Some things in life you might prefer not to know. That your surgery for, say, prostate cancer has left you incontinent but the disease would never have bothered you. That the mastectomy you had wasn’t actually necessary. That you’ve been taking hypertensive drugs for 20 years, but you were never going to have a stroke and your blood pressure wasn’t that high after all. If you are one of these people, you are what is known as over-diagnosed. It may – or may not – be some consolation that you’ll never know whether you are one of them.
The over-diagnosed have always been among us, although they haven’t tended to get much attention, generally having been overshadowed by the under-diagnosed and the misdiagnosed. Increasingly, however, researchers are calling attention to medicine’s ability to not only treat the sick but also harm the perfectly healthy. Caring, it turns out, can be dangerous.
“There’s a growing amount of evidence being published in the world’s top medical journals suggesting that many, many people are being over-diagnosed, given labels and diagnoses that they may not need, and as a result receiving treatments that might do them more harm than good,” says Ray Moynihan, author and senior research fellow at Melbourne’s Bond University, who is doing a PhD on over-diagnosis.
Moynihan, in New Zealand recently to speak at a Cochrane Collaboration conference, is the lead author of an article published in the British Medical Journal earlier this year, in which he and his co-authors identified a number of studies showing compelling evidence that when it comes to medical care, we can get too much of a good thing. Diseases for which there is evidence of over-diagnosis include breast cancer, thyroid cancer, prostate cancer, lung cancer, high blood pressure, high cholesterol, malaria and attention deficit hyperactivity disorder (ADHD).
In the US, the expanded definition of chronic kidney condition has led to one in 10 people being classified as having it; one study estimated up to a third of people over 65 meet the new criteria but only one in 1000 of them will develop end-stage kidney disease in a year. A large Canadian study suggests almost a third of those diagnosed with asthma may not actually have the condition. Moynihan and his co-authors also cite research that shows cancer detected by prostate-specific antigen (PSA, a marker for prostate cancer found in the blood) could be over-diagnosed by more than 60%. “Over-diagnosis poses a significant threat to human health.”
What exactly is over-diagnosis? Moynihan gives two definitions for over-diagnosis. Strictly, it refers to a medical intervention in which healthy people without symptoms are diagnosed with and treated for early signs of a disease that wouldn’t have gone on to hurt them – for example, a cancer that could only have been detected through screening but would not have affected the person’s health.
More broadly, it refers to a growing dependence on medical intervention, in which healthy people with a borderline problem – such as hypertension, high cholesterol or pulmonary embolism – are treated as if they are sick. “Give a child a label of ADHD and you will have affected that child’s personal narrative forever,” says Moynihan. “You have fundamentally changed that person’s perception of themselves.”
Over-diagnosis is a difficult concept to grasp – it’s counter-intuitive to think your GP or health specialist could be too cautious. It’s also hard to quantify. That it exists is often only discovered through statistical analysis and population modelling, such as studies that compare the incidence of cancer among a screened population over a period of time to that of an unscreened population; if there is more cancer in the screened population, the difference can be put down to over-diagnosis.
At an individual level, it’s impossible to tell who is over-diagnosed. If you’re told you have a little bit of cancer but nobody knows if will become invasive, you’re likely to get it cut out – and you’ll never know if you were treated for nothing. If you take hypertensive drugs for 20 years and don’t have a stroke, you’ll never know whether that was because of the drugs or you weren’t going to have one anyway.
But although we can’t identify who the over-diagnosed are, nobody doubts they exist. That they are being taken more seriously was apparent in October, after an independent panel in the UK reported its findings on the benefits and harms of breast cancer screening. The panel concluded that breast cancer screening saves about 1300 lives a year – but also about 4000 women a year are treated for a cancer that wouldn’t have affected their health. The panel concluded it was imperative the medical profession be more upfront about this.
Too keen to screen?
Breast cancer screening is under the spotlight as experts weigh up the harm it can cause vs the lives it can save.
National breast-screening programmes would not have been introduced in countries all over the world without sound evidence that doing so would save a significant number of lives, and that the benefits outweighed the potential harms. However, in recent years, a number of studies have challenged this evidence. Last month, the New England Journal of Medicine published the results of research that estimated breast cancer has been over-diagnosed – that is, tumours have been detected that would never have led to clinical symptoms – in 1.3 million women in the US in the past 30 years. It also says that in 2008, breast cancer was over-diagnosed in almost a third of all diagnosed breast cancers.
