Problems with clinical trials

Clinical trials are at the heart of our progress in medicine. If we have a new therapy, clinical trials tell us whether it is better than the current one. They measure outcomes, but also look out for side effects and unexpected consequences of taking the therapy. They are absolutely essential to our progress, and it is vital that they are carried out properly and transparently.In recent years there has been an increasing awareness that our current mechanism to ensure this happens has been failing miserably. This has led to the formation of the All Trials initiative, which is campaigning for reform of the system. A paper this week in F1000Research emphasises the extent of the problems with clinical trials at the moment.The authors took a look at trials in the clinicaltrials.gov database. This is a database run by the National Institutes of Health in the US, and the FDA require that all clinical trials report a summary of their results there within 12 months of completion. What the authors of this study did was pretty simple: they mined the data for trials that were finished and also for those that had published their results. By comparing the two, they could figure out who was failing to share their trial results, and who was publishing.The study looked as far back as 2006, when it became a legal requirement for trial results to be published, so had a list of nearly 26,000 trials to analyse. The results were pretty stark. Over 45% of trials had not reported their results. This is a shocking but not unexpected finding. Previous studies had suggested such a high level of non-reporting, but this was the most thorough analysis to date.So why is it so important that results be published? Simply put, we need all the evidence about a treatment to understand its risks and benefits. The AllTrials campaign put it like this:

“If you tossed a coin 50 times, but only shared the outcome when it came up heads and you didn’t tell people how many times you had tossed it, you could make it look as if your coin always came up heads. This is very similar to the absurd situation that we permit in medicine, a situation that distorts the evidence and exposes patients to unnecessary risk that the wrong treatment may be prescribed.”

This is not an unfounded fear. In 1980, nine men died during a trial for a drug called Lorcainide, compared to only one in the placebo arm of the study. The manufacturer stopped the drug’s development (for commercial reasons rather than safety reasons), but crucially the researchers never managed to published the study. Over time other companies developed similar drugs, and they were prescribed throughout the 1980s. In 1993, the original researchers published their results, and the drug was removed from the market. Tragically, an estimated 20,000 to 75,000 people died every year from Lorcainide. It is essential that all the information is available when people’s health is on the line.A deeper look at the data published in this paper shows that some companies and institutions are a lot worse than others. This tool developed by the authors allows you to visualise this. The pharmaceutical company Sanofi, for example, has only published 150 of their 435 completed trials (35%). The Mayo Clinic, a prestigious Minnesota hospital and research centre, has not published 157 of their 312 trials (50%).Unfortunately, this issue has not been getting better with time. The most recent year that was analysed in this study was 2014, and in that year only 50% of trials were reported (see graph below), which is obviously unacceptable.This is a major issue in medicine at the moment, and one it is vital to be aware of. I would urge you all to sign this petition on the AllTrials website. The sooner this situation is rectified, the better.

Correlation vs Causation

The following headline caught my eye recently:

“Migraines could be caused by gut bacteria, study suggests”The Guardian – 18/10/16

To anybody who suffers from migraines, this is very interesting; at the moment, we really don’t understand what causes them. If a study has figured this out, then we may be able to help the estimated 15% of the population who are sufferers.This report is based on a paper published this week, titled:

“Migraines Are Correlated with Higher Levels of Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut Project Cohort”mSystems – 2016

The eagle eyed among you may have spotted the problem with this already. The Guardian has switched the word “correlated” for the word “caused”, so immediately you can see why the headline is wrong. Unfortunately the research did not show that gut bacteria cause migraines. What it did show was that people who suffer from migraines are more likely to have slightly different bacteria in their mouths than people who don’t. While this might lead you to think that there is a link, you cannot conclude this from the data. The difference between the two is easiest to explain in an example.The sales of ice-cream (A) correlates with the number of shark attacks (B). This could mean one of a number of things:

1. That A causes B.

Sharks are attacking more because people are buying more ice-cream.

2. That B causes A.

People are buying more ice-cream because of all the stark attacks.

3. That something else causes both A and B.

In good weather people go swimming more, and also buy more ice-cream.

4. That it is just coincidence that A and B are happening together.

Unlikely in this case, but actually extremely common, as I describe below.It is very, very easy to find correlations between random things. Take this fact, for example: the divorce rate in Maine is correlated with the consumption of margarine (see image below). This obviously does not mean that margarine causes divorces.Or the fact that the number of people who drown by falling in pools each year is correlated with the number of films that Nicholas Cage has been in that year. While it is tempting to suggest that Nicholas Cage films are so bad they are causing people to fall into pools, it seems a bit of an extreme reaction to his awful acting.These kinds of spurious correlations are everywhere if you look for them. There is a very good website (here) that mines data to find new ones, including the two examples I have used above. While these correlations are usually obviously nonsense, sometimes a correlation makes instinctive sense, and it is easy to believe that one thing is causing another, without actually having any evidence that it is true. This unfortunately can cause serious damage.As the rate of vaccination has increased over the last few decades, we have seen an explosion in the number of diagnoses of autism, which has led some people to claim that vaccines cause autism. It is an understandable assumption. The symptoms of autism appear at around the same stage as vaccination, so you can see why some parents jump to that conclusion. However, it has been clearly shown that there is no link between the two. In fact, the increase in the rate of autism is largely down to increased awareness and reporting, and not actually a result of more kids being autistic. Unfortunately however, the belief that these correlated events (autism onset and vaccination) are linked has led to a decrease in vaccination rates, and many preventable illnesses and deaths*.This problem of mixing up correlation and causation is common in the media, and an easy trap to fall into. Certainly correlation sometimes does mean causation, but without additional evidence we simply cannot say that it does. Correlation studies are common in science, and are an important research tool, particularly for informing future studies. Unfortunately, these are sometimes over-interpreted, and lead to things being linked without cause.The migraine study that I started this blog post with shows a correlation, but not causation. However, other studies have shown that chemicals that these bacteria produce can indeed cause headaches. While neither study is conclusive, it suggests that it may be worth following up these findings in further studies, which is exactly what the researchers recommend. Unfortunately, that wouldn’t make such a good headline. *It is worth pointing out that a certain percentage of people will get these illnesses, regardless of vaccinations. The numbers on the linked website above include these cases, so it is very difficult to know how many are directly due to decreased vaccination. It is clear though that the numbers have been increasing with decreasing vaccination rates, but if this blog post has taught you anything, it is that we cannot say that one has definitely caused the other. However, when combined with other available evidence, we can be very sure of that assertion. 

Hot drinks and cancer

You may have seen a frankly terrifying headline this week:

“Hot drinks probably cause cancer, warns World Health Organisation”Telegraph, 15th June 2016

