Problem With Drug Studies: The Patients?


An acquaintance in graduate school once described to me his father's business and its sad demise.

He claimed that his father, years before, had run a large college preparation service in a small country. My friend's father advertised that he knew how to drastically improve applicants' chances of getting into the elite national university.

Hinting at inside contacts and claiming knowledge of the various forms, deadlines and procedures, he charged an exorbitant fee for his service, which he justified by offering a money-back guarantee to students who were not accepted.

One day, the secret of his business model came to light. All the material that prospective students had sent him over the years was found unopened in a trash dump. Upon investigation it turned out that he had simply been collecting the students' money (or rather their parents' money) and doing nothing for it. The trick was that his fees were so high and his marketing so focused that only the children of affluent parents subscribed to his service, and almost all of them were admitted to the university anyway. He refunded the fees of those few who were not admitted.

He also was sent to prison for his efforts.

Although it's not completely analogous, this story came to mind when I read a recent blog posting in February by Dr. Michael Eades in which he questioned the efficacy of statins in lowering all-cause mortality.

More on this later, but one much less controversial point made by Eades is that miracle drugs, diets and exercise regimens almost always leave at least a tiny room for doubt because they can never be confirmed by randomized, double-blind, placebo-controlled studies.

In such studies, researchers randomly assign people to one of two similar groups, provide the members of one group the drug being tested and the members of the other an identical-seeming placebo. Everything is coded so that neither the researchers nor the subjects know who is receiving what. When the study is completed, the results are analyzed to see if the drug really has any statistically significant effects.

With diet and exercise programs this platinum standard of randomized, double-blind, placebo-controlled studies is clearly impossible because, unless they're zombies, people know whether and how they've been exercising or dieting. With many drug tests, there is the related problem of which subjects adhere to the drug regimen.

A Simple Case

This was part of the problem, for example, with hormone replacement therapy (HRT). For years, it was seen as conferring cardiovascular benefits on the women who took the combination of estrogen and progestin because they suffered somewhat fewer heart attacks, strokes and the like.

There was, it's now clear, a biasing variable in these earlier studies: The women involved were, for the most part, relatively affluent and health-conscious, and their lower rate of cardiovascular problems was probably due to this and not to their taking HRT.

In fact, a large subsequent study on HRT published in the Journal of the American Medical Association overturned the conventional wisdom about the treatment. Eliminating the self-selection bias, it found that the relative risks of heart attack, stroke and breast cancer were 1.29, 1.41, and 1.24, respectively, suggesting that women taking HRT incur, respectively, 1.29, 1.41 and 1.24 times the risk of women not taking it.

A More Interesting Twist

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