A long-standing and vociferous critic of breast cancer screening and the director of the independent Nordic Cochrane Collaboration, Peter Gøtzsche has studied the data for more than a decade. He believes that for around 2000 women screened, one life is saved and 10 women are harmed through over-diagnosis. But other epidemiologists looking at much the same data have come up with very different results. According to a study by the European Working Group published this year, 14 to 18 lives are saved for every 2000 women screened biannually for 20 years, and eight cases are over-diagnosed.
THE MOST AUTHORITATIVE FINDINGS
Perhaps the most authoritative findings, however, were published in the Lancet in October – the results of an independent panel commissioned by the national cancer director for England and Cancer Research UK. The panel, set up to find some objective clarity for this controversial issue, was composed of eminent experts in medical epidemiology, statistics, breast cancer diagnosis and treatments, as well as a patient advocate. The panel examined the data from 11 randomised trials, and also reviewed the published evidence and submissions from experts involved in the debate.
The panel’s conclusion was that breast cancer screening does save lives – about 1300 women in the UK each year. However, it also concluded that about 4000 women are over-diagnosed each year. The panel made it clear that over-diagnosis isn’t misdiagnosis, and doesn’t refer to the anxiety of going for a mammogram or for some of the more invasive procedures that can follow an abnormal one. They were referring to treatment for breast cancer, found through screening, that might never have affected the woman’s health. Treatment typically involved surgery, radiotherapy and drugs, which all take a psychological and physical toll.
The panel acknowledged that their review depended on trials done over two decades ago, and the results were therefore imperfect. But these days it would be unethical to do a trial in which half the participants aren’t screened, as it’s widely accepted that screening saves lives. The panel recommended women still get regular mammograms, but also that women needed to be better informed about the potential harm of breast screening when they were invited to participate in the national screening programme. As a result, the National Health Service plans to revise its information brochures.
BreastScreen Aotearoa is planning to do the same. “We were already looking at revising our pamphlets, because there has been so much discussion about this over the past year or two,” says the organisation’s clinical leader, breast physician Dr Marli Gregory. “Women are asking questions … so we are going to have to tell them that if they are diagnosed, there is a small possibility that we have found a cancer that would not shorten their life.” She notes the UK panel put the chance of that at 1%.
TO TREAT OR NOT TO TREAT?
Much breast cancer over-diagnosis is thought to involve ductal carcinoma in situ (DCIS), a lesion that can be detected by mammography, involves malignant cells but is confined to the tubes that move milk to the nipple. Doctors say they are getting better at distinguishing between those likely to turn into invasive cancers and those that aren’t, and are targeting treatment accordingly.
Also, notes Gregory, if women haven’t traditionally been told about over-diagnosis before their first mammogram, they would be told about any uncertainties once diagnosed. “We don’t believe intermediate and high-grade DCIS is over-diagnosed, because that has a high percentage of conversion to disease. It’s the low-grade, the slower-growing form [where it’s less certain] … but surgeons will say to women, ‘This is a form of breast cancer, they are cancer cells, but it is a form that may never progress, and unfortunately we can’t tell you whether this is the case.’”
The potentially over-diagnosed cases are those involving “tiny little clusters” that are more likely to be treated with a partial mastectomy and radiotherapy, she says. Treatment is unlikely to include chemotherapy. But some of these women still opt for a complete mastectomy. Others forgo all treatment and opt for more regular screening. The ideal solution, of course, is that scientists figure out how to distinguish between cancerous cells that carry a significant health risk and those that don’t. Until then, the message remains “screening saves lives”, but the virtues of screening are not as straightforward as we might think.
GRAPPLING WITH COMPLEX INFORMATION
Still, it doesn’t take an epidemiologist to understand the issue. This was highlighted in a study done by Dr Charlotte Paul, emeritus professor of preventive and social medicine at the University of Otago. In 2007, she set up a citizens’ jury of 11 women aged between 40 and 49 to consider the merits of breast cancer screening in their age group. This was after the Ministry of Health lowered the age of breast screening from 50 to 45, against scientific advice but under public pressure. The women heard from experts with different perspectives: a representative from the ministry, one from the Breast Cancer Foundation and an epidemiologist.