Almost every news source carried this story, and the headlines were universally similar to the one above. This story comes from a report by the WHO, which looked at the association between coffee and mate (a South American herbal tea) and various forms of cancer. In short, they found that there was no association between coffee or mate and cancer, but that the temperature of the beverage may be linked to oesophageal cancer. This, of course, is nothing to worry about. The report classifies hot drinks as “probably carcinogenic to humans”, group 2A in their classification. Other items in this category are the act of frying food, working as a hairdresser or barber, red meat, and working night shifts. This categorisation tells us about the hazard of hot drinks, but not about the risk.The words "hazard" and "risk" are regularly used interchangable, so the distinction between them is one that is lost on most people. Hazard is whether something can happen or not. Risk is the likelihood that it will happen. There is a hazard of crashing when you are driving with your eyes open or with your eyes closed. However, the risk is quite different in each of these cases. This report tells us about the cancer hazard of hot drinks, but nothing about the cancer risk, so the fact that hot drinks are on this list isn’t very informative.So what do we know about the risk of hot drinks. Firstly, this applies to drinks consumed at 65°C or above. So if you put milk in your tea or coffee, then you’re ok. Even if you don’t, oesophageal cancer isn’t very common, so even a big increase in risk wouldn’t translate into many more cases (see below for an explanation of this). If you want to do something to decrease your already small chance of getting oesophageal cancer, then consider stopping smoking, stopping drinking, eating more fruit and veg or losing excess bodyweight, all of which are known risk factors.The system of classification used by the WHO is unfortunately ripe for misinterpretation. It is almost impossible to prove a negative, so proving something definitely doesn’t cause cancer is difficult. The WHO has now classified 1,051 different things for their likelyhood of causing cancer. Of those, they have only rated a single one as “probably doesn’t cause cancer”. (For those who are interested, that one thing is Caprolactam, a compound used in the production of nylon).Nearly half of the rest fall into the “not classifiable” category because we just don’t have enough evidence to say either way. This may be because the evidence is inconclusive, or because studies have never been done. In reality, if the WHO analysed whether swivel chairs caused cancer, they would fall into this category rather than the "probably don't cause cancer"one, because we have never needed to study it.So by the WHO system, we can't say that the following don't cause cancer: chlorinated drinking water, caffeine, mobile phones, fluorescent lighting, hair colouring products, magnets or tea. They are in the “not classifiable” category. However, aloe vera, pickled vegetables and dry cleaning are all classified as “possibly cause cancer”. As you can see, this classification causes more confusion in the general public than anything else.When you understand the difference between hazard and risk it becomes far easier to interpret the constant health scare stories in the media. “Mobile phones may cause cancer” is a terrifying headline, until it is put into this context. The increased understanding of risk is a vital tool in the rational toolbox. And because large parts of the media don’t seem to possess this, it is one that we can get a lot of use out of! Absolute risk v relative riskI mentioned above that even a large increase in risk of oesophageal cancer doesn’t mean many extra cases. To understand this you have to understand the difference between relative risk and absolute risk.Have a look at the diagram below. In both situations you have a 100% increase in relative risk. However, in one case this means your absolute risk goes from 1% to 2%. In the other  it goes from 35% to 70%.To to bring it back to hot drinks, imagine a crazy situation where they give us a 50% increase in risk for oesophageal cancer. (Just to be clear, there is not a 50% increased risk with hot drinks, I made that number up as an example of a large increase.)The rate of oesophageal cancer is around 15 cases per 100,000 people, so your risk of getting it is 0.015%. A 50% increase in risk means that the rate would rise from 15 to 22.5 cases per 100,000. In this case your risk has now gone from 0.015% to 0.0225%, an increase of 0.0075%.You can see how an enormous increase in your relative risk (50%) can mean only a tiny increase in your absolute risk (0.0075%). So when you hear someone say that x increases your risk of cancer, your first question should be “but what is the risk of me getting that cancer in the first place?”. Once you know that you will have a far better idea whether the rest of the claim needs to be listened to.

Kinesio Tape

Anyone who has watched any sport in the last few years will be aware of Kinesio Tape (KT). It’s the coloured tape that athletes wear to recover from/prevent injury. I really noticed it in the 2012 Olympics, when it seemed that every second athlete had some on, and it is still extremely prevalent.Manufacturers of the tape claim it can alleviate pain, reduce inflammation, relax muscles, enhance performance, and help with rehabilitation as well as supporting muscles during a sporting event. Furthermore, it can be used for hundreds of common injuries such as lower back pain, knee pain, shin splints, carpal tunnel syndrome, and tennis elbow, just to name a few. And all of this for as little as £8 per roll.Any product that claims to have such wide-ranging benefits deserves some scrutiny. So what evidence is there for KT effectiveness? Well, surprisingly little. In the last three decades there have been nearly 100 papers published regarding KT. In 2014, Australian scientists reviewed that literature and published their findings in the Journal of Physiotherapy. The paper was entitled: “Current evidence does not support the use of Kinesio Taping in clinical practice: a systematic review”, and the title says it all. They reported that “Kinesio Taping was no better than sham taping/placebo”. Furthermore, in studies that did show an effect of KT, the scientists found that either the effect was tiny and probably not clinically significant, or that the trials were of low quality.A second review in 2013 concluded that “there currently exists insufficient evidence to support the use of KT over other modalities in clinical practice”. It is pretty clear that KT does nothing that ordinary tape doesn’t do.So it’s no better than standard taping; but what does standard taping do? Again, the literature is pretty mixed on this. There is some evidence that taping an injured muscle may help it perform better, just like a brace. It is also thought to offer slight pain relief by structurally supporting a joint, however, a brace is more effective. There is also some evidence that it can improve proprioception (the awareness of where a limb is in space without looking), but this is disputed. Ultimately, taping can help with an injured joint or muscle, albeit in a minor way.So given that using gaffer tape works just as well as KT, why is it that sportspeople spend the extra money on expensive KT? Marketing is the obvious answer. In both the 2008 and 2012 Olympics, Kinesio Holding Co. donated huge amounts of tape to the US Olympic Committee. American beach volleyball player Kerri Walsh embraced the product and the company saw a 300% rise in sales in the immediate aftermath.Selling to athletes makes perfect sense really. They are well known to be a superstitious group of people, and those superstitions can help them perform better. Michael Jordan played every single game of his career in the same pair of shorts from the University of North Carolina. Serena Williams never changes her socks during a tournament. In the arena of elite sport, small margins can be the difference between winning and losing, so the placebo effect of a particular ritual can be decisive.Ultimately, Kinesio Taping is just the latest in a long list of products that sports people have embraced because they thought it gave them the edge (who remembers those white strips that people used to put on their noses to make it easier to breathe?). Ironically, although these products themselves do nothing, the belief that they do may have a minor effect. Unlike other pseudoscience I have written about, this isn’t a particularly harmful one. So if someone wants to spend their hard-earned cash on magic tape, who am I to object?!

Alternative medicine as a placebo

I recently wrote a post about the decision by NICE to no longer recommend acupuncture for lower back pain. This decision was made because, like most alternative medicine, acupuncture hasn’t been shown to work any better than a placebo. However, plenty of people use and get benefit from such treatments. This raises an interesting question: is there a place for complementary and alternative medicine (as a placebo) in the clinic?The ethics of prescribing placebos is a complicated topic. People are perfectly entitled to use alternative medicine, and if they get a benefit, that’s obviously good. However, whether a doctor should prescribe alternative medicine is a different matter.As I have previously written, most complementary and alternative medicine works purely on the placebo effect. People argue that alternative medicine should be allowed to be prescribed, because if the placebo effect helps someone, then that justifies its use. Indeed, here in Glasgow we have an NHS funded “homeopathic hospital”, and if it helps people, why should we stop that?Unfortunately it’s not that simple. If a doctor prescribes such a therapy, it has the effect of offering a medical credibility to the therapy that doesn’t work. This may not sound like a big problem, but it is. There are many examples of people eschewing mainstream medicine for “natural” alternatives and herbal remedies.A court in Canada, for example, recently convicted the parents of a child who died from meningitis after they consulted a naturopath rather than a medical professional. The naturopath recommended the parents give ecinachia to their dying child. This isn’t an isolated case; it’s worth visiting the What’s the Harm website to see the toll that belief in pseudoscience can have.The reality is that if a doctor prescribes acupuncture for pain, then a patient is more likely to believe the plethora of false claims that an acupuncturist may make (including it being effective against diabetes, heart attacks, cancer and even ebola). This in turn increases the risk of patients postponing or declining evidence-based conventional treatment when it is needed. It was recently shown that women who were using certain alternative therapies were less likely to start chemo for their breast cancer. Regardless of whether someone benefits from the placebo effect given by an alternative therapy, it is simply not ethical to legitimise it as a practice. Furthermore, it is perfectly possible to give a placebo that does not come with the added nonsense, which brings me on to my next point.In 2008, the American Federal Trade Commission made a ruling on the use of the Q-Ray Ionised Bracelet in medicine. The makers argued that they could claim it was a cure for chronic pain because, like acupuncture and other alternative medicine, it exhibited the placebo effect. In his ruling on the case, the judge said the following:

“Like a sugar pill, it alleviates symptoms even though there is no apparent medical reason. Since the placebo effect can be obtained from sugar pills, charging $200 for a device that is represented as a miracle cure but works no better than a dummy pill is a form of fraud.”

