for a bit, suggest someone should do something, and then get on with our lives. When that person is full of drive, energy and determination, however, they might just rise to the challenge, fill the void and come up with something special.

Zoe and Andy Clark-Coates are just such people, and have turned the personal tragedy of recurrent miscarriage into a remarkable charity called Saying Goodbye. They have kept their remit simple, with their aim being to arrange remembrance services for couples who have lost a baby either in pregnancy or early years, but are not short of ambition – the services are held nationally, and in some of the grandest cathedrals in the land.

There is no shortage of testimony from couples who have found these services hugely beneficial as they come to terms with their own bereavement, and it is interesting to consider why there might be such a need for these shared experiences of grief. In part, I am sure it is because of the success of modern medicine. The death of a child is such a rare event in Western society nowadays – a cause for celebration for society as a whole, but a source of isolation for those who do still suffer the tragedy of losing a child. In times gone by the grief felt by those who lost a child would have been no less acute, but they would have been surrounded by family and neighbours who understood and who could share their pain. The services organised by Saying Goodbye hope to give people the opportunity:

‘To just stand in a room with hundreds of other people who have all been through a similar experience, knowing everyone is there to support one another, will be such a powerful moment, and we hope it will be life changing to many

Another, perhaps more complex, reason why these services will be significant is the uncertain status of miscarriage in our society. There is no ambivalence surrounding stillbirth – women suffering from this much rarer event are afforded the full legal and emotional status of one suffering a major bereavement, and few would argue that it is not a more significant trauma than a miscarriage in the first three months of pregnancy – but where does that leave those who do suffer miscarriage? Are they allowed to grieve? Their loss is afforded no legal status – there is no death certificate and no burial – the child they have lost is often euphemistically referred to as “the products of conception”, and society frequently expects a rapid return to normal life. Early pregnancy has an ambivalent status in our culture, as we struggle to hold two contrasting values. On the one hand we do try to acknowledge the weight of loss suffered in a miscarriage, while on the other we place a high value on the freedom of choice when it comes to the decision to continue with a pregnancy and the role of termination. There is an inherent tension between these two positions which society is unlikely to resolve, and I suspect it is easier for our collective conscience if it is miscarriage that loses out. Services of legitimised remembrance in the awe-inspiring setting of a cathedral may help to redress this imbalance.

The services are open to people of any faith, or no faith at all, and the intention is to be as inclusive as possible. They won’t be for everyone – people are naturally resilient, and when sorrow occurs most of us find our own way to come to terms with what has happened. For many couples who lose a baby in pregnancy they will have worked their own way through their grief and will not feel a need to revisit their loss. One thing I have learnt about grief, however, is that there is a danger in both too much grieving and too little – and that the ‘right’ amount of grieving is different for every person. Too little opportunity to grieve shackles us to the past and we are afraid to move on for fear of leaving some of ourself behind, while if we focus too much on the process of bereavement we may forget that we have both a present and a future. For those who are on the painful journey of bereavement there are no easy answers and no shortcuts, but for some the services organised by Saying Goodbye may provide some life-giving refreshment along the way.

To find out more about Saying Goodbye, visit their website: www.sayinggoodbye.org, or follow them on Twitter: @SayingGoodbyeUK

Who’s Afraid of the Big Bad C?

There is a numbers game called 21, where two players count up in steps of 1, 2 or 3 with each trying to force the other to call the number 21 – I hear that sometimes drinking is involved. Doctors and their patients often play a similar game, only with words rather than numbers, and without the usual inebriation.

A typical opening gambit from the patient might be: “I’m sure it’s nothing to worry about, doctor,” which is a gentle thrust easily countered by: “Is there anything you are concerned it could be?” This usually finds its mark and the doctor is home and dry, but a determined patient might stubbornly pass the baton once more like this: “Do you think it’s serious, doctor?”, and the physician is undone – the C word must now be used. Not the vulgar C word that might excite a Censorship Board, but the genuinely offensive version that we are truly afraid of. The C word that has the power to turn our world upside-down: Cancer – because it’s always cancer that lurks in the background of these conversations.