Initially, all the women supported lowering the age of screening, but it became apparent in the session that they had no idea screening could cause harm and also thought the benefits for this age group were greater than they were. After two days of briefing and deliberation, 10 out of 11 women changed their mind. Paul was “delighted” with the result, not so much because of their conclusion but because they were so engaged and capable of grappling with complex information, and once presented with the evidence were willing to come to a new conclusion. “We can’t replicate this process for everyone and every test, but it shows the power of good information and reasoned debate.”
Which is exactly what Moynihan has been saying. “While all of us feel that we don’t know how to accommodate this new information about over-diagnosis, it’s incumbent on us to do so … Uncertainty is not a reason not to communicate the information.”
WHAT’S CAUSING IT
Clinicians and GPs have generally welcomed his efforts to draw attention to over-diagnosis, says Moynihan. “It really strikes a chord. There is a huge amount of unease within the medical profession itself that too many people are being over-diagnosed unnecessarily.”
It also chimes with Dee Mangin, director of the University of Otago’s Primary Care Research Group, who identifies a number of forces driving over-diagnosis:
- an ageing population concerned about health;
- increasingly sophisticated medical technology;
- the commercial imperatives of both the pharmaceutical and diagnostic industries;
- the tendency to prescribe by numbers according to set (but shifting) guidelines; and
- the goodwill of physicians whose worst fear would be to miss the diagnosis that could have saved a patient’s life.
And then there’s the system. “The way that quality care is measured is by how much we do – what proportion of our patients are screened for ‘x’, or what proportion of our patients who have high blood pressure are on ‘y’,” says Mangin. “There’s no measure of the skill and quality of care involved in not doing things, but these are more complex decisions that require a lot more skill and judgment and knowledge.”
It takes nerve and experience not to intervene. “It’s like a U-shaped curve,” says Auckland-based GP Dr John Cameron. “When you first come out of medical school, you’re absolutely dangerous; you over-diagnose, you over investigate, you’ll send anyone to hospital. Then you get to the bottom of the curve, when you have the confidence to know what is going on, and you’re safe. Then you get older, and you start to believe that nothing will go wrong, so you start to overlook.”
He agrees with Mangin, that GPs are encouraged to prescribe by numbers, which can prioritise a disease over an individual. “We’ve got this disease called ‘red-letteritis’ – you get a lab result and it has a red letter beside it, which means it’s outside the normal range. But is this pertinent to a person’s health? Does it imply that there is something there besides a red letter? “As generalists, I’d hope that we raise ourselves above the level of the disease to the level of the person. Not just to look at what a disease is, but to say, ‘Is it important to this person that they have this problem? Is it even a problem?’”
Compounding the issue is a widespread but uninformed faith in screening – what Moynihan calls “our cultural love affair with early diagnosis” and the misplaced belief that finding something early will save us from a terminal illness. Sometimes early diagnosis saves lives, but having the technology to spot an abnormality doesn’t mean there’s an effective treatment for it. Moreover, while increasingly sophisticated imaging technologies can identify smaller and smaller abnormalities, doctors don’t necessarily know whether they are normal abnormalities or dangerous abnormalities.
“Medical imaging has become a real problem,” says Bruce Arroll, professor of general practice and primary healthcare at the University of Auckland, noting there’s even an acronym for it: Vomit, or victim of medical imaging technology. (There’s also Barf, for brainless application of radiological findings.) “You have an MRI scan and you’ll find all sorts of things in the body that wouldn’t normally bother you. Suddenly, you find all these things that you can do something about, so you give it a name and invent a procedure.”
But then new technology often has been problematic. Cameron recalls being a house surgeon three decades ago, when the hospital where he was working got a machine that offered what was known as a Smac (sequential multiple analysis by computer) test, which delivered results for tests that hadn’t been requested. “The rate of parathyroid tumours multiplied by about 40 times and so did the rate of surgery.