When we can get the same or similar effects from a far cheaper placebo, then a doctor prescribing alternative medicine is ripping off their patient or the NHS. With already stretched resources, it is scandalous that the NHS pays £1.33 million per year to the Glasgow Homeopathic Hospital. People spend a huge amount of money on alternative medicine (it’s a $34 billion industry in the US), a product that doesn’t work, and is also completely unregulated.The unregulated nature of the industry is something that people are generally unaware of. Numerous studies have shown that alternative remedies regularly contain contaminants like toxic metals, pharmaceuticals, insects, rodents, parasites, fungi, pesticides and other fillers. These contaminants have led to serious illness is many cases, and several deaths. Prof. Edzard Ernst (former Chair in Complementary Medicine at the University of Exeter) has written extensively about this topic and is a good place to look for more information.The placebo effect has a significant role to play in health care. It can undoubtedly improve subjective symptoms in a number of contexts. However, while any effect alternative medicine has can be explained by placebo, the industry claims that it does much more than that. Couple this with the unregulated nature of the products and the expense involved, and it is clear that alternative medicine should never be given legitimacy by the mainstream medical community. I’ll leave you with this quote from Tim Minchin: 

"By definition", I begin"Alternative Medicine", I continue"Has either not been proved to work,Or been proved not to work.Do you know what they call "alternative medicine"That's been proved to work?Medicine."

https://www.youtube.com/watch?v=HhGuXCuDb1U

Royal College of Physicians recommends e-cigarettes for smokers

A few months ago I wrote here about the rise of e-cigarettes. In that post I pointed out that e-cigarettes are far less harmful than tobacco, and should be marketed as a safer alternative to smoking. There has been an interesting update on this topic today, with the Royal College of Physicians (RCP) recommending that all smokers be offered and encouraged to use e-cigarettes.You can read my previous post for some of background, but put simply, e-cigarettes vaporise nicotine to allow it to be inhaled (hence it being known as “vaping”). This differs from smoking, where tobacco is burned and the smoke inhaled. This accounts for the primary difference between vaping and smoking; tobacco burning creates thousands of chemicals, 10% of which are known to cause cancer. People inhale far fewer chemicals when vaping, making it 95% safer than smoking.The RCP released a report today (April 28^th) stating that

"e-cigarettes are likely to be beneficial to UK public health. Smokers can therefore be reassured and encouraged to use them, and the public can be reassured that e-cigarettes are much safer than smoking"

They go on to state that current evidence shows:

• E-cigarettes are not a gateway to smoking.
• E-cigarettes do not result in the normalisation of smoking.
• E-cigarette use is likely to lead to quit attempts that would not otherwise have happened.
• The dangers of long-term e-cigarette are unlikely to exceed 5% of those associated with smoked tobacco products, and may well be substantially lower than this figure.

An excellent Cancer Research UK blog post on this topic points out that this reduced harm of vaping is something we should focus on. They emphasise that a significant number of people may be unable, or simply not want, to give up smoking. For these people, the aim should be to reduce the danger of their habit by encouraging them to use e-cigarettes rather than traditional cigarettes. This harm reduction strategy has worked well in other cases, such as needle exchanges for intravenous drug users.This is what the NHS already recommends, in the form of nicotine replacement therapy. It has been shown, however, that the delivery of nicotine to the brain via vaping is far more similar to smoking than in nicotine replacement therapy. As a result smokers seem to prefer vaping, and e-cigarettes have now replaced nicotine patches and gum as the most popular aid in quitting smoking in the UK.It has been shown that an overwhelming majority of e-cigarette users are ex-smokers, or current smokers who are trying to cut down or quit. Considering the human toll of smoking (270 deaths in the UK every day), it is commendable that the RCP have recommended e-cigarettes to smokers. While there are still problems with vaping (particularly in marketing to children), the advantages for current smokers are undeniable. The use of alternative sources of nicotine is safer, and should be part of any strategy to reduce the harm of tobacco.

The placebo effect

The recent decision by NICE to no longer recommend acupuncture for lower back pain got me thinking about the placebo effect. It is a bizarre phenomenon: any treatment (regardless of whether it is a real treatment or not) will improve symptoms in some people simply because the recipient believes that it will work. So if we give someone a placebo (a sugar pill for example) and tell them that it can work for their illness, a proportion of patients will feel better. There are so many interesting things about the placebo effect it’s difficult to know where to start.The more the placebo, the bigger the effectTake this observation: if we give someone sugar pills as a placebo, then they might see improvement in their symptoms. However, if we give them four sugar pills instead of two, then we will see a bigger improvement. And if a placebo injection is used, then this is more effective again.It matters what a placebo looks likeSugar pills with a brand name stamped on them will have a stronger placebo effect than those that don’t. Researchers have also found that sugar pills with a $2.50 price tag ease pain much more effectively than identical pills with a10 cents tag. We actually see the same effect with wine; people rate a wine highly if they think it is more expensive.You don’t necessarily have to deceive peopleBizarrely, there is still a placebo effect even when the patients know they are getting a placebo. When researchers told people who were on a trial for an irritable bowel syndrome that they were receiving “placebo pills made of an inert substance”, they found that patients still experienced a reduction in symptom severity, even though they knew they were on a placebo. In another study, researchers gave patients a fake pain-relieving gel for 4 days, and then told them the truth, that it was it was actually just dyed vaseline. However, the pain relieving effect still persisted after this, suggesting that conditioning is part of this effect.The placebo effect is getting stronger with timeResearchers analysing 20 years of clinical trials for pain have noticed a weird pattern: the placebo effect has been increasing over that time (but only in the US). Several explanations for this have been suggested, including that patients are getting more attention and encouragement now compared to the past, so their overall experience in the trial is better. It has also been pointed out that over this time pharmaceutical companies have turned to private companies to run their trials. As these companies are paid to recruit more people, they may inadvertently include less ill patients on the trial in order to boost numbers. This has been shown to result in an apparent treatment effect in patients, contributing to the placebo effect.There is a placebo effect on animalsThis is a really confusing one: animals experience the placebo effect! If this effect is driven by the expectation that the treatment will work, how do we explain that? More about that below.Placebos can cause side effectsWhen patients are aware of the side effects of a treatment, they can also experience these while on placebo. For example, if a patient has previously taken opioid pain relief (one related to opium, such as morphine, codeine or vicodin), which can result in respiratory depression, they are then more likely to experience the same symptoms when on a placebo. Furthermore, if someone has been on hormone replacement therapy (HRT) placebo and this is then discontinued, they can experience the same withdrawal symptoms as someone who has actually been on HRT.And placebos aren’t just a medical thingThe placebo effect exists in other areas of life too. After drinking placebo vodka, people’s IQ drops and they have impaired judgement. This is demonstrated with predictably funny results in a video of a non-alcoholic keg party that you can find here.The above examples all point to the fact that while the placebo itself is an inert substance, it can still result in real physiological effects through suggestion, expectation and other mental processes.We really don’t have a good grasp on how the placebo effect works. We know that it usually affects subjective symptoms like pain, depression, hot flushes, and insomnia, but that it very rarely improves the underlying disease mechanisms. Survival from serious forms of cancer has little observable placebo effect for example. However, we do know that it is made up of a mix of different biological and psychological factors.First and most obvious of these is that mood and belief can have a significant effect on subjective symptoms, both through our perception of those symptoms, but also through real biological mechanisms. When studying the placebo effect in pain research, scientists found that a drug called naloxone, which inhibits opioids, could also inhibit the placebo effect, suggesting that placebo and opioid pain relief share a common mechanism. Other scientists then used brain imaging to suggest that placebo and opioid pain relief both seem to work via the same pathways in the brain, showing that for pain relief at least, part of the placebo effect is caused by a real biological mechanism.Such biological mechanisms are also at play in systems where mood really matters. The placebo effect can lower the release of stress hormones (through altering someone’s mood) and as such can have an effect on the heart and the immune system. The influence of a placebo in this context is mild, but almost certainly real.These biological explanations are in the minority however; it is thought that most of the placebo effect is as a result of cognitive biases that we are all prone to. Before I get into that however, I will point out that, placebo or not, if someone feels better after taking something, then it may have legitimate use in medicine. I won’t address this issue here, but will in my next post on this blog. The use of alternative medicine falls into this category, and is an interesting topic.Back to the placebo effect; the most common cognitive bias that falls into this category is called regression to the mean. The many so-called “cures” for the common cold (echinacea, hot lemon, etc.) are a great example of this. We can show that these none of these remedies have any effect above the placebo. However, when people get better they credit whatever treatment they have taken for this natural improvement in their symptoms. Often, by the time someone starts their herbal remedy (or whatever they decide to go with) their body has already dealt with the illness and they are on the mend. It is very natural for us to see cause and effect where there is none, but most improvements like this are as a result of the placebo effect, specifically regression to the mean.The animal placebo effect mentioned above can be explained by another bias we are prone to called the caregivers effect. This occurs because animals cannot directly report their subjective symptoms, so people have to observe the animals and decide whether they are responding to the therapy. Often, the humans will perceive improvement even when objective measures show none.In human trials, other biases occur. People taking a treatment want to get better and want the time and money they have invested to be worthwhile, so when they are asked to rate their symptoms, they tend to over-estimate their improvement. This is known as reporting bias, and also affects scientists, who want their treatments to work and will tend to over-estimate the positive effect in their trial.It is also known that simply being in a clinical trial can contribute to the placebo effect. Participants tend to take better care of themselves than normal, and also get more medical attention than people not in trials. This causes improvements in people on the trial, not because of any biologically “real” placebo effect, but simply because they are part of the trial. This is known as the clinical trial effect.The placebo effect is an incredibly fascinating thing. It shines a light on how much we do not understand about our bodies, but also on how much tricks of the mind can affect our perception of ourselves. I began this article by talking about acupuncture, but the role of the placebo effect in alternative medicine is not one I will address in this post. However, I will tackle this, and the question of whether it is ethical to prescribe a placebo, in my next piece on this topic.

