Dr Ron Eccles Discusses the Placebo Effect in Chronic Cough Clinical Trials

The placebo effect is a major problem in cough trials and can make it impossible to tell the true pharmacological effect of the medicine being studied, said Ron Eccles, BSc, PhD, DSc, emeritus professor at Cardiff University.

Transcript

How big of a problem is the placebo effect in clinical trials for cough therapies?

Yeah, well, how big a problem is the placebo effect? I would say that the placebo effect is present with every medicine that you take. Now, it's a particular problem with cough clinical trials, because cough is under voluntary control. I can cough now. That cough is indistinguishable from any sort of cough you would record in a clinical trial.

Cough can be voluntarily inhibited, as well. We showed this quite nicely in experiments where we had traffic lights in front of people. They were suffering from acute cough associated with common cold. We also showed it with capsaicin-induced cough, which is a pepper-like substance. And we showed people can completely suppress the coughs associated with common cold and with capsaicin-induced cough, showing the voluntary control.

Well, that voluntary control actually links in with the placebo effect. If people know that they are being given an active treatment, then they have a sense of belief and expectation about that treatment, and they can control the way they cough. In the same way, you will control the way you cough if you are in the theater and it's coming up to a very important part of the scene. Everybody is quiet. But after that scene is over, you listen; a lot of people start coughing. They've suppressed cough during that important scene.

So, placebo effect is very big in cough, and it is a major problem in cough clinical trials. Because the placebo effect can sometimes be as large or just as big as the medicinal effect or pharmacological effect that you're trying to measure, and dwarf it or swamp it.

How do you get around the issue of the large placebo effect in cough clinical trials?

Well the first thing is, the clinical trial should be blinded. Now, if you read the description of clinical trials, they always say, "This clinical trial was conducted with a matched placebo." Now, a matched placebo means the same in color, taste, smell, so that the participants in the clinical trial cannot tell the difference.

However, it's difficult to control for side effects of a medicine. The side effects can unmask and unblind the medicine. And really, if you're considering a clinical trial, what you should do is make sure, first of all, that the blinding of the clinical trial is adequate. Otherwise, the trial is just like an open trial, when the participants can know quite easily what they're being tested with, and this will unbalance the trial. It will unbalance it, so the placebo effects will be different on the 2 sides of the trial, making it impossible to determine the pharmacological efficacy of a medicine.

Well, how could you test for blinding? Very easily. You get healthy subjects, you give them the medicine and you give them the matched placebo in a double-blind way. And then you ask those subjects, “Which treatment were you allocated?” If the trial is blinded properly with a properly matched placebo, the chances of them detecting which medicine they’re on should be no different from chance itself: 50/50.

However, if people can tell which medicine they're on, then it's really not worth proceeding with a clinical trial. The trial is unblinded and it becomes impossible to determine the true pharmacological effect of a medicine.