“When the routine testing was changed to look for serum calciums, we found these abnormal calcium [levels], which meant that more people were investigated for hyperpara thyroidism, more parathyroid adenomas were found and more people underwent surgery. So by installing a new machine, we found a new disease and put patients at risk … the bottom line is around whether or not this actually improved the health of the population. Not everyone with raised calciums actually needed surgery, especially if they were not symptomatic. But on finding a positive laboratory result, the clinicians were duty-bound to further investigate and then offer therapy.”
Like many GPs, Cameron once supported prostate cancer screening, but is far more circumspect about it now. He points to this year’s findings of the US Preventive Services Task Force, which looked at the scientific evidence and concluded that many men are harmed as a result of current methods of prostate cancer screening and few, if any, benefit. Until we get better screening methods – which can better distinguish between invasive cancer cells and those that won’t affect a man’s health – it recommends against screening.
Cameron tries to tell his patients about the pros and cons, but it’s tricky: how can what is known at a population level inform a personal choice? “Surgery for prostate cancer can cause real harm. But if your mate has been diagnosed with prostate cancer and had surgery, what is your wife going to say to you? ‘He’s been diagnosed, you could have it, you should go and get screened.’”
A PANDORA’S BOX OF PROBLEMS
In short, screening can open a Pandora’s box of problems we might have been better off not knowing about. “There’s the popular notion that if we just look hard enough, we should be able to prevent any disease, but the reality is quite different,” says Mangin. “There are selected areas where prevention and early detection are very effective, but they are quite limited.”
Which is why any programme that involves the screening of asymptomatic people across a population must be introduced with extreme caution, because of the potential to generate unnecessary anxiety, and also because it can lead to unnecessary treatment among large groups of people. “All medicines are poisons to an extent, but when you get to a certain point, the balance between the likely benefit and likely harm reaches a tipping point. The more unwell a person is, the more likely they are to have reached that point. But the earlier you come back in the disease process, the more likely the patient is going to be suffering harm without the real benefits.”
Mangin has a particular interest in polypharmacy, the over-medicalisation of healthy old age. “The average number of medicines an older person in New Zealand is taking is seven. Once you get beyond five, the chances of having an interaction between two of the drugs gets increasingly high. We’ve never been healthier or lived longer, but we’re blighting people’s healthy old age by loading them up with an enormous number of medications.”
In a recent study while working with an Israeli-based geriatrician, Mangin put the concept of “less is more” into practice, by weaning elderly patients off some of their medications. “What we found was that people’s quality of life improved. For several patients, their cognition, their mental state, improved substantially. And a significant proportion of the drugs didn’t have to be restarted, or were substantially reduced.”
Hers is an approach that focuses on the patient as a whole person, rather than as a collection of diseases or risk factors. Not treating the elderly for disease-risk can lead to accusations of ageism, but how many risks can we avoid at the end of a long life? “If you’re reducing your risk of cardiovascular death, then there’s quite a bit of evidence that it increases your risk of dying from cancer. We’re doing that without people’s informed consent. If we tell you that we’re reducing your chances of cardio vascular death by 12%, you’d naturally assume that your life would be better. But if you’re told that you’ll increase, by the same amount, your risk of dying from cancer, then people would often make quite different decisions about whether they take that drug or not.
“This is only one part of over-diagnosis, but with an ageing population and lots of co-morbidity, I think that what will define how well we provide medical care in the next decade will be how well we make the decisions not to treat and not to investigate.”
THE EBB AND FLOW OF MEDICAL PROGRESS
On the other hand, over-diagnosis could be a stage we just need to go through, and is often more easily identified in retrospect. “When you introduce a screening programme into a country, the incidence of the disease increases, because we’re finding things earlier, so things are going to look worse before they get better,” says GP Phyllida Cotton-Barker, who is on the Breast Cancer Foundation’s scientific advisory committee. “And so the harder you look, the more you’ll find.
“Then you set up a perpetuating disease register, and it’s then that you get an adequate population base within a country to be able to understand the disease itself. So by over-diagnosing, in inverted commas, you develop a cohort where you can then start to tease the disease out. And then in retrospect, you can say, ‘Okay, this group we should have left alone.’ And with new imaging techniques, we know we can leave a certain group alone.”