Why screening is hard

It’s a simple fact that the most effective thing we can do to cure more cancers is to catch them earlier. If we find bladder cancer at an early stage, the five year survival is 88%; if we catch it at a late stage, when it has started spreading around the body, it drops below 15%. This is why we screen for certain diseases, including breast, bowel and cervical cancer. These large-scale screening programs are the best hope we have for majorly reducing the toll cancer takes on our lives.Screening, however, is hard. The main problem we face is accuracy. An ideal test would flag up 100% of sick people and 0% of healthy people. However, these tests are never perfect. There is always a percentage of sick people who are not flagged up (false negatives) and a percentage of healthy people who are incorrectly labelled as sick (false positives). And these problems can get pretty bad pretty quickly.The following diagram illustrates this issue. It shows the results of a test that is quite accurate (one that has 90% accuracy) applied to a common disease that is present in 1% of the population.As you can see above, what sounds like a good screening test results in 10 times more false positives than true positives, while it also tests one person as negative while they are actually positive.In a large population, even a small percentage of error translates into a large number of misidentified patients. This can result in a crippling financial burden on the health system, as well as unnecessary worry, stress and pointless treatment for perfectly healthy people.As a result, only extremely accurate tests can be used in the clinic, which is the reason we screen for so few diseases. So how do we get around this? Well, obviously we have to develop more accurate tests, and a lot of effort is currently being invested in this field.Additionally, we can also improve things by being more selective about the people we screen. If a disease is present in 1% of the general population, but present in 5% of people over 65, then we can screen just the over 65s.So using the above the example of a test with 90% accuracy, if the prevalence is 5% instead of 1%, then rather than 10-times more false positives than true positives, there is just over 2-times. If the test were 98% accurate, then we would have far more true positives than false positives. This increased accuracy in a specific population is what we are working towards.However, while significant research is being carried out in the development of new tests, it is disappointing to note that this is still a small percentage of cancer research funding. According to the National Cancer Research Institute, in 2011 (the most recent year I could find numbers for), research into early detection, diagnosis and prognosis received just 12.6% of cancer research funding.While it is understandable that research into a “cure” is more attractive than research into early diagnosis, the potential benefits of early diagnosis far outstrip that of drug development. Encouragingly, this level of funding is increasing steadily, and rose from 8.1% in 2002 to 12.6% in 2011. If this research can result in more viable screening programs, this will provide a significant clinical benefit to cancer patients.For more information about screening, I’d recommend having a look at the sense about science website, which does a great job of describing not just this problem, but also many others that arise in screening populations for diseases.

Acupuncture no longer recommended for back pain

NICE (the organisation that provides guidance to doctors in the UK) recently updated their recommendations regarding lower back pain. In the updated guidance, they say that exercise, in all its forms (for example, stretching, strengthening, aerobic or yoga), is the most important step in managing back pain. Previously, NICE also recommended acupuncture or massage, but this has now been altered. Massage can still be used alongside exercise, but the guidelines no longer recommend acupuncture, as "evidence shows it is not better than sham treatment".This is not entirely surprising as, despite widespread acceptance of acupuncture, the evidence that it works for any illness or disability is very scant (as I have described in a previous post). Most studies are poorly carried out, and many show no difference between it and sham acupuncture.Unfortunately, the authors of these studies often conclude that both acupuncture and sham acupuncture work, rather than the actual conclusion (that acupuncture doesn't work). If a medicine works no better than a sham medicine (a sugar pill for example), we cannot conclude that both the medicine and the sugar pill work.For those suffering from back pain, the new recommendations also encourages people to continue with normal activities as far as possible, and recommends that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or aspirin should be tried. Unfortunately, at present there is no evidence to back up other interventions.A recent study found that back pain caused more disability than any other condition, and is also responsible for 37% of all chronic pain in men and 44% in women. While it is understandable that people seek relief from their symptoms, it is obvious that the NHS can't fund a treatment that does not work.

Profiteering

We all know that pharmaceutical companies provide an essential service. They produce all the drugs needed to keep us healthy, and fund a large portion of the research into new therapies.However, it is also the industry with the highest profit margins, higher than oil and gas, higher even than the banking sector. And an industry doesn’t win that crown without their fair share of underhandedness.A pretty blatant example of this was reported in the New York Times recently. They described a study, published in the BMJ (the British Medical Journal), which highlighted a simple but effective way the drug companies force consumers in the US to buy more than they needed. All they do is package it in a bigger vial than required.The authors highlight Keytruda, a new drug for lung and skin cancer, as an example of this. An average patient would need around 136 milligrams of the drug, but the company only make it available in the US in 100 milligram vials.As a result, doctors give the patient their dose and then usually discard the rest of the vial, ensuring a high level of waste. However, the patient/insurer gets charged for the full amount, inflating the profit of the drug company.The study examined the top 20 cancer drugs that are dosed by body size and packaged in single dose vials. This accounted for 93% of all such drug sales. The study showed that an average of around 10% of the drug was discarded due to packaging. The therapy ipilumumab, for example, would have an average of 7% left over in each vial. Considering that a dose costs $29000, this means that the company are making an additional $2000 for every single vial they sell.You can find a nice little tool here which shows the estimated wastage per drug that was analysed in the study.In total the authors estimate that in 2016 alone pharmaceutical companies will make an additional $1.8 billion from this practise. And this is just from cancer drugs. The asthma drug omalizumab is dosed in multiples of 75 milligrams, but the company only sells 150 milligram vials in the US, even though it has an approved 75 milligram vial size. The authors estimate that the drug infliximab (used for intestinal disorders and arthritis) generates around $500m each year in additional revenues from leftover drug. Overall, the profit made from this forced wastage is significantly higher than the $1.8 billion that the companies get from cancer drugs, probably around $3 billion.To add insult to injury, this is just the increased revenue that the pharmaceutical industry makes from leftover drug. Patients in the US are also charged a mark-up by doctors and hospitals, which is usually dependent on the amount of drug in the vial, not the amount of drug used. This is thought to add an additional $1 billion to what consumers are being charged each year.It is worth pointing out that this is largely a problem with the American health care system. In most other countries (where the government has more control over what is spent on health care) the drugs come in various size vials, so the waste is minimised. Keytruda, for example, is sold in Europe in 50 milligram vials (as opposed to 100 milligram vials in the US), so while the waste is still considerable, it is far less than that in the US. Furthermore, it is standard procedure to prepare a number of patient’s doses at same time and share the vial, so that the amount of waste is minimised and money saved. This is not a common practise in the US.I have touched upon the pricing of pharmaceuticals in a previous blog post, and it is quite a controversial issue. The industry likes to present itself as largely ethical, generating high levels of profit primarily to fund further research. However in this case companies are deliberately producing waste in order to maximise profit. Unfortunately, blatant profiteering like this (at the expense of the consumer) undermines this argument.

