randomized trials – The Health Care Blog

What the Story of a Famous Little White Pill Says About How Medical Research Works

Jan 20, 2013• 5

By John H. Schumann, MD

Twenty-five years ago this month, the New England Journal of Medicine published a special report on something that’s become medical gospel:

Aspirin.

That’s right. Not as in “take two and call me in the morning,” but in the realm of the randomized double-blinded placebo-controlled trial. Or what we generally consider the gold standard of evidence in medical research.

If you’ve often heard that bit of jargon but always wondered why it’s so exalted, break it down:

randomized: the assignment of the treatment (aspirin) or placebo (‘inert’ sugar pill) is not given in any planned sequence.
double-blinded: neither the researchers nor the subjects know who is taking what (everything is coded so that analysts can find out at the end).
placebo-controlled: the study compares the treatment against placebo to see if it’s helpful or harmful.

Even though acetylsalicylic acid’s properties as a pain reliever and fever reducer had been known in the time of Hippocrates, it was in 1899 that Bayer first patented and marketed what came to be known as aspirin worldwide.

A mere 89 years later, researchers from the “Physicians Health Study” did something unusual. Citing aspirin’s “extreme beneficial effects on non-fatal and fatal myocardial infarction”–doctor speak for heart attacks–the study’s Data Monitoring Board recommended terminating the aspirin portion of the study early (the study also was looking at the effects of beta-carotene). In other words, the benefit in preventing heart attacks was so clear at 5 years instead of the planned 12 years of study that it was deemed unethical to continue blinding participants or using placebo.

Is Prostate Cancer Screening Truly Harmful?

May 30, 2012• 7

By Peter Ubel

Dr. Timothy Wilt, a member of the United States Preventive Services Task Force, stood in front of the American Urological Association audience and explained why the task force could not recommend that men undergo routine PSA screening. At most, he explained, the test had been shown to benefit one out of 1000 men. Meanwhile, the test would cause hundreds of men to experience anxiety, and scores of them to experience impotence and incontinence from unnecessary treatments.

Twenty minutes later, I stood behind the same podium and asked the audience members to raise their hands if they disagreed with the task force’s conclusion. Ninety percent expressed their skepticism. What happened in the time between Wilt’s presentation and mine reveals a great deal about why experts cannot agree whether screening tests, like the PSA in middle-age men or mammograms in 40-year-old women, bring more benefit than harm, and about what psychological forces impede our ability, as a society, to figure out what basic bundle of healthcare services all insurance companies ought to pay for.

Wilt’s presentation was a model of scientific clarity. He explained that only two randomized clinical trials were conducted with enough scientific rigor to provide useful estimates of whether the PSA test saves lives. One trial showed no benefit and the other revealed the one in 1000 number which the task force took as the best case scenario. Wilt was followed on stage by Ruth Etzioni, a biostatistician at the Fred Hutchinson Cancer Research Center in Seattle. Etzioni presented a statistical model suggesting that the PSA test benefited many more than one in 1000 men.