Of course, the danger is that not all clinicians have a strictly clinical response to new medical knowledge. “If you’ve just gone and bought a million-dollar screening machine, and then find it doesn’t do a certain job, you’ll want to keep selling it rather than aborting the technology. “But I think doctors in primary care have demonstrated a willingness to change their behaviour when new information comes forth.”
She mentions ear infections in children, for instance. “We’d been over-treating that with antibiotics, but then we found that if you treat 100 children, that might benefit eight of them and only reduce their ear pain by half a day. So we stopped.”
Perhaps this is the nature of medical progress: things ebb and flow between over-diagnosis and under-diagnosis. Many of the concerns about over-diagnosis have pointed towards the overuse of hypertensive drugs and statins, particularly in the UK and US. But New Zealand GPs have swung in the other direction, and are encouraged to look at blood pressure and cholesterol in the context of overall risk factors, such as age, gender, smoking history and weight – although some claim this is resulting in under-diagnosis.
In some ways, New Zealanders might be protected from over-diagnosis by fiscal constraints. “One of the issues of over-investigation and over-treatment, which is another way of expressing over-diagnosis, is that it will vary from condition to condition and from time to time, as the cost factors and our understanding of costs and benefits changes,” says Ian Reid, deputy dean of the University of Auckland’s Faculty of Medical and Health Sciences.
Reid led the game-changing research that found that taking calcium supplements for osteoporosis was associated with a higher risk of cardiovascular disease – and that while calcium supplements increased bone density, they didn’t reduce the risk of fracture. The question now is whether women in their fifties should start taking bisphosphonates, which reduce the loss of bone density – to avoid a fracture that may or may not occur in 10 or 20 years’ time – but which are not without side effects.
Some are arguing that osteoporosis will be the over-diagnosis story of the upcoming decades. Reid says this might be the case in North America, but is unlikely to happen here. “We’re not in a position to be spraying these drugs around. Unless, of course, people are wanting to pay for them themselves, which in my experience is very much the exception.”
Also, he says, someone’s future risk of fracture would be assessed in the context of other risk factors, rather than on a bone density measurement alone. He points out that osteoporosis isn’t actually a disease but a “process” that affects us all to varying degrees. “When I was a young doctor and saw someone who had a hip fracture in their eighties, you’d say, ‘Don’t you think we should start them on something to prevent another hip fracture?’, and [older orthopaedic surgeons] would say, ‘The horse has bolted here, forget it.’ There was this impotence, if you like.
“So there was a very active campaign to turn osteoporosis into a disease. That was the way people thought you would get it taken seriously – to sell it to governments and funders and to the doctors and to the patient. “I think that was quite politically sensible at the time, but I think it was conceptually wrong. Because you have people thinking, ‘Have I got osteoporosis or haven’t I?’ It’s a little bit like saying, ‘Have I got poverty or not?’ We’ve all got it to some extent.”
WHAT ABOUT UNDER-DIAGNOSIS?
Yet as Moynihan maintains, we need to be alert to the pendulum swinging too far – that the growing enthusiasm for prevention strategies can easily tip into “disease-mongering” – and in the process, making the worried well more worried, turning people into patients prematurely and diverting health resources from the people who are actually sick.
“One of the questions that people always ask when we talk about over-diagnosis or over-treatment is ‘what about under-diagnosis and under-treatment?’ The fact is there are multiple well-resourced industries doing everything they can to address the problem of under-diagnosis … there are very few people interested in the problem of over-diagnosis, apart from networks of researchers and clinicians and some consumer representatives.”
He notes there isn’t a lot of money to be made in over-diagnosis, but recognising the problem can help us figure out what to do about it, which can only result in a healthier society. “As a culture, we have to ask ourselves, ‘Do we want to see the very act of being alive as a risk for disease and death? Or do we actually want to free ourselves from a lot of these multiple unnecessary labels that we seem to be given from womb to tomb?’”
Or as John Cameron puts it: “We’ve all got what is called pre-death. It’s the disease you get before you die and we’re all suffering from it. So we’ve got pre-senile dementia, we’ve got pre-diabetes, we’ve got pre-heart attack … we’ve all just got pre-death. Get used to it.”