Recent advances in cancer therapy

First off, sorry for the lack of writing in the last few weeks; I’ve been in the middle of a job hunt, so my time has been limited by that. In the time I have taken off however, there have been some major news stories about cancer.The week of the 15^th February brought some pretty sensational headlines. These were about a trial of a new immunotherapy, which both The Times and the Independent proclaimed “a cure”, and The Guardian labelled as “unprecedented”.Immunotherapy is an extremely promising branch of cancer therapy that has recently been getting a lot of attention. I have previously written about it here, so I won’t go into detail about how exactly it works. Simply put, it involves taking some of a cancer patient’s immune cells, teaching them to recognise the tumour, and then putting them back into the patient. These immune cells can now identify the cancer, attack it, and hopefully clear it from the system.These results have not been published yet (they were presented at a conference), so we can’t say for sure how reliable they are. We do know however, that the trial had just 36 patients on it, and that it was looking at a cancer we can already treat with a high degree of success (acute lymphoblastic leukaemia (ALL)), so the headlines were far more sensational than the work deserves. That being said, it does appear to be a very encouraging study. However, as I have previously written, claiming something is a “cure” for cancer is likely to be wrong.This treatment appears to be very effective for ALL, and it may eventually become part of the standard therapy for this disease. However, ALL is just one of a large number of different types of cancer. Couple this with the ability of the disease to develop resistance to therapy and it becomes unlikely that this (or any other therapy) will ever be a “cure” for cancer. So while this is certainly an exciting advance, claiming it is a cure is unfortunately incorrect. It may have the potential to cure some patients, but without long term testing, we just don't know if this is the case.This problem of resistance brings me to the second big cancer story that’s been in the news recently. Coincidentally, it is also to do with immunotherapy. In this study, scientists found that a patient’s cancer carry markers that the immune system could be primed to attack, as I described above.However, it has always been assumed that as a tumour develops, it would change and evolve, resulting in some cells that no longer have these markers, and would therefore be resistant to the immune cells taught to target those markers. What is interesting about this study is that the scientists showed that this may not always be the case, and that all of a patient's tumour cells may still carry the markers, meaning they would all be attacked by the immune system. The video below (from CRUK) describes this very nicely.https://www.youtube.com/watch?v=ZPwrvPerxIkThe potential that a patient won't develop resistance to a therapy is one that scientists and doctors can only hope for. If this study holds, and is extended to other cancers, this dream may become a reality for some people. Again, this is a study on very few patients, but it gives us a tantalising glance at a potential weakness in cancer that could be exploited.It is an exciting time to be a cancer researcher!

Trust in science

As with every other week, the last 10 days has brought a slew of tabloid stories, linking various things with causing or curing cancer:GOOD: antacids, Chinese herbal remedy, berries and tea, anthrax, frying foodBAD: being tall, tonsils, artificial football pitches, The RAF, oral sexAs always, these stories are largely nonsense, suitable only for the bin. Unfortunately, they are reported credulously and are widely read, and this saturation of health-related articles has several negative consequences.The constant bombardment of people with often-contradictory health information can drown out real health advice, making people think that eating some nuts can offset the effects of a terrible lifestyle for example. There is an enormous industry based on the peddling of cancer-preventing foods and supplements, often with a thin veneer of scientific respectability, and thanks to tabloid reporting, a much wider reach than should be allowed. It’s infuriating.However, the most insidious problem with poor media portrayal of science is the gradual erosion of trust in science. This may not seem like a significant issue, but it may be the most important. The rejection of vaccines, denial of climate change and resistance to genetic modification of foods, for example, are all rooted in science denial.This is an issue with many causes. Both political and religious beliefs play a major role in our view of the evidence, as does self-interest, meaning that arguments are often politicised or financially motivated. When Andrew Wakefield, for example, “found” a link between vaccines and autism, he personally profited from people not using the MMR.The driving force behind denialist movements are often organisations that stand to gain from the confusion (climate change denial has largely been funded by groups that will suffer most from restrictions on fossil fuels). There has been a deliberate drive to manufacture controversy in many areas, most famously by the tobacco industry, whose tactic was not to win the debate, but to “foster and perpetuate the illusion of controversy in order to muddy the waters around scientific findings that threaten the industry”. A leaked memo to George W Bush on climate change tactics from 2002 suggested that although the scientific debate was closing, it was important “to continue to make the lack of scientific certainty a primary issue in the debate”. Media organisations are often complicit in this, and there are many examples of the deliberate undermining of the scientific process, most notably by Fox News in the US.That being said however, the large majority of people who subscribe to denialist views are people who have no such motivation. These people appear to have a basic mistrust of science, and are swayed by the anti-science rhetoric. It is easy to understand why parents hesitated to vaccinate after the initial reports of a link to autism, but despite this link being definitively shown to be false, vaccination rates in large parts of the world are still suffering. Be it the left-wing embracing of alternative medicine, the right-wing support of climate change denial or religious creationism, the anti-science movement is a pervasive one, largely based on the mistrust of science.There are several roots of this mistrust. An obvious one is that science can undermine deeply held beliefs. When this happens, people are likely to reject the evidence, rather than give up their belief. In fact, when challenged on such a belief, people are more likely to strengthen their belief rather than the other way around (known as the “backfire effect”). This needn’t be a religious belief, and is something that has been observed in many areas of life, such as the belief in superstition or alternative medicine. If science continuously challenges these beliefs, then people stop believing in the science.It is also the case that a misunderstanding of what science actually is also contributes to this issue. Many people see science as an “institution”, something that is telling us what to do. The reality is that it is a process. This misunderstanding of science makes it much easier for people to rationalise the rejection of valid conclusions, regardless of the strength of the evidence. The power of anecdotal evidence is a classic example of this: “my father smoked 20 a day, and he lived ‘til he was 90”. This view of science as an “institution” also feeds into an anti-establishment mentality that can also result in science denial. This is the same mentality that is behind the belief in grand conspiracies.And this brings me back to the tabloids. If you are told every day that random things are making you sick, or are essential to health, it is likely that you will become desensitised to them. It is easy for people to reject science-based advice, because tabloid reporting makes science appear far more confused than it actually is. The reporting of preliminary findings, or of badly carried out science, leads to a confused picture of our current understanding. Scientists are constantly studying and learning, working towards the truth. Bad science and incorrect results are inevitable in science, but it is a self-correcting process that gradually works to show what is real and what is not.Our entire civilisation is based on scientific innovation and progress. While that progress cannot be halted, it can be slowed by the mistrust of the public in the scientific process. That can only be a bad thing.