I am sure there are individuals who can take it in their stride, but there is no doubt that as a society we are terrified of cancer, and will go to remarkable lengths to try to avoid it. And rightly so, it kills people – we should indeed see it as our enemy and combat it wherever we can – but what is it that gives cancer such a unique status in our society? After all, it is not the only condition associated with significant mortality.

The extraordinary potential for cancer to impact a person’s life was powerfully described by Emma Gilbey Keller in her article for The Guardian on 27th April, as she eloquently detailed her own 40 day journey with the disease – from first detection of abnormal cells by mammography, through bilateral mastectomy, ITU, infection and eventual recovery. Harrowing. Her own word, and the only one that is suitable. Anyone involved in health care should read her article and then have some time alone to think. It certainly got me thinking.

If the only thing that is bad about cancer is that it kills people, then I should be delighted for her – she certainly won’t die from breast cancer now. Her oncologist was clearly pleased – pronouncing the all clear 5 days after the operation, another triumph, another life saved. So why did the article leave me feeling sickened and angry at the doctors who did this to her? Maybe there is much more to cancer than death – and is death inevitable anyway? Emma Gilbey Keller’s cancer was detected by screening and was the earliest type of breast cancer, known as Ductal Carcinoma In Situ, or DCIS. Under the microscope DCIS looks like cancer, and so doctors have given it this exalted title, but in real life it is disingenuous to brand it that way. When I hear the word cancer I think of something that will inevitably spread and kill if left untreated. DCIS is more likely to go away on its own as our immune system sorts it out. Estimates are difficult, but between 14% and 53% are thought to develop into an invasive cancer over a period of 10 years. The problem is that the treatment for DCIS is largely the same as for a true cancer – surgery and radiotherapy.

The day you are told you have cancer is likely to burn its way into your memory with the clarity usually reserved for your wedding, the birth of your child or a national disaster like 9/11. So what would I fear if I were to be diagnosed? Death, yes, but far more than that. Loss of control would be top of my list. Knowing that life was suddenly put on hold – whatever I had planned for the next however many weeks will have to be shelved. And the expectation for this is high – doctors get very annoyed if you suggest delaying treatment until after your holiday, or some important deadline at work. Cancel everything, they will demand, your life is at stake.

Then there is telling everyone – and the inevitable talk that will follow. Well meant, I’m sure, but can I bear the idea of people saying: “Have you heard?” and “He’s being so brave.” How do you tell people? Will they know what to say to me? Do I want this label? Do I have a choice?

Finally there is the treatment. Surgery – that’s going to hurt! And not surgery that will give you something in return, a new lease of life like a cataract operation or a new hip. Surgery for a breast cancer, or a prostate cancer picked up on screening will not make you feel any better – you weren’t feeling ill in the first place. And radiotherapy, chemotherapy, whatever they suggest – side effects, nausea, tiredness, depression, the list goes on. Risks carried with every part of it, but eclipsed by the drive to get rid of this thing that I can’t even see. Emma Gilbey Keller said risk was the reason she had to do it – she couldn’t take the risk of doing nothing. I don’t blame her for one moment, but when you think about the risks she did take in order to eliminate that one risk; the definite, palpable pain she went through in order to prevent something that might, or might not, happen sometime in the future; the permanent changes to her body (remodelling, her plastic surgeon arrogantly called it)…well it certainly gets you thinking.

The biggest harm associated with cancer screening is the fact that there will inevitably be some people who are treated needlessly, as their ‘cancer’ will never actually make them ill. When the only treatment doctors can offer them is as aggressive as it is for cancers like breast or prostate cancer, the medical profession needs to acknowledge that in trying to cure someone of this disease, it will inflict on them much of the pain and misery associated with the very condition it is trying to prevent. And when doctors dare to use a word as powerful and emotive as the Big C, they must be very careful that they are not coercing people to look for cancers that no-one knows how to treat – and very cautious if radical treatment is the only option they have to offer if they find something.

