How improved cancer screening can make us think we are doing better than we really are

This blog post is a follow on from this post I wrote about cancer survival, and is about some really interesting quirks we encounter when we try to study it. These problems arise when we increase our ability to detect the cancer at earlier stages.

Lead time bias 

The first of these is known as lead time bias. Because of better technology, we can now diagnose cancer earlier. So imagine a case where a new screening technique lets us catch a cancer 1 year earlier. The catch is that no matter how early we catch it, in this case the disease is going to progress and ultimately kill the patient.So before the introduction of this new technology the patient might only survive 1 year after diagnosis, because we are catching it late. After the introduction, we can now catch the disease early, and the patient will survives 2 years after diagnosis.If we were just looking at the numbers, we might think that we are making significant progress with this disease, because patients are now surviving for 2 years rather than just 1. However, we have done nothing to increase the patient's lifespan. If we hadn’t caught it at all, the patient would have died on the same day.This is known as lead time bias. Because we are catching a disease earlier, it can look like patients are surviving longer, when in fact they are not. It is an easy mistake to make, but a very important bias to consider when we are talking about cancer survival.

Length time bias 

The second problem appears when you realize that if we detect a cancer early, it is possible that we are detecting a cancer that might never have progressed at all. It isn't well-known, but there are cancers that never progress to a dangerous level. If we look at autopsies, nearly half of all men have prostate cancer when they die. However, only a small proportion of them actually die from prostate cancer. The rest have the cancer, but it will never progress. So the men are dying with prostate cancer, but not from prostate cancer. Most of these men will never have symptoms, so will never be diagnosed.If a patient has symptoms, then it is quite likely that the cancer will progress if we don't treat it. However, if we use a screening technology and catch the cancer before symptoms appear, then it is possible (likely) that some of those cancers were never going to progress to a dangerous level.For example, before a screening technology is developed, survival from a particular cancer might be quite low, because we don't detect the cancer until symptoms appear. Then we develop the new screening technology, and suddenly we are detecting all the cancers, regardless of whether they have symptoms or not.If we were just looking at the numbers it would look like the incidence of that cancer is increasing (we now detect extra cancers that we wouldn’t have before), but it would also look like we are successfully treating these additional patients. Even though those cancers would never progress, patients would still get (un-needed) chemotherapy, and it would look like the treatment was successful.The result of this is that we would think that the survival is increasing, but in reality, we are just identifying cancers who we wouldn’t have previously.This is just two examples, but understanding this kind of bias helps us realise just how easily we can be fooled into thinking the wrong thing. This lets you look more critically at studies, and hopefully means we are less prone to bias when carrying out these kind of studies.

Cancer vaccine breakthrough?

Every once in a while I see a paper that makes me sit up and say “Wow”. They are rare, but when they happen they let us really see the progress that is being made. This week one of those papers was published in the journal Science Translational Medicine.The study built on recent work that is focused on the immune system, and the potential that we can make it attack a cancer (something which doesn’t normally happen). There has already been some excellent results in this field in human trials, but this study took the work in a slightly different direction. The work was carried out in mice, so is still at an early stage, but the a small clinical trial is starting this month, and that will tell us how optimistic we should be.What these scientists have developed is a clever way to activate the immune cells specifically within the tumour by injecting it with a tiny amount of DNA and another compound. When they did this they found that the tumours shrank and disappeared. It gets better though: they tried the same approach in breast cancer, colon cancer, and melanoma, (three very different cancer types) and saw the same effect across the board.Perhaps the most exciting part of the work was that when they injected one tumour, the immune system attacked all the tumours in that mouse, which means that this is an approach that may work in late stage patients, who are typically very difficult to treat.The technique itself makes use of a trick that is already used in patients: by injecting a tiny amount of DNA into a patient’s cancer, we can improve responses to chemotherapy. It works by making the immune cells in the vicinity express a marker on their surface, which has the effect of priming them for action. The insight that these scientists had, was that by using a second compound to recognize this marker, they could activate the cells to attack the tumour. Because the injection is directly into the cancer, only the immune cells that recognize the tumour are activated. Some of these then leave the original tumour and attack other ones throughout the body.This approach proved to be remarkably effective. In total, the scientists treated 90 animals with the therapy. Eighty seven of those were cured. Additionally, in some of the mice the tumours became resistant and began to grow again, which is typically what happens in human patients. However, if they then injected this new tumour with the therapy, they saw the same shrinking as before, which is extremely encouraging.It was a startlingly successful study, but as I mentioned above, this work was in mice, so we can’t be sure the results will translate to humans. It’s possible that there will be toxicity to humans, or that there will be issues with stimulating the immune system like this, but it is also very possible that we will see some real benefits of this therapy.It’s an exciting time to be in cancer research!