Smoking vs Vaping

Vaping has become remarkably popular in the UK over the last few years. Estimates now suggest that over 2.5 million people in the UK use e-cigarettes and that number is rising. However, as a recent conversation with my wonderful sister-in-law showed me, people are divided over whether this is a good thing or not.Smoking is one of the most damaging habits we can choose to take up, being the single biggest cause of preventable death in the UK (as I described in a previous blog). We have known for years that people “smoke for the nicotine, but die from the smoke”; standard cigarettes burn tobacco, generating over 7,000 different chemicals, at least 72 of which are known to cause cancer.In contrast, e-cigarettes vaporise nicotine to allow it to be inhaled. This difference is perhaps the biggest argument for vaping that can be made, as most current evidence suggests that it is far safer. Public Health England (a UK governmental body) estimates that e-cigarettes are “around 95% less harmful that tobacco”, leading 53 experts to recently write a letter to the WHO, urging them not to classify e-cigarettes the same as regular cigarettes. Furthermore, the Royal College of Physicians has also called for e-cigarettes to be marketed as a less harmful alternative to smoking.However, it is important that e-cigarettes are seen as the lesser of two evils, rather than as something “good” or “safe”, a fact that seems to be ignored by advertisers, who benefit from a lack of marketing regulation that applies to other addictive substances like cigarettes, alcohol or gambling.There is pretty good evidence now that several cancer causing agents can be found in e-cigarettes. Some of the flavourings added to e-cigarettes have been found to contain high levels of chemicals known to cause lung cancer. Furthermore, the well-known carcinogen formaldehyde has been identified at levels 5 times higher than in normal cigarettes. This study has not been replicated however, but it is worth keeping an eye on.Additionally, nicotine itself is a poisonous substance, particularly in pregnancy, as it can both cross the placenta and is present in breast milk. While the dose of nicotine supplied by an e-cigarette is lower than that supplied by a regular cigarette, it is overwhelmingly clear that people should neither smoke or vape during pregnancy.Finally, it is important to discuss the potential of vaping as a gateway drug to smoking. Do people who would otherwise not smoke take up vaping? There isn’t a huge amount of data to answer that question right now, and the data we have is mixed.Some studies suggest that this may not be the case, and the increased e-cigarette use is resulting in a decreased in the number of new smokers. However, other studies have shown the opposite, that many teens that use e-cigarettes do so for the novelty and flavour. The two biggest studies show that only a subset of those considered “gateway smokers” will move on to be regular smokers however, meaning that it is likely that further follow-up studies “will be unable to demonstrate a major gateway to heavy tobacco use”.E-cigarettes have only been on the market for a few years, so it is impossible to tell what the long-term effects of their use will be. While there still isn’t sufficient evidence to be sure, indicators suggest that vaping is a lot less dangerous than smoking, so it probably makes sense to market e-cigarettes as a safer alternative for nicotine addicts.However, making e-cigarettes attractive to teenagers and children should obviously be banned. It is extremely worrying that many flavours currently available are targeted at kids (including “cotton candy” and various fruit flavours). After all, nicotine is an extremely addictive substance, so the normalisation of vaping in this group should be prevented.This current lack of regulation needs to be corrected, but it must be acknowledged in any regulation that e-cigarettes are less harmful than regular cigarettes, and that excessive regulation may drive people to smoking in order to get their nicotine fix. Given the horrendous toll of tobacco smoke, this is something we cannot allow.

Gluten-free diets

The last few years have brought an increased awareness of the presence of gluten in our diets. In line with this, the Daily Mail recently ran an article headlined “Could going gluten-free boost your brain power? Landmark study reveals diet 'reduces fatigue and increases energy levels'”.The article in question was published on the Mail Online. In it they report on a study that links a gluten-free diet to decreased fatigue, flatulence and bloating. There is so much wrong with the piece it’s difficult to know where to begin, so I’ll start with the most concerning issue: that the study was funded by Genius Gluten Free Foods.That’s right, this “Landmark” study was funded by the very people who will benefit most from its result. This fact alone throws up big red flags, but reading further brings up some other major issues.The study has not been published, neither online or in a peer-reviewed journal. I contacted the University of Aberdeen, The Rowett Institute and authors of the study, to try to get my hands on the data (or the press release the journalist was working from), but to no avail. From the article in the Daily Mail, I can say that the study itself had fewer than 100 people in it, far too small a sample size to say anything concrete unless the study used extremely stringent criteria (which it did not).Furthermore, the article itself points out that the participants ate a healthier diet while on the study, making it entirely possible (and likely) that the effects seen were not as a result of the gluten-free diet, but as a result of eating better in general.I could go on all day, but I’ll leave it at that. The article is clearly rubbish, but it does highlight the recent popularity of gluten-free diets however, and this is a topic about which there is a lot of controversy.Removing gluten from the diet has become big business. According to the BBC, 29% of American adults (70 million people) say they are trying to cut back on gluten. This results in a gluten-free market in the US of almost $9 billion. Here in the UK, sales of gluten-free foods were around £184 million in 2014, which shows just how common it has become.It is safe to say that there are certainly people who do benefit hugely from a gluten-free diet. These are people with coeliac disease, an autoimmune disorder that results a decrease in the ability of the intestine to absorb the nutrients it needs. It is thought that around 1% of the population have some level of coeliac disease, so it is a relatively common disorder. Additionally, most of that 1% are undiagnosed, so it is certain that a gluten-free diet can improve the symptoms of some people.Another group that may benefit from the diet are those with non-coeliac gluten sensitivity, but this is controversial, as it has not yet been shown that gluten sensitivity actually exists. The most definitive study into this (in 2013) showed that gluten was not causing the symptoms of the patients in their study. They laid the blame at the door of a group of carbohydrates known as FODMAPs (which are partially eliminated in a gluten-free diet). Other research has blamed ATIs, plant proteins that are common in grains. Regardless, diet clearly influences the symptoms in these people.With the caveat in mind that going gluten-free will help some people, it must be pointed out that the large majority of people trying to reduce the gluten in their diets have no need to. Studies have shown that at least two-thirds of people who claim they have non-coeliac gluten sensitivity cannot tell if they have been exposed to gluten or not. The design of that study also makes us confident that this is an underestimation. The same study showed that symptoms often got worse if the subjects thought they were eating gluten, suggesting that the nocebo effect plays a large role in their symptoms (I’ve previously written about the nocebo effect here. Put simply, it is an ill effect caused by the suggestion or belief that something is harmful).“Gluten-free” is a fad diet, albeit an extremely popular one. Gluten is widely perceived to be unhealthy, a contention for which there is little evidence. Celebrities (Gwyneth Paltrow, Miley Cyrus) and sport stars (Novak Djokovic) have further propagated this myth, leading to the boom in sales we have seen recently.The problem is that there are risks attached. It is known that some foods that are free from gluten are actually less healthy than the original variety because they may contain more fat or sugar and thus more calories. In order to attain the same texture and consistancy, starches and binding agents are often added. It has also been shown that avoiding wheat products can lead to deficiencies in nutrients such as folate.The majority of people who are gluten-free do it because they are under the impression that it is better for you. In reality, they are spending more money on products for no real benefit, and feeding an industry that encourages people to unnecessarily buy more expensive foods. Eating more fruit and vegetables is a much wiser investment.As I’ve already pointed out, there are people who benefit from a gluten-free diet. However, that is not the case for the majority. I’ll leave the final word to Dr. Ruth Kava, who is a Senior Nutrition Fellow at the American Council on Science and Health. She commented that “The bottom line is that if you don’t really need to go gluten-free, don’t bother. And to determine if you do, consult a gastroenterologist, not a celebrity diet guru.” Well said.

A new technique to tackle malaria?

This week brought news of a fascinating new approach to preventing malaria. Malaria is an illness caused by a parasite that is spread by mosquitos and causes 219 million illnesses per year, and 500,000 deaths.This statistic however, doesn’t convey the extent of a problem malaria poses. It is a disease that kills vulnerable people in countries least equipped to tackle it: 90% of those deaths occur in sub-Saharan Africa, and shockingly almost 80% occur in children under 5 years old (400,000 deaths).Furthermore, economically, it is thought to impact the GDP of some countries by up to 5 – 6% per year (Nigeria and the DRC for example). To put that into context, the same problem in the UK would cost the country around £120 billion; the entire annual budget of the NHS is £95.6 billion.It is easy to see how this disease is financially ruinous for sub-Saharan Africa, and how big an affect fewer cases of malaria could have.This is why it is big news that a strain of mosquito that is resistant to the parasite (and thus cannot spread the disease) has been created in the lab.The scientists introduced a gene into the DNA of the mosquitos, one that gives the insect an antibody against the malaria parasite. This antibody causes the insect’s immune system to kill the parasite. In tests, the researchers found no transmission of the disease by these mosquitos.This is an impressive feat in itself; however on its own it isn’t much use. This is because every individual has 2 copies of every gene, and only one copy is transmitted to the offspring. So normally the modified mosquito would pass its copy of the resistance gene to half its offspring (see figure, below). They in turn will pass it to half their offspring, and so on. Very soon the resistance gene would be naturally drowned out of the population.This is where a second bit of technology comes into play. The scientists took advantage of something called a Gene Drive, a system aimed at forcing the expansion of a gene in a population using Crispr/Cas9 technology, Crispr/Cas9 is a system with the ability to snip out and replace bits of genes, which Myriam has previously blogged about here. Using this approach, they resistant gene could actually snip out the “unresistant” second copy and replace it with a copy of itself.This way, when the modified mosquito passes the resistance gene to its offspring, the unresistant second gene from the other parent gets replaced by another copy of resistant one. As a result, ALL the offspring inherit the malarial resistance (see figure, below). This resistance would then become more and more common, theoretically reducing the incidence of malaria in humans.At present there are no plans to release the resistant mosquitos into the wild however. We are, in effect, forcing genetic changes on an entire species, driving its evolution in a particular direction. This could have very unpredictable ecological consequences, as was emphasised in a warning recently published in the journal Science.Additionally, the technology isn’t quite ready yet, but it is only a matter of time before it is. When it is actually ready, we will be presented with a difficult question: considering how devastating malaria is in sub-Saharan Africa, is it ethical to delay the release of this gene drive because of these ecological concerns?This question obviously doesn’t have a simple answer. It is something governments and the science community will have to thrash out in the coming years.

