Some questions puzzle me, and I search for the answer. For a number of years I am trying to establish. ‘What is T?’ My wife helpfully remarked that it is a drink with jam and bread. Ho, ho.
Moving swiftly on. My question relates to the concept of Number Needed to Treat (NNT). The NNT is a figure widely used in medicine as an outcome measure. It means how many people do you need to treat ‘T’ to achieve a benefit of some kind. The benefit can be many different things, for example: pain relief, curing a chest infection, improving pain and mobility following a hip replacement.
In these cases the ‘T’ is pretty clear cut. You have a medical problem and you intervene in some way to make it better, or cure it. But what is the ‘T’ when you are in the world of preventative medicine? If you are trying to stop something happening e.g. a heart attack, stroke, pulmonary embolism, or death, can you call preventing such things a form of ‘treatment?’
In reality, in preventative medicine, the ‘T’ turns into something else. It has become ‘P’, as in prevent. But treating and preventing are not the same thing, and you can’t use them interchangeably.
If you have a chest infection and I give you antibiotics then I have, in most cases, treated the infection. On the other hand, if you have a high blood pressure and I ‘treat’ it, all I have done is the lower the blood pressure. I have not immediately done anything else. A high blood pressure causes no symptoms, and there is nothing to be treated – other than future risk.
In fact, if lowering the blood pressure were a form of treatment, the NNT would be very nearly one, in that I will lower the blood pressure in almost every case where I prescribe a drug. But the NNT does not refer to the effect on blood pressure lowering; it refers to the number of people you need to treat to prevent, say, a stroke, by lowering the blood pressure.
As I hope is clear, in preventative medicine, the NNT should really be the NNP.
So what, you may think. Everyone working in this area knows that the NNT is really an NNP. You just need to know that when we use the term NNT, we are really talking about the number needed to treat to ‘prevent’ an event. Yes, this is true. However, the underlying problem with nomenclature does not disappear if we change NNT to NNP. The focus simply shifts to the word prevent itself. To prevent something means to stop it happening – forever.
Now, let us imagine death.
Can we prevent death? No, clearly we cannot. We do not make people immortal by lowering their blood pressure. All we can do, the very best we can possibly do, is to increase life expectancy – by some amount. Which means that prevention does not actually mean prevention. When we look at death as an outcome, prevention can only mean life extension. Or, turning this the other way round, the amount of time by which we delay something from happening.
At this point, I hope it has become clear that ‘T’ in preventative medicine has almost nothing to do with ‘treating.’ We treat nothing, we prevent nothing, we simply delay. At least that is all we can do with death. It is possible that we may prevent things such as non-fatal strokes, although we don’t really know, because we do not usually follow people up for long enough to be certain.
Why is this important? It is important for the following reason. When many clinical trials finish, and there is a difference in the number of deaths between the treatment and placebo arm, it is claimed that the difference represents lives that have ‘been saved.’ Which is another way of saying that death has been prevented which is, in turn, a different way of saying that death has been treated. NNT.
To give an example of how this work in real life I shall switch to statins and the Heart Protection Study (HPS)
Heart Protection Study
This graph shows the ‘mortality’ curves for the statin and placebo arms. At the start of the trial everyone is alive, 100% in both groups. Five years later, the end of the study, 92.6% of those in the statin arm were still alive, and 90.8% of those in the placebo arm were still alive. A difference of 1.8%.
This was presented, in the HPS press-release, as follows:
‘In this trial, 10 thousand people were on a statin. If now, an extra 10 million high-risk people worldwide go onto statin treatment, this would save about 50,000 lives each year – that’s a thousand a week.’ http://www.ctsu.ox.ac.uk/~hps/pr.shtml
This is a very clear statement. Treat ten million people, and you will save 50,000 lives per week. But are these lives actually saved. No, of course not. Below, I have re-drawn the graph and extended both ‘survival’ lines by a year. We now have a year six.
As I hope is clear, by year six, if we assume the lines continue along their previous trajectory, every single extra person who was alive in the statin arm, compared to the placebo arm, is now dead. Thus 1.8% of people did not have their lives ‘saved’. In fact, the average increase in survival time for these 1.8% was approximately six months. [Half of the 1.8% would have died after six months, which give you the mean/average].
So what is ‘T’ in this case. It is certainly not treatment, prevention, or number needed to treat to prevent death. Nor is it 1.8% of lives saved. It is a life extension of six months, for 1.8%.
Or, to put this another way. If you treat one hundred people at very high risk of heart disease (secondary prevention) with statins, what you are achieving is the following:
• 1.8 will live, on average, an extra 6 months.
• 98.2 will gain no benefit
What is ‘T?’ What indeed. Not perhaps what you first thought. T, at present, is taken to mean treatment. With preventative medicine treatment is taken to mean prevention, and prevention is taken to mean lives saved. But you cannot save a life, all you can do is extend life.
So, when someone says….
‘In this trial, 10 thousand people were on a statin. If now, an extra 10 million high-risk people worldwide go onto statin treatment, this would save about 50,000 lives each year – that’s a thousand a week.’
…they are talking nonsense.
In very short summary. NNT is a widely used treatment outcome, and it guides both clinical and economic decisions on what drugs should be used, or not used. It is a pity that in preventative medicine, NNT is meaningless, because ‘T’ has no value attached to it. Indeed, it might as well be a drink with jam and bread.