Heroes Not Zombies

In an excellent article in the BMJ, Nicholas A Christakis, professor of medical sociology at Harvard, asks the questions all doctors (and their patients) should be asking. He points out that too often these days we misunderstand (or maybe misuse) the results from drug trials.

Doctors say that a drug “works” if, in comparison with the control arm of a clinical trial, significantly more people in the treatment arm respond. Unfortunately, this is a naive oversimplification, and it breeds complacency among patients and physicians alike

He points out that it is frequently the case that a drug which is shown in trials to help more patients than a placebo or other treatment, very often actually only delivers this benefit for the minority of patients who are actually prescribed it. I’ve quoted Dr Roses of GlaxoSKF a few times on that same point!

Countless drugs that have been shown in randomised controlled trials to be effective work in only a minority of patients. Imagine that a drug worked 20% of the time in a trial, compared with 5-10% for a placebo. This is the case for drugs ranging from antihypertensives to minoxidil to cancer chemotherapy. Such a difference in a trial corresponds to an enormous effect size. However, most patients taking such drugs would not benefit—they would hardly think that the drugs “worked.” If you buy a toaster you expect it to be able to toast bread every time it is used. If it does not, you say it does not work and return or discard it. You do not take solace from the claim that, in fact, 30% of the time in the manufacturer’s laboratory the toaster did a better job in browning bread than sunshine alone.

It does amaze me that certain treatments are labelled “proven” in this way. What’s even worse though is when the prescribing doctor then seems to blame the patient for their “failure” to respond to the treatment. This leads me on to the author’s recommendation –

one appropriate reaction is to have a protocol of administration that evaluates a patient’s response. Doctors sometimes already do this in a systematic way (such as when titrating the administration of highly active antiretroviral treatment). But this practice should be more widespread and more formal

Whilst I agree with this recommendation, it still does amaze me. Don’t all doctors routinely check how every individual patient is doing?

Anyway, here’s the take home message, in the last paragraph of the article –

Just because drugs work in trials does not mean they will work in our patients. In fact, we can often expect that they will not work at all.

There’s quite a trend in recent years towards Public Health measures centred around what you might call “technical fixes” – the idea that a technology of some kind can improve health. The technology of choice, of course, is pharmacology and we are bombarded with messages that various different drugs should be taken by increasingly large proportions of the population in order to achieve greater Public Health. I think this is a myth. It’s part of the larger myth that science and technology will allow us to control Nature, to set out how we would like life to be and to achieve those goals. There’s an awful lot of sloppy thinking on this subject. Quite often we are told that a particular drug has the ability to be “life saving”. Drugs don’t save lives. At best they alter the death experience, but everybody dies from something and drugs actually don’t let you be sure that YOU, the individual YOU, can avoid a certain kind of death.

Take death from heart disease and strokes for example. We’ve been told that everyone should take aspirin because if everyone took aspirin then a lot less people would die from heart attacks or strokes. Listen carefully to that advice because it is a statistical statement – if MOST people took drug x then LESS people would die from y. That’s not the same as saying that if YOU took drug x then YOU would be less likely to die from y. The difference might seem subtle but it’s significant. The difference is ignored by people who suggest that we are all the same and we should all follow the same course of action. For example, a few years back some doctors and scientists promoted the idea of a “polypill” which every adult should take so that the death rate from certain diseases would be reduced. (what the authors didn’t seem to think about was what, if they were correct, would all these people die from instead? Don’t you think that matters?)

In this week’s BMJ there is an editorial summarising the studies of populations taking aspirin and their conclusions are clear.

These result support the concept that risk assessment alone cannot predict which patients will benefit from aspirin. In fact, the only predictor of clinical response to aspirin is a history of a major coronary or cerebral ischaemic event, as defined by the previous meta-analysis

In other words, there is only a statistical benefit from aspirin in patients who have already experienced coronary or cerebral ischaemic disease (that’s angina, heart attacks or strokes primarily). In the population who haven’t experienced one of these diseases there’s no benefit from taking aspirin.

Buried in the text of the article is this statement too –

However, not all patients with cardiovascular disease respond to aspirin, as shown by a recent meta-analysis of aspirin trials in peripheral artery disease

So beware of taking these messages at face value. It seems that only those who have already developed cardiovascular disease may be helped by taking aspirin and of these not all will get the benefit.

I’ve wrestled with trying to understand what health is – in fact, I often challenge doctors I teach to come up with a definition of health which makes no reference to disease or illness. Sure, WHO’s definition does say that health is more than the “mere absence” of disease, but that still doesn’t quite capture it. I think the three qualities of adaptability, creativity and engagement are good ones to consider when grappling with this concept called health.

But there’s another word doing the rounds now – “wellness”. Was does “wellness” mean to you, and does it mean something that “health” doesn’t?

Whatever definitions you come up with, I bet it doesn’t include what I just read about a new technology – a test card which, using a single drop of saliva or blood, can check for the presence of a bank of diseases.

I’m sorry, but that’s a “sickness card” not a “wellness card”! Even if it could test against 20 diseases, it will only tell you that you don’t have one of those 20 diseases – and that does not make you “well”!