Should children eat rice cakes?

I’ve seen this story pop up on my newsfeed a few times recently, so I thought I’d have a look and see if there is much to it.It is an article about some new guidelines in Sweden regarding arsenic in rice products. They state that due to high levels of arsenic, some rice products can be harmful to children, and that many of them should be rationed, or even avoided altogether.In case you don’t want to read the rest of this blog post, I’ll give you my take on it first. We are already aware that there are high levels of arsenic in rice products, and the US FDA (Food and Drugs Administration) has been monitoring it for years. Long-term exposure to low levels of arsenic has been associated with various cancers, including those of the kidney, bladder and liver. Some in the press have also reported neurotoxicity in children, but there is little reliable evidence for this in the literature.While the link with cancer may be real, the level and time of exposure required to see such effects would suggest that the Swedish Food Safety Authorities are going overboard with this advice, and the possibility of harm is only in extreme cases. So as always, the key is to exercise moderation in all things.The article reports that the Swedish National Food Agency tested 102 rice products for arsenic levels, and recommended that:

"children should not eat rice or rice products such as rice porridge, rice noodles, or breakfast cereal made of puffed rice, such as Rice Krispies, more than four times a week. And with regards to rice cakes, children should completely avoid these."

This advice is slightly puzzling, as it has been known for a long time that there is inorganic arsenic in much of our food, but particularly in rice products. The US FDA has been monitoring arsenic levels in rice products for the last 25 years. In their most recent tests, they analysed over 1300 products, and found results similar to those in Sweden. However, the FDA did not reach the same conclusions regarding safety, something I will go into more later.Unfortunately there isn’t much advice available as to what constitutes “safe” levels of arsenic in food. There are fairly clear guidelines about arsenic in drinking water, but comparing levels in food to those in water is difficult, so the following should be taken with caution.The World Health Organisation (WHO) recommends a limit of 10ug (10 millionths of a gram) per litre of drinking water. They report that there is some evidence of toxicity if the level is 50 – 100ug per litre, which is 5 – 10 times above their recommended limit. Furthermore, they report that from 10 – 50ug per litre there is a possibility of adverse effects, but that these would be at such a low incidence that they would be difficult to detect.Taking the WHO guidelines as reasonable, small children (aged 5 to 8, who drink around a litre of water per day) can expect to stay healthy ingesting 10ug of arsenic per day from their drinking water. This doesn’t take into account the additional arsenic they get from food. However, let’s go with the WHO and take 10ug per day as the safe dose.Many of the rice products tested contain a significant portion of that. Rice cakes, for example, have 4ug of arsenic, while Rice Krispies have 2.2ug. So if a child was to have rice-based cereal for breakfast, rice for dinner and snack on rice cakes, you can see how they could easily exceed our safe dose.This isn’t a problem if it happens irregularly; however, if a child is getting this dose of arsenic every day, then, using the cautious WHO estimates, there is a small possibility of future problems.As I mentioned above, the US FDA have also been keeping an eye on arsenic in rice products. Their testing has been far more comprehensive than that in Sweden, and their findings have been very similar. However, they do not have the same recommendations as the Swedish National Food Agency. The FDA recommends the following:

"Eat a well-balanced diet. All consumers, including pregnant women, infants and children, are encouraged to eat a well-balanced diet for good nutrition and to minimize potential adverse consequences from consuming an excess of any one food. This advice is consistent with the guidance of the American Academy of Pediatrics, which has long stated that parents should feed their infants and toddlers a variety of foods as part of a well-balanced diet.Consider diversifying infant foods: The FDA recognizes that children routinely eat rice products and that by tradition many infants are fed rice cereal as their first solid food. According to the American Academy of Pediatrics, there is no medical evidence that rice cereal has any advantage over other cereal grains as a first solid food and infants would likely benefit from an array of grain cereals."

In conclusion, it is probably right to say that the levels of arsenic in rice may be a problem for children who eat very large amounts of rice products every day. Feeding children 5 rice cakes per day probably isn't the best idea either. However, recommending an outright ban on rice cakes for children seems very extreme, and un-needed. In moderation, they are a perfectly good snack. Parents have enough to worry about, and if a child is getting a balanced diet, then arsenic should not be another thing on that list.

Why is cancer so hard to treat?

As a cancer scientist, a common question I get is “When are we going to cure cancer?”. It sounds like a simple question, but the truth is pretty complicated.The first thing to point out is that finding a cure for cancer is extremely unlikely. Cancer is an umbrella term for over 200 different diseases (1000s of different diseases if you include sub-types). Although these diseases have many outward similarities (all grow uncontrollably and have the potential to invade and spread), the biological mechanism is different for most cancer types. The simple answer is that we may find cures for various cancers, but each will need their own research and treatment strategies.To understand cancer you have to understand that it is a disease of evolution. Over the past 4 billion years we have evolved from a single celled organism to the dominant mammals on the planet. This process is driven by random alterations and mutations of our DNA. Each of these mutations has the potential to change our genetics. If that change gives an individual an advantage over the rest, then that individual is more likely to survive and to pass the advantage on to his or her offspring. This selective pressure to retain advantageous traits is known as “Natural Selection”.These random changes and mutations can happen every single time a cell divides. Our cells are actually astonishingly efficient at avoiding and correcting mistakes, preventing most events that could result in a tumour. However, trillions of our cells divide every single day, and not all mutations can be caught.Just like in our evolution, if a mutation gives one of your cells an advantage over the other cells, then this cell will survive over the cells around it. For example, if a mutation causes a cell to multiply out of control, it will outgrow those around it and form a tumour. Moreover, tumours can often result from unique combinations of mutations, which will drive their growth in a different ways.If you take a step back and think about that, you can begin to see why a cancer can be so hard to treat. It is a corruption of our own cells, genetically almost identical to healthy ones, similar enough to make it hard to target, different enough to drive the disease. Most drugs we try to use will have difficulty differentiating between cancer and healthy cells, and as a result will cause terrible side effects.To make things even more complicated, as the tumour itself grows it accumulates more and more mutations. Some of these mutations will cause further advantage over other cells within the tumours, and form their own little part of the growth, meaning that the cancer can be made up of many cells that are genetically different.This brings us back to the idea of natural selection: when we find a drug that works for a tumour, we are applying a selective, evolutionary, pressure. If any of the different cells in the cancer allow it to resist the therapy, then that cell will quickly take over, giving rise to a chemo resistant cancer (pictured).Tackling this problem requires an understanding of the various mutations that are causing the cancer to grow. This understanding allows us to design drugs towards these specific mutations, a process we have already started. If we can then recognise what mutations are present in a specific tumour (using techniques like liquid biopsies, which we have written about before), we can use this new generation of drugs to target all of the different mutations present. This may, for the first time, allow us to design a treatment specifically aimed at stopping resistance arising.Vast resources are now being invested in developing these targeted therapies. There already have been some significant successes. For example, breast cancer, lung cancer and melanoma patients can now get different drugs depending on the mutations present in their tumours. It is unlikely that we find one drug that will cure cancer, but research in this direction will help us to refine treatments and ultimately improve patient survival. 

Confused by what you read in the papers?