Is coffee bad for you?

People have an undying love for coffee. Around the world, it’s estimated that 2 billion cups are drank every single day. Lots of people can’t start the morning without one, and there’s now a coffee shop on every corner in every city. Considering this popularity, it is perhaps unsurprising that the health benefits/health damaging effects of coffee are never far from the news. This year alone has seen 25 different articles on the Daily Mail Online, detailing why the drink is going to make you live longer or shorter, depending on the article. Of those 25, 14 were extolling the benefits of coffee, while 11 were describing the opposite.On one particularly impressive week the site published six separate articles on the topic, claiming among other things that coffee is nature’s Viagra, that it protects against liver cancer, and that it can cause miscarriage and birth defects. If you were to ask somebody whether coffee was good or bad for them, I sincerely doubt that they would know. So what does the evidence say?Quite a lot actually. There have been many studies on the role that coffee may play in different diseases, which I will get in to below. As is almost always the case however, the first thing to say is that there’s probably no need to change your habits. Whether coffee is good for you or bad for you, the effect seems to be minor. If you love your coffee, there’s no need to cut back. If you’re not a drinker, there’s no need to start.Before I get into the health implications of coffee, it is worth mentioning that aside from the drink itself, people should really think about the way they drink their coffee. It is thought that at least 58 billion paper cups are thrown away each year, made from 32 million trees, and requiring a staggering 100 billion litres of water for their production. It is an extraordinarily wasteful industry, and something as simple as buying a reusable cup can make a significant difference, particularly if it is not made from plastic.Below I have described what the current literature has to say regarding coffee consumption and various diseases. Ultimately, it is safe to say that for a healthy person with no underlying conditions, normal coffee consumption is probably good for you. The benefit is small in all cases, so it is not something to worry about. As always, there are caveats involved (whether you take sugar in your coffee, whether you drink decaffeinated, how hot it is when you drink it…), but I have tried to answer the major questions below. It is worth pointing out that although an individual coffee drinker is unlikely to see any benefit from their habit, due to the large number of drinkers around the world coffee drinking could potentially have a large impact on the overall health of the population.

Ultimately, it is safe to say that for a healthy person with no underlying conditions, normal coffee consumption is probably good for you.

