More intriguing is the case of the pre-statin heart drug clofibrate, which Eades cites. As the New England Journal of Medicine reported almost 30 years ago, the five-year mortality rate among the 1,100 or so men treated with this drug was 20.0 percent, whereas the rate for the nearly 2,800 men given the placebo was 20.9 percent. Nothing mysterious there. The drug was useless.
But, and here's the odd part, those men who filled 80 percent or more of their prescriptions over the time interval had a 15.0 percent five-year mortality rate whereas those who filled their prescriptions less than 80 percent of the time suffered a 24.6 percent mortality rate.
Even more odd is that similar percentages resulted for those who were diligent about taking the placebo. There was a 15.1 percent mortality rate for them and a 28.3 percent mortality rate for those who took the placebo less than 80 percent of the time. Something a bit more than confirmation bias, confounding variables and a simple placebo effect was going on.
A more recent 2005 article in Lancet showed the same anomalous finding of comparable percentages when the heart drug candesartan was pitted against a placebo in a randomized study. More generally, a 2006 meta-analysis of the effect of adherence on medical outcomes in the British Medical Journal found the same thing.
Those who adhered to what was offered them, whether to the drug or to the placebo, were somehow different from those who did not and they fared significantly better.
Given this phenomenon, it makes sense to ask how one can evaluate the effectiveness of drugs in cases where adherence may mask the uselessness of expensive drugs?
Eades, who advocates a low-carbohydrate/high protein diet in his several books on nutrition, has written extensively about adherence and related matters on his popular medical Web site -- specifically, as mentioned, regarding the anti-cholesterol statin drugs. (Eades' statins article: http://www.proteinpower.com/drmike/statins/more-statin-madness/#more-2656)
He suggests that further analysis of a large study reported in the February 2009 issue of Archives of Internal Medicine might reveal that the seemingly positive effects of statins announced there may be merely a consequence of the adherence effect. That is, he claims that, like clofibrate, candesartan and other drugs, statins may not do much of anything for all-cause mortality.
A few other researchers agree with his intriguingly iconoclastic claim, but it's important to note that the it is very much at odds with the present medical consensus on statins. (The matter, however, is extremely complicated, the patient groups very diverse, and the relevant studies of quite disparate types.)
Nevertheless, I emphasize that one needn't agree with the claim to realize that the adherence effect is quite general. The point is methodological, not medical. Moreover, instances of it might help explain the efficacy of belief and adherence in many realms other than medicine, drug testing, and college admissions.
A notable example is religion, where other enhancers of the placebo effect, such as a recognized "brand" and dispensation by an authority figure, also play a role.