A friend of mine pointed me to the above TED talk, by Ben Goldacre. It's a entertaining presentation with lots of interesting content, although Goldacre's discussion of the placebo effect—"one of the most fascinating things in the whole of medicine" (6:32)—is a little weak. At 6:47, he says:
We know for example that two sugar pills a day are a more effective treatment for getting rid of gastric ulcers than one sugar pill a day. Two sugar pills a day beats one pill a day. And that's an outrageous and ridiculous finding, but it's true.Notice that the claim is not about pain, but about actually healing the ulcers.
The source of this claim is apparently a 1999 study by de Craen and co-authors titled "Placebo effect in the treatment of duodenal ulcer" [free full text/pdf]. It's a systematic review based on 79 randomized trials comparing various drugs to placebo, taken either four times a day or twice a day depending on the study. (Note that Goldacre refers to twice a day versus once a day; I'm uncertain of the reason for the difference.) From each trial, the authors extracted the results in the placebo group only, obtaining the following results:
The pooled 4 week healing rate of the 51 trials with a four times a day regimen was 44.2% (805 of 1821 patients) compared with 36.2% (545 of 1504 patients) in the 28 trials with a twice a day regimenThis 8% difference was statistically significant, and remained so even when several different statistical models were used.
However, the authors are up-front about a key limitation of the study: "We realize that the comparison was based on nonrandomized data." Even though the data were obtained from randomized trials, none of the trials individually compared a four-times-a-day placebo regimen to a twice-a-day placebo regimen, so the analysis is a nonrandomized comparison. What if there were important differences between the patients, the study procedures, or the overall medical care provided in the four-times-a-day trials and the two-times-a-day trials? The authors discuss various attempts to adjust for gender, age, smoking, and type of comparator drug, but report that this made little difference. But they acknowledge that:
Although we adjusted for a number of possible confounders, we can not rule out that in this nonrandomized comparison the observed difference was caused by some unrecognized confounding factor or factors.The strength of a randomized comparison is that important differences between groups are unlikely—even when it comes to unrecognized factors. Although the authors go on to consider other possible biases, their bottom line is:
... we speculate that the difference between regimens was induced by the difference in frequency of placebo administration.These results of this study are intriguing, but they're hardly definitive.