PIP Breast Implants – Where is the meaning behind the statistics?

The controversy over the PIP Breast Implant Scare all seems to come down to the  rate of rupture of these suspect devices – believe the French figure of 5% and you may agree with the French Government that all the implants should be removed. However, if you side with the statistics of the English Government and the Medicines and Healthcare products Regulatory Authority (the MHRA, the UK body that approves or otherwise the licence for medicines and surgical devices), and you may find the 1% rupture rate they quote rather more reassuring, and agree that there is no cause for alarm. If it offends your European sensibilities to decide which side of the channel should win your allegiance, then you can always opt for the 7% figure quoted by the Transform cosmetic surgery group – although as this was only 7 out of 108 patients this is hardly the most robust of statistics.

For my own part, I have a major problem with all these numbers, which is this: What do they mean by a rupture rate? Is the quoted rupture rate the rate of rupture in the lifetime of the implant or the rate per year? There is a very great difference between the two! 5% over the lifetime of an implant might be very acceptable to some women, but I suspect few would be unconcerned about a 5% risk year-on-year.

In the last 2 weeks I have made several attempts to scour the internet and try to find clarification on this matter. I have reviewed the guidance on the MHRA website, and trawled through numerous news reports from the BBC, Reuters and other respected news agencies; I have searched Google Scholar and done my best to review the literature (distinctly lacking as much of the important data is held by the companies themselves or the surgeons performing the operations and has not been published in journals). I have read the letters to Health Care Professionals from the Chief Executive of the NHS and the Chief Medical Officer. In all, I have probably spent 2 or 3 hours in the cause, and – until today when the first glimmer of clarity has come my way – I have found nothing: No clarity on what is meant by the rupture rate, and no reference for the original figure that these data are based upon. If it is this hard for a GP to find answers, how must it be for a worried patient, who may have no medical training, to make the important decision as to whether or not to subject herself to an operation on the basis of an uncertain and undefined risk?

And the glimmer of clarity? Well the Department of Health published its interim report yesterday. It is a typically meaty Government document and so not for the faint hearted, but it does contain the following point (page 8, paragraph 18):

“Much attention so far has been given to the issue of rupture in breast implants. The cumulative risk of rupture of a breast implant increases progressively over time. An analysis published by the FDA showed that the rupture rate for the Allergan implant is 0.5% after 2 years, rising to 10.1% (cumulative) after 10 years. For Mentor implants, the post implantation failure rate at 8 years was 13.6% (cumulative). It follows that quoting a “rate of rupture” for an implant, without specifying the time since the original implant, is unhelpful and  potentially misleading (my italics). ”

Thank you Department of Health! So the 1% rate (relating to a different implant that has no safety concerns) rises to 10% over 10 years – in other words it is 1% per year. Interestingly the 7% rate quoted by the Transform cosmetic group was 7 patients out of 108 who had had implants since 2005, so presumably this is 7% over 6 years, which sounds suspiciously close to 1% per year to me, even though it was reported by the media as being higher even than the 5% French rate – which still remains totally unclarified.

The baseline rate, therefore, that any woman should have had explained to her prior to surgery and against which the PIP data needs to be compared, is a 1% year-on-year rupture rate. Unfortunately, when the group analysing the data for the DOH report came to the PIP implants (included in a very confusing Annex D in their report) they found that the data was woefully incomplete and that no conclusions can be drawn. For the moment there is not enough evidence to recommend routine removal on the basis of the risk of rupture, but they do conclude that it could be warranted on the grounds of the anxiety that the implant scare has caused, and that private clinics should be prepared to pay for this.

