The Power of Randomized Trials

March 09, 2009

I'm not a doctor, and I don't play one on this blog, but my wife is and she pointed me to a story that should give pause to anyone questioning the value of randomized control trials (RCTs)---and provide a tonic to my invitation to criticize RCTs.For most of the 1990s, American doctors advised postmenopausal women to take artificial hormones to replace the natural ones dwindling in their bloodstreams. By the end of the decade, half of such women were on the drugs (source). Evidence from "cohort" studies, notably from the long-standing Nurses' Health Study group of 200,000+ nurses, showed that women who took artificial estrogen and progestin experienced less heart disease.Then the U.S. National Institutes of Health funded the Women's Health Initiative (WHI), which performed randomized trials of, among things, hormone replacement drugs, giving some women the drugs and others (unbeknownst to them) fake "placebo" pills. So harmful did the hormones prove that the trial was halted early and the conclusions published: women taking replacement hormones had more heart disease, as well as more strokes and more invasive breast cancer. (Death rates within the study period, however, were not higher.)The contradictory results from the older cohort studies apparently mystified the experts. Perhaps nurses who responsibly reduced their risk of heart disease by eating well and not smoking were also more apt to follow the latest medical thinking by starting hormone replacement therapy, thus making it look like the drugs reduced heart disease. Notably, most careful non-randomized microfinance studies follow cohorts (e.g., e.g., e.g.)After the randomized trial results were published, drug company promotion and physician prescription of hormone pills plunged. The national breast cancer rate fell too:breast cancer incidence 1975-2005.jpgNot convinced? Good. We can't be certain that the WHI caused the drop by announcing the results of its randomized trial. However, a new study tracks how fast heart disease, strokes, and cancer declined in those WHI subjects who were taken off hormones after that study was halted. Extrapolating, it estimates that hormone replacement therapy caused 200,000 extra breast cancer cases between 1992 and 2002 in the United States. (It also finds that another theory, declining rates of mammogram use, cannot explain the drops in the number of breast cancer cases reported.)Data on breast cancer incidence from the National Cancer Institute:breast cancer incidence 1975-2005 table.jpg


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