Q: How much coffee is too much?In general, various safety authorities suggest that 2 – 3 cups of coffee in one sitting is perfectly fine, provided that people don’t drink much more than 6 in a day. For most people, 8 – 10 cups will begin to produce negative side effects, including migraine, anxiety, nervousness, trembling, insomnia and an increased heart rate. These side effects are all caffeine related, and this seems to be the main culprit in the coffee-related problems. Obviously the amount of caffeine differs in different coffee brands and brews, and the numbers above relate to roughly one shot of espresso per cup. There has not been any study confirming or refuting long-term detrimental side effects of regularly drinking more than 6 cups per day (apart from extreme cases when people far exceed this), so we can’t really say either.A: 6 cups seems to be the recommended daily limit for a healthy person, but this is largely precautionary. Q: Does coffee change your risk of dying?The simplest thing we can look at is whether coffee makes you live longer. There have been numerous studies into this, and their results have been mixed. It is pretty clear that coffee doesn’t in general shorten life. Several studies have found no correlation between coffee consumption and longer life, however some have found the opposite. The most recent work I could find suggests that those drinking more than 4 cups a day were at a lower risk of dying, however this was only true in people over 45 years of age. This work was presented at a conference and has yet to be published, so I haven’t been able to have a look at their analysis. However, confusingly, other studies have found that those who drink small amounts of coffee (1 cup a day) get a benefit, but that benefit disappears if you drink more than 4 cups. Some studies claim that women benefit more than men, and others that the benefits depends on what ethnic group is being studied. All in all, the literature is mixed, which is a clear sign that if there is an effect, it is a tiny one. It is interesting to note though, that the scientists who carried out the most recent study found that even people who drank decaffeinated coffee got some of this benefit, meaning that the effect may only partially be as a result of caffeine intake.A: Coffee may extend life in certain circumstances, but if it does, the effect is tiny. Q: Are coffee and cancer associated?As coffee drinking and smoking often went hand in hand in the past, it is difficult to separate the two in studies. What is clear is that the results are mixed. A Japanese study suggested that high coffee consumption (over 5 cups a day) had a protective effect. Another recent analysis suggested that coffee is not associated with the large majority of cancers, with a few exceptions. Coffee seems to have a protective effect against liver cancer, but the size of this effect is debatable. However as most liver cancers are related to either smoking or obesity, there are far bigger interventions that can be made to protect against this cancer. There have been studies showing a slightly reduced incidence of endometrial, skin, gallbladder, oral, and kidney cancer in coffee drinkers, but these studies have yet to be confirmed. Finally, there was a suggestion that coffee drinkers were more prone to prostate cancer, but recent studies have cast doubt on this.A: Coffee seems to have a protective effect against liver cancer, and potentially against several others. Q: Does coffee affect heart health?It was thought for a long time that coffee was associated with cardiovascular diseases, hypertension, and heart failure. This makes intuitive sense; when people have too much coffee, they often feel like their heart is racing. Several studies seemed to show this was the case, however none of the studies were thorough enough to tell for sure. More recent studies have shown that this is not the case, and that coffee has either a neutral or a beneficial effect on heart health. For example, some studies show that coffee is protective against coronary heart disease in women, and reduces the risk of death in patients who have had a heart attack. Other studies show no change or an increase in coronary heart disease risk, so any effect is likely to be small.A: Coffee has a neutral or slightly beneficial effect on heart health. Q: How about the effect of coffee on mental health?The number of studies looking at this is smaller than in the previous paragraphs. However, those that have been done do show that coffee has a slight protective effect on depression risk, although some of those studies were of poor quality. Due to the sleep disturbing effects of excess caffeine, there is reason to think that this may also have a detrimental effect on mental health, but the evidence has not backed this up.A: Coffee seems to have a slight beneficial effect on mental health Q: Does coffee play a role in neurodegenerative diseases like Alzheimer’s and Parkinson’s?Lifelong coffee consumption seems to have a protective effect on the development of Alzheimer’s and Parkinson’s. In both cases the effect was more pronounced in the early stages of the disease, and in the case of Parkinson’s, it the effect was bigger in men than in women.A: Long-term coffee drinking has a slight protective effect in age-related dementia Q: Does coffee protect your liver?It is in liver disease that we see the biggest protective effect of coffee. Liver enzymes tend to be lower in coffee drinkers (which is a good thing). Interestingly, this tends to be more pronounced in patients at the highest risk of liver disease, such as alcoholics. It is also beneficial in non-alcoholic liver disease and other metabolic syndromes. Coffee inhibits the Hepatitis C virus, and drinkers show lower levels of damage in their livers, and as mentioned above, coffee seems to have a protective effect against liver cancer.A: Coffee has a slight but significant protective effect against almost all kinds of liver disease and damage Q: Does coffee affect fertility?There is very little evidence that coffee consumption has a measurable effect on fertility. Several studies have shown a slight decrease in semen quality with high caffeine intake, and others show a very slight increase in the time to pregnancy for caffeine drinkers. This study included energy drink consumption have far higher levels of caffeine than coffee, so the results were probably skewed by that population. Several larger studies have found no correlation between coffee consumption and an increased time to pregnancy.A: Coffee drinking does not decrease fertility. Q: Is coffee safe in pregnancy?Many women avoid caffeine during pregnancy, preferring to err on the side of caution in this case. The WHO recommends limiting caffeine intake during pregnancy to 3 cups or fewer per day, and the evidence supports this conclusion. Studies have shown that high caffeine intake is associated with a slightly higher risk of pregnancy loss and developmental defects. If drinking fewer than 3 cups per day however, there is no evidence of an increase in foetal malformation, neurodevelopmental defects, or miscarriage.A: High coffee consumption may cause issues in pregnancy, but no problems have been seen for those drinking 1 – 2 cups per day.

Using stem cells to treat cancer

There are many scam artists around nowadays proclaiming the benefits of their particular unproven stem cell therapy, for anything from curing cancer to making paralysed people walk again. It’s not surprising really; stem cells are a pool of cells in every organ that are almost eternally youthful and can regenerate themselves and all other cells in the organ. They sound almost magical. However, last year the FDA (the US Food and Drug Administration) had to move to crack down on these clinics, citing the of lack of evidence that any of them work and a number of serious complications reported following treatment. Complications including patients in Florida dying, a woman developing bone fragments in eyelids following a stem cell facelift, and another developing nasal tissue in her spine after a doctor promised to cure her paralysis with stem cells.It is a field ripe for abuse partly because it is one with so much potential. Stem cells do have fascinating possible applications, and there is a lot of research going in to them at the moment. Unfortunately, most exposure people have with them is in science fiction or alternative medicine. Which is why it was very interesting to see a study published last week that underlined how much real potential this field of research has. The study used mice instead of humans, so is still at an early stage, but is very promising nonetheless.Scientists from North Carolina were studying a deadly form of brain cancer called glioblastoma (GBM), which has extremely poor prognosis for patients diagnosed with it. The work builds on the bizarre finding that these tumours somehow attract stem cells to them. So if you look at a GBM in humans, there are stem cells inside them that shouldn't be there. Scientists had previously used this fact to load some stem cells with chemotherapy and could show that in mice, the stem cells were attracted by the tumour as expected, but they could also release their therapy while they were there. The problem with this is that we have very few stem cells in the brain so finding them and loading them with drugs is very difficult.In this case the scientists overcame that problem by turning skin cells into brain stem cells. They took skin cells from mice into the lab and, because skin cells originally comes from the spinal cord which is technically part of the brain, were able to trick them into reverting back into that state. They could then give these cells their chemo payload and inject them back into the mice. When they did this the stem cells made their way to the brain and reduced tumour size to almost nothing, which is obviously a very impressive response.There are two key advantages of this approach: 1) we have lots of skin stem cells, so they are easy to get; and 2) you can do it with a patient’s own cells, meaning that you wouldn’t have to worry about rejection, which can cause severe complications. This work still has to undergo significant testing to ensure it is safe for humans, but studies so far have been positive. A group in California have carried out a clinical trial which showed that apart from tissue rejection (which isn’t an issue in this case), stem cells can be a remarkably safe form of therapy.This work is still at an early stage, but it is very encouraging. Considering that the average survival time for a patient with GBM is only a year, any new therapeutic avenues are welcome. The stem cell field is one that is on the cusp of large-scale application, and this could be one of the first in an array of new therapies for cancer and many other diseases. At present however, 95% of clinics offering these therapies are charlatans looking to make money off vulnerable people.