A significant concern about the way this controversy has been handled is the assumption that has often been made that the only thing the patient needs is guidance from the authorities – that all that is required is for the Government, be it English or French, to issue a recommendation that all the affected women should follow. It is certainly helpful for Governments to issue advice where they can, and many women will indeed want to follow it, but many will want to decide for themselves. Whether or not to have the implants removed will be a very personal decision, and women will need to be able to come to this individually. For this they need a clear presentation of the risk, with numbers that actually mean something and in a form that can be easily understood.

Cervical Cancer Vaccine – warts and all

Warts don’t make headline news. They never have, and they never will. And so when the Government announced a change in the cervical cancer vaccine available on the NHS, to a vaccine that also protects against genital warts, it was never going to make the front page – or if it did, I certainly missed it.

I caught up with the change via the medical press, and an announcement sent to all GPs from the Department of Health, but was comforted to see that the ever-reliable Fergus Walsh managed to find space for it on the BBC News website. In case you missed it, I thought I would air it here.

The issue relates to a previous article I have written in this blog where the issues are discussed in more detail. In brief, there are two vaccines that are equally effective in their protection against cervical cancer Cervarix and Gardasil. The only real differences between them are that Gardasil is more expensive (hence not an initial favourite with our limited NHS resources) and also gives protection against the two strains of Human Papilloma Virus (HPV) that do not have any link with cancer, but cause the majority of genital warts. The Government has redone its calculations, and been advised by the Health Protection Agency that the cost saving in terms of the reduced cost of treating genital warts makes the more expensive vaccine better value for money after all. The change will happen in September 2012.

If you have read my previous article, you will know that I am quite ambivalent with regard any merit of one vaccine over the other,  and the purpose of this article is to try to allay the natural fears that may arise in any young woman, or her parents, who are being told that the vaccine they received is to be replaced by a ‘better’ one. I am glad to say that if you want to protect against cervical cancer then you don’t need to worry one jot: The current vaccine is as good as anything at preventing the HPV strains that are associated with cancer. Sure, you might have liked to be protected against warts – it has a sort of Buy-One-Get-One-Free appeal to it after all – but at best this is a useful by-product of a vaccine designed for an altogether different purpose, and at worst a clever bit of marketing by Sanofi Pasteur MSD who, like any good salesperson, have managed to convince us to buy an upgrade that we didn’t know we needed.

At the end of the day, if you are concerned about genital warts your best protection is always going to be a responsible attitude towards sex, and a condom – with the real BOGOF bonus of protecting against something really important – like HIV…Hepatitis B…Herpes…unwanted pregnancy…Chlamydia…

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.

Breast Cancer Screening – time for an honest presentation of the facts, and to let women decide for themselves.

With ironic timing, the notification that our area was next in line for the national breast screening programme arrived on the same morning that the BBC ran a major news item announcing that the programme itself is going to be reviewed, because it is not clear whether screening is such a good idea. So women in our area face the unenviable prospect of being invited for their 3-yearly mammogram with an independent review having been announced, but long before we will know its outcome.

The review was announced by Prof Mike Richards, and is certainly overdue. There has been a controversy brewing in this area for several years, and the trigger for the announcement was an open letter in The British Medical Journal by Prof Susan Bewley, a Professor of Obstetrics who came into the debate as a well-informed patient rather than an expert in the field of breast cancer. She neatly summarises the two major concerns: The balance of benefits against harms, and the way information about the screening programme is delivered to women who are invited to take part in screening.

When the programme was introduced in the late 1980’s there was a great deal of interest in the potential harms of screening, but these focused on the risk of repeated radiation exposure from 3-yearly mammograms and the question of whether or not this would cause new cases of cancer. Once this risk had been established as being very low (which it is) and the benefit that breast cancer screening saves lives (which it does), there was a clear green light for screening, and a widespread belief that it was an unquestionably good thing. Two things have changed since then. The first is that the treatment for breast cancer has vastly improved in the intervening years (particularly with the arrival of hormonal treatments like tamoxifen which can treat the cancer wherever it lies in the body) – if the outcome for treating more advanced breast cancer improves, then the benefits of finding it early by screening will decrease. The second thing to have changed is that there is a growing understanding within the medical community that the greatest potential harm of any screening programme is not the screening process itself, but the possibility of unnecessary treatment that may result.

