Читать книгу Bad Science - Ben Goldacre - Страница 24

So four pills are better than two: but how can this be? Does a placebo sugar pill simply exert an effect like any other pill? Is there a dose-response curve, as pharmacologists would find for any other drug? The answer is that the placebo effect is about far more than just the pill: it is about the cultural meaning of the treatment. Pills don’t simply manifest themselves in your stomach: they are given in particular ways, they take varying forms, and they are swallowed with expectations, all of which have an impact on a person’s beliefs about their own health, and in turn, on outcome. Homeopathy is, for example, a perfect example of the value in ceremony.

I understand this might well seem improbable to you, so I’ve corralled some of the best data on the placebo effect into one place, and the challenge is this: see if you can come up with a better explanation for what is, I guarantee, a seriously strange set of experimental results.

First up, Blackwell [1972] did a set of experiments on fifty-seven college students to determine the effect of colour—as well as the number of tablets—on the effects elicited. The subjects were sitting through a boring hour-long lecture, and were given either one or two pills, which were either pink or blue. They were told that they could expect to receive either a stimulant or a sedative. Since these were psychologists, and this was back when you could do whatever you wanted to your subjects—even lie to them—the treatment that all the students received consisted simply of sugar pills, but of different colours.

Afterwards, when they measured alertness—as well as any subjective effects—the researchers found that two pills were more effective than one, as we might have expected (and two pills were better at eliciting side-effects too). They also found that colour had an effect on outcome: the pink sugar tablets were better at maintaining concentration than the blue ones. Since colours in themselves have no intrinsic pharmacological properties, the difference in effect could only be due to the cultural meanings of pink and blue: pink is alerting, blue is cool. Another study suggested that Oxazepam, a drug similar to Valium (which was once unsuccessfully prescribed by our GP for me as a hyperactive child) was more effective at treating anxiety in a green tablet, and more effective for depression when yellow.

Drug companies, more than most, know the benefits of good branding: they spend more on PR, after all, than they do on research and development. As you’d expect from men of action with large houses in the country, they put these theoretical ideas into practice: so Prozac, for example, is white and blue; and in case you think I’m cherry-picking here, a survey of the colour of pills currently on the market found that stimulant medication tends to come in red, orange or yellow tablets, while antidepressants and tranquillisers are generally blue, green or purple.

Issues of form go much deeper than colour. In 1970 a sedative—chlordiazepoxide—was found to be more effective in capsule form than pill form, even for the very same drug, in the very same dose: capsules at the time felt newer, somehow, and more sciencey. Maybe you’ve caught yourself splashing out and paying extra for ibuprofen capsules in the chemist’s.

Route of administration has an effect as well: salt-water injections have been shown in three separate experiments to be more effective than sugar pills for blood pressure, for headaches and for postoperative pain, not because of any physical benefit of salt-water injection over sugar pills—there isn’t one—but because, as everyone knows, an injection is a much more dramatic intervention than just taking a pill.

Closer to home for the alternative therapists, the BMJ recently published an article comparing two different placebo treatments for arm pain, one of which was a sugar pill, and one of which was a ‘ritual’, a treatment modelled on acupuncture: the trial found that the more elaborate placebo ritual had a greater benefit.

But the ultimate testament to the social construction of the placebo effect must be the bizarre story of packaging. Pain is an area where you might suspect that expectation would have a particularly significant effect. Most people have found that they can take their minds off pain—to at least some extent—with distraction, or have had a toothache which got worse with stress.

Branthwaite and Cooper did a truly extraordinary study in 1981, looking at 835 women with headaches. It was a four-armed study, where the subjects were given either aspirin or placebo pills, and these pills in turn were packaged either in blank, bland, neutral boxes, or in full, flashy, brand-name packaging. They found—as you’d expect—that aspirin had more of an effect on headaches than sugar pills; but more than that, they found that the packaging itself had a beneficial effect, enhancing the benefit of both the placebo and the aspirin.

People I know still insist on buying brand-name painkillers. As you can imagine, I’ve spent half my life trying to explain to them why this is a waste of money: but in fact the paradox of Branthwaite and Cooper’s experimental data is that they were right all along. Whatever pharmacology theory tells you, that brand-named version is better, and there’s just no getting away from it. Part of that might be the cost: a recent study looking at pain caused by electric shocks showed that a pain relief treatment was stronger when subjects were told it cost $2.50 than when they were told it cost 10c. (And a paper currently in press shows that people are more likely to take advice when they have paid for it.)