What happens when we don't publish clinical trials

The last blog I posted emphasised the importance of publishing all clinical trials. The story of Lorcainide is a stark warning of what happens when we don’t.In 1980 a cardiologist in Nottingham named Alan Cowley carried out a small clinical trial of a drug called Lorcainide. It was known at the time that heart attacks could cause irregular heartbeats in patients (known as arrhythmia), and these arrhythmias often lead to early death. Lorcainide had been shown to suppress arrhythmia, so it made sense that patients who came to hospital with a heart attack should be treated with the drug. Cowley and his colleagues carried out a small trial with 95 patients, and tested them to see whether they were getting more or fewer arrhythmias. The drug worked, lowering the frequency of serious arrhythmia.The doctors noticed something else however. Of the 48 patients on the drug, 9 had died, compared to only 1 patient on the placebo. This was a very small trial, so the doctors weren’t overly alarmed. It’s not surprising that 10 patients died in the study; these are patients who are presenting with heart attacks after all. It was just worrying that there was such an imbalance between the groups. The doctors chalked it up to bad luck, and viewed their trial as a success.At the time, this was a perfectly valid opinion. The study had been designed to analyse arrhythmias, not look at mortality. Furthermore, it was a tiny study, so they were justified in assuming the increased death was down to chance. Unfortunately however, what happened next ensured that the importance of this study would not be recognized.The doctors wrote an article describing their findings and tried to get it published. They submitted it to three different journals, but without success.  At the same time, the company that made Lorcainide decided to discontinue it (for unrelated commercial reasons), so the doctors lost interest and decided not to publish their results.To be clear, they were trying to publish the study as a success. Lorcainide was able to decrease serious arrhythmias after a heart attack. But within the paper was the information about increased mortality, and this would have been noticed. If it had been published, the study may not have prevented prescription, but it would certainly have suggested the need for further study.Although Lorcainide was never brought to market, other similar anti-arrhythmia treatments were prescribed to heart attack patients throughout the 80s. However, in 1983 there was a review of the available literature that proposed that there was no benefit in using these drugs. The authors of that study actually suggested that there might even be increased death following treatment, but this harmful effect was too small to be sure it was real.In hindsight it is clear that this small effect on mortality was in fact bigger than was realised. That study looked at published data to come to their conclusion. However, they were missing an important clinical trial, one that was in fact sitting unpublished on a hospital desk. If they had access to this data, they may have come to a different conclusion, flagging up the danger years earlier than it was.Towards the end of the decade, after more trials were published, two studies were carried out, both of which suggested that these drugs were doing more harm than good. At this point the danger was realised, and prescriptions dropped. However, it is estimated that 20,000 to 75,000 people died every year because of the use of anti-arrhythmia medication.In 1993, 13 years after it was originally carried out, the clinical trial on Lorcainide was published. The authors pointed out that it was perfectly reasonable to assume the increased death was a matter of chance, and they are probably correct in that. Unfortunately, when they decided not to publish and leave their study to gather dust, they contributed to an unfolding tragedy. At the time, the need to publish all trials regardless of their results wasn’t appreciated, so whether they can be blamed for what happened is a difficult question. What is certain however is that as a result of not publishing hundreds of thousands of people died.Well carried out clinical trials are the bedrock of modern medicine, and unbelievably, we are still in a ridiculous situation where reporting and publishing of trials is patchy at best. Until this situation is corrected we are at risk of another catastrophe like Lorcainide. Sign the AllTrials petition here to register your support for reform.

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.

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.