There are constantly contradictory science news articles in the papers, particularly surrounding our health. Aspirin, milk, breast-feeding, money, sex and pizza have all been reported in the main stream press to both cause and prevent cancer (amongst many other things; this website is well worth a read!).Take, for example, statins. This week it was reported that they can reduce complications after surgery. This may confuse you; didn't the same papers warn us this year that statin use may be killing hundreds? Although, don't statins cure prostate cancer? And make women angry?Statins are the most commonly prescribed drugs in the UK. They are used to lower cholesterol levels, and as such help prevent cardiovascular disease. Sir Roger Boyle, the government’s former National Director for Coronary Heart Disease, claims that statins save 9,000 lives a year in the UK alone (I have been unable to find a source for this claim however, so cannot guarantee its accuracy).However, while it is well established that they are effective in high-risk groups, the evidence for their effectiveness in low-risk groups isn’t as strong. Two papers in 2013 suggested that statin use in low-risk patients did more harm than good, but both of these papers have been heavily criticised, and the authors of both have retracted statements regarding the frequency of side-effects. A large review of the literature confirmed that statins were safe and effective at reducing heart attacks and stroke in low-risk groups, but that the benefits were quite small, and that more could be done through life-style changes than statin prescription.The point of this blog is not to write about the use of statins however; it is to highlight the terrible way in which it is reported. A cursory glance at the infographic above shows how confusing the reporting on statins is. As the graphic shows (click image for expanded view), in the Daily Express alone there has been 15 separate stories about statin use this year, 8 negative and 7 positive. The Daily Express isn't alone in this. The Telegraph had 7 stories (3 positive and 4 negative) and the Daily Mail had a staggering 27 (14 positive and 13 negative).The current consensus is that statins do far more good than harm, however poor reporting such as this causes people to stop taking their medication. This happened in Australia following a documentary into statin use, when an estimated 60,000 people stopped taking their prescription. This almost certainly led to fatalities. Shortly after that, an investigation concluded that the documentary had breached standards of impartiality, and the programme was withdrawn. We have seen the same pattern with vaccine use, among other things.Science is an ongoing process and studies into things such as health must be put in to perspective. Most stories in science need to be seen in context, something which rarely happens in tabloids. Reporting on every little study, regardless of the quality of the study, can leave people with the impression that disagreement within the scientific community is much greater than it actually is. This can lead to problems, as we have seen in climate change and vaccines for example.Science communication and reporting is absolutely vital for generating enthusiasm in science, which itself is essential for progress. The more scientists and engineers we have, the better.Unfortunately, people are too easily persuaded to stop taking their prescriptions, or to stop vaccinating their kids. It is true that there must be some public oversight of health interventions, but the pages of tabloids is not the place for this. Unfortunately, scare stories and testimonies of miracle cures sell papers, so this is a problem that we may unfortunately be stuck with.

Can Wi-Fi make you sick?

A French court recently awarded a disability grant to a woman claiming to suffer from electromagnetic hypersensitivity. Sufferers define this as an illness caused by the radiation given out by everyday objects (Wi-Fi routers, mobile phones and power lines, for example), resulting in a wide range of non-specific symptoms, including headaches, fatigue and irregular heartbeats. There have been several lawsuits in the US from people claiming that their health has been affected by Wi-Fi (unsuccessful so far), and just this week in Massachusetts parents have sued a school, claiming that the Wi-Fi there made their son ill.While sufferers may have very real symptoms, we can be extremely confident that they are not as a result of exposure to electromagnetic radiation, and all reliable evidence suggests that electromagnetic hypersensitivity does not exist as an illness. Many studies have now been conducted to test whether the everyday electromagnetic radiation is causing the symptoms that sufferers display.For example, trials have exposed sufferers to either electromagnetic radiation or not, and tested whether the patients can tell the difference (they can’t), or whether there are increased stress hormones in their blood (there isn’t). Alternatively, study participants’ can be given protective netting designed to shield them from electromagnetic fields, sham netting or no netting, and tested to see if their symptoms get any better when shielded (they don’t).A 2010 review of the literature gathered evidence of 46 published papers on electromagnetic hypersensitivity and stated that the authors were “unable to find any robust evidence to support the existence of (electro-magnetic hypersensitivity) as a biologic entity”. Furthermore, the WHO took into account a staggering 25,000 articles, published over the last 30 years, analysing the biological effects and medical applications of non-ionizing radiation and concluded that “current evidence does not confirm the existence of any health consequences from exposure to low level electromagnetic fields”.The most likely explanation is that these symptoms are caused by the nocebo effect. This is the opposite of the placebo effect, so rather than people feeling better when they think they have been given a treatment, they feel worse when they think they have been exposed to something harmful. The symptoms that they feel may be entirely real, but they are almost certainly psychological. In an experiment carried out in 2013, scientists showed half of their subjects an episode of the BBC series “Panorama,” which alleged that WiFi signals were harmful. They then exposed the whole group to a fake Wi-Fi signal and waited to see who would get sick. The ones who watched the documentary were far more likely to develop electromagnetic hypersensitivity symptoms, providing strong evidence that the nocebo effect plays a large role in this syndrome.The judge in the case in France accepted that the woman’s symptoms prevented her from working, but stopped short of recognising electromagnetic hypersensitivity as an illness. This however hasn’t stopped believers from claiming this as a major breakthrough which proves that it is not a psychiatric illness. It doesn’t help when so many news outlets report so credulously on this story. Unfortunately, this court case has given legitimacy to believers in this syndrome, which could have much wider consequences. An industry has sprung up, selling products that claim to protect people from this harmless radiation, exploiting sick and vulnerable people. Unfortunately, this court case will only make this easier.

Have we explained how acupuncture works?

Acupuncture is a topic that divides people. It is seen by some as a little understood branch of medicine, by others simply as pseudoscience. The theory states that inserting needles at specific points can have effects on almost every ailment, from chronic pain and allergies to irritable bowel syndrome and even stroke. At present, however, there is little reliable evidence that acupuncture works any more than placebo, which makes this article from The Guardian quite unexpected:

Rats help scientists get closer to solving the mystery of acupunctureThe Guardian - 21/07/2015

The title is surprising because this was not a report on acupuncture. The scientists applied an electric current through the acupuncture needles. This technique is called transdermal electrical stimulation and is already used in the clinic to treat chronic pain. The authors, however, call it “electroacupuncture“, and equate it to acupuncture. They are not the same thing, and the conclusions are hence not about acupuncture at all.Scientifically there are many other problems with this study. This was a tiny experiment, with only 7 animals being tested with the “electroacupuncture”. It was not blinded, meaning that the experimenters knew what treatment they were giving to each animal. You may not think that this is an important issue, but consider this: studies on acupuncture in the West yield very mixed results, leading us to believe that the effects are either tiny or non-existent. In China, Japan and Taiwan, where there is a culture of belief, almost every single study shows a positive result. The belief of the experimenter can drastically influence the result of an experiment. Blinding is essential in such studies to overcome this.It is also worth drawing attention to the controls used in this study. The experimenters compare “electroacupuncture” to two controls: sham-acupuncture and no acupuncture. Sham-acupuncture is specifically in place to test for the presence of the placebo effect. Depending on the study, sham-acupuncture can be one of a few things, from inserting the needle at a random point in the body to the use of needles that retract into the sheath, so there is no penetration of the skin at all. In this study, the authors used the insertion of their electric needle at a non-acupuncture point as the sham.Tellingly, the authors did not report any difference between sham-acupuncture and acupuncture. The fact that this isn’t reported, and a look at the data presented in the paper, suggests that there is no difference between their “electroacupuncture” and sham. They only report that “electroacupuncture” seems to be slightly better than the no treatment control. So not only their results are unspectacular, but can be entirely explained by placebo effects. It is worth pointing out that the placebo effect can be extremely powerful, and people can see vast improvements when using any therapy that may not be due to the therapy themselves, but down to the placebo effect. This is why we control for it in trials.This control issue with the study is one that is common with other acupuncture research. It is regular these kinds of studies to see no difference between acupuncture and sham-acupuncture, and rather than conclude that acupuncture doesn’t work, they conclude that both acupuncture and sham-acupuncture work, and this is just not true! If a drug had the same level of effect as a sugar pill, we wouldn’t conclude that both are working. Unfortunately, it is rare for studies into pseudoscience to hold themselves to the same standards.Put simply, this is a badly designed study, from which the authors conclude that acupuncture works, seemingly without actually looking at acupuncture at all. At present, we cannot even say that there is a “mystery of acupuncture”, as described in the headline of this article. There is no mechanism in science or medicine through which sticking needles into particular points around the body can have very specific effects on other parts, so to claim acupuncture works would require convincing evidence (extraordinary claims require extraordinary evidence). This is certainly not that.