A news feature in Nature asks whether placebo controls are always a good idea: Why Fake It?
The piece looks at experimental neurosurgical treatments for Parkinson's, such as "Spheramine". This consists of cultured human cells, which are implanted directly into the brain of the sufferer. The idea is that the cells will grow and help produce dopamine, which is deficient in Parkinson's.
Peggy Willocks, a 44 year old teacher, took part in a trial of the surgery in 2000. She says it helped stave off the symptoms for years, but the development of Spheramine was axed in 2008 after a controlled trial found it didn't work any better than a placebo.
The placebo was "sham surgery" i.e. putting the patient through a full surgical procedure, and making holes in their skull, but without doing anything to their brain.
It's cheap and easy to do a placebo controlled trial of a drug - all you need is a sugar pill. But with neurosurgery, it's clearly a lot more involved. A placebo has to be believable. Convincing sham surgery is expensive, time-consuming, and it has real risks, albeit small ones.
Is it ethical to put patients through that?
That, I think, can only be decided on a trial-by-trial basis. It depends on the likely benefits of the treatment, and whether the trial is scientifically sound. Obviously, it'd be wrong to do sham surgery as part of a flawed trial that won't tell us anything useful.
The Nature article, however, goes further than this, and suggests that placebo controlled trials may be unsuitable for testing these kinds of treatments, failing to detect a real benefit in some patients:
There are hints from some of the failed phase II trials that patients followed up beyond study endpoints might tell a more positive story. Some say, therefore, that sham controls are sinking the prospects of valuable drugs.
Anders Björklund, a neuroscientist at Lund University in Sweden who is collaborating with [Roger Barker of Cambridge], says that sham surgery can lead researchers to throw out a strategy prematurely if the trial fails because of technical or methodological glitches rather than a true lack of efficacy.A patient advocate agrees:
I'm not sure about this. If I had Parkinson's, I would certainly hate to miss out on the genuine cure because a trial had failed to recognize that it worked. But equally, I would not be happy to be given a rubbish treatment that would have failed a placebo controlled trial, but never got one, because of arguments like this.
Placebo controlled trials can fail to detect benefits if they are too short, too small, methodologically flawed, or whatever. Certainly, a trial can be placebo controlled, and still crap. But the answer is surely to do better trials, not no trials.
It may well be that we shouldn't rush to do placebo controlled trials until later in the development process, when the technique has been properly refined. But the history of medicine is littered with treatments that "we know work for some people" - that didn't.
Katsnelson, A. (2011). Experimental therapies for Parkinson's disease: Why fake it? Nature, 476 (7359), 142-144 DOI: 10.1038/476142a
According to Perry Cohen, who leads a network of patient activists called the Parkinson Pipeline Project, that’s exactly what is happening. He had always questioned the need for sham surgery, he says, but after the string of phase II failures, “We started saying, ‘Hey, this is a problem. These trials failed, but we know they are working for some people.’”
...Cohen [says] that patients have different priorities and that researchers must take these into account. Researchers use placebo controls to weed out false positives. But for patients, the real ogre is the false negatives — which can sink a therapy before it has been optimized.