It gets better—or worse, depending on how you feel about your world view slipping sideways. Montgomery and Kirsch [1996] told college students they were taking part in a study on a new local anaesthetic called ‘trivaricaine’. Trivaricaine is brown, you paint it on your skin, it smells like a medicine, and it’s so potent you have to wear gloves when you handle it: or that’s what they implied to the students. In fact it’s made of water, iodine and thyme oil (for the smell), and the experimenter (who also wore a white coat) was only using rubber gloves for a sense of theatre. None of these ingredients will affect pain.

The trivaricaine was painted onto one or other of the subjects’ index fingers, and the experimenters then applied painful pressure with a vice. One after another, in varying orders, pain was applied, trivaricaine was applied, and as you would expect by now, the subjects reported less pain, and less unpleasantness, for the fingers that were pre-treated with the amazing trivaricaine. This is a placebo effect, but the pills have gone now.

It gets stranger. Sham ultrasound is beneficial for dental pain, placebo operations have been shown to be beneficial in knee pain (the surgeon just makes fake keyhole surgery holes in the side and mucks about for a bit as if he’s doing something useful), and placebo operations have even been shown to improve angina.

That’s a pretty big deal. Angina is the pain you get when there’s not enough oxygen getting to your heart muscle for the work it’s doing. That’s why it gets worse with exercise: because you’re demanding more work from the heart muscle. You might get a similar pain in your thighs after bounding up ten flights of stairs, depending on how fit you are.

Treatments that help angina usually work by dilating the blood vessels to the heart, and a group of chemicals called nitrates are used for this purpose very frequently. They relax the smooth muscle in the body, which dilates the arteries so more blood can get through (they also relax other bits of smooth muscle in the body, including your anal sphincter, which is why a variant is sold as ‘liquid gold’ in sex shops).

In the 1950s there was an idea that you could get blood vessels in the heart to grow back, and thicker, if you tied off an artery on the front of the chest wall that wasn’t very important, but which branched off the main heart arteries. The idea was that this would send messages back to the main branch of the artery, telling it that more artery growth was needed, so the body would be tricked.

Unfortunately this idea turned out to be nonsense, but only after a fashion. In 1959 a placebo-controlled trial of the operation was performed: in some operations they did the whole thing properly, but in the ‘placebo’ operations they went through the motions but didn’t tie off any arteries. It was found that the placebo operation was just as good as the real one—people seemed to get a bit better in both cases, and there was little difference between the groups—but the most strange thing about the whole affair was that nobody made a fuss at the time: the real operation wasn’t any better than a sham operation, sure, but how could we explain the fact that people had been sensing an improvement from the operation for a very long time? Nobody thought of the power of placebo. The operation was simply binned.

That’s not the only time a placebo benefit has been found at the more dramatic end of the medical spectrum. A Swedish study in the late 1990s showed that patients who had pacemakers installed, but not switched on, did better than they were doing before (although they didn’t do as well as people with working pacemakers inside them, to be clear). Even more recently, one study of a very hi-tech ‘angioplasty’ treatment, involving a large and sciencey-looking laser catheter, showed that sham treatment was almost as effective as the full procedure.

‘Electrical machines have great appeal to patients,’ wrote Dr Alan Johnson in the Lancet in 1994 about this trial, ‘and recently anything to do with the word LASER attached to it has caught the imagination.’ He’s not wrong. I went to visit Lilias Curtin once (she’s Cherie Booth’s alternative therapist), and she did Gem Therapy on me, with a big shiny science machine that shone different-coloured beams of light onto my chest. It’s hard not to see the appeal of things like Gem Therapy in the context of the laser catheter experiment. In fact, the way the evidence is stacking up, it’s hard not to see all the claims of alternative therapists, for all their wild, wonderful, authoritative and empathic interventions, in the context of this chapter.

In fact, even the lifestyle gurus get a look in, in the form of an elegant study which examined the effect of simply being told that you are doing something healthy. Eighty-four female room attendants working in various hotels were divided into two groups: one group was told that cleaning hotel rooms is ‘good exercise’ and ‘satisfies the Surgeon General’s recommendations for an active lifestyle’, along with elaborate explanations of how and why; the ‘control’ group did not receive this cheering information, and just carried on cleaning hotel rooms. Four weeks later, the ‘informed’ group perceived themselves to be getting significantly more exercise than before, and showed a significant decrease in weight, body fat, waist-to-hip ratio and body mass index, but amazingly, both groups were still reporting the same amount of activity.*