The story on the BBC news last week included an interview with a woman who had just had treatment for a tumour detected by screening. She reported that she was glad to have been screened, as if this had not been done then she ‘would still have cancer cells in her body’. This is a very understandable conclusion, but it does not take account of the fact that most of us have some cancer cells in our body most of the time. Cells are always transforming into tumour cells, and our immune system is remarkably efficient at clearing them up. Some of these cells will multiply into what looks like cancer under a microscope, but will either grow so slowly as to never be a problem in our lifetime, or will shrink away in time as our immune system gets to grips with them. When we say that someone has ‘got cancer’ we usually mean that they have developed symptoms from a cancerous growth that is making them unwell – a cancer that has evaded our immune system enough to cause disease. What, then, should we conclude when we find cancer cells by screening, which have not yet caused any symptoms? Is this is a cancer that is going to ‘break through’ our immunity with potentially fatal consequences, or is it one that is going to disappear? Did the woman in the news article have cancer with a ‘Big C’, or not?

The problem is that there is no way of telling, and cancer is such a serious diagnosis that the only approach you can take once you have found cancer cells is to treat every case you find – in this case that would usually mean surgery (a lumpectomy or mastectomy) followed by radiotherapy and hormone treatment. The biggest harm of screening, therefore, is the potential to inflict all this treatment on a woman who would never have needed it. There is a general acknowledgement that these unnecessary treatments occur, but a wide disparity in how often this is likely to be. The two most widely quoted statistics on the subject are from a paper by Duffy et al and a Cochrane Review on the subject. The former estimates that up to two and a half lives are saved through screening for every unnecessary treatment, while the latter concluded that for every life saved there are ten women subjected to unnecessary treatment – that is a twenty-five fold difference! For my money, I am inclined towards the Cochrane Review. It is a much larger analysis which incorporated the Swedish study (conducted by Duffy and his colleagues) that formed the backbone of the other paper, and has been performed by an organisation that places a major emphasis on proper scientific scrutiny of the evidence and elimination of bias.

The way information about the screening programme has been presented has also been much criticised. The 2009 NHS leaflet (which it still the leaflet that you get to if you search on the NHS Choices website) made a minor reference to the possibility that a false alarm might cause worry, but  no other comment on potential harms and no suggestion at all that over-treatment is a possibility. After criticism of this document, the 2011 Leaflet now has a section on harms, and the following comment on over-treatment: ‘Screening can find cancers which are treated but which may not otherwise have been found during your lifetime.’ This is an improvement, but remains vague and there are no statistics to help a woman know the likelihood of over-treatment. It has also been criticised for making misleading statements, such as: ‘If a breast cancer is found early, you are less likely to have a mastectomy (your breast removed) or chemotherapy.’ While this is true, it fails to mention the fact that women who are screened for breast cancer are about 20% more likely to have a mastectomy than those who are not screened – because they are more likely to be diagnosed with cancer, and so to have treatment (Cochrane Review ).

The authors of the Cochrane Review were so concerned that patient leaflets were one-sided in their promotion of screening that they have produced an alternative leaflet, which aims to be more balanced. Surely this is the way forward. It is the Government’s job to decide if, as a nation, we can justify providing a screening programme, but that programme should not then feel the need to urge women to take up the invitation to be screened – it should simply present the facts as clearly as possible and let women decide for themselves.

If you want them, these are probably the most reliable statistics available at the moment:

If 2000 women are screened regularly for 10 years, then one of these women will benefit, as she will avoid dying from breast cancer; 10 women will receive unnecessary treatment for cancer; and 200 women will experience the psychological strain of a false alarm.