When randomized, controlled clinical trials are designed with a high likelihood of being positive in favor of the sponsor's drug, they are flawed by design bias. This type of bias is not consistent with the concept of equipoise (ie, the uncertainty principle) that is a central ethical principle of clinical research. The uncertainty principle is supposed to ensure that a subject may be enrolled in a phase 3 randomized, controlled clinical trial only if there is a true uncertainty about which trial arm is most likely to benefit the patient. Focused, scholarly surveys20,25–33 of approximately 1,000 randomized, controlled clinical trials published from 1990 to 2005 showed that systematic bias has favored products made by the company funding the research. Studies32 funded by drug companies were more likely to have outcomes favoring the sponsor than were other studies (odds ratio, 4.05; 95% confidence interval, 2.98 to 5.51). An analysis32,34 of many of these studies suggested that there likely was an intent to “stack the deck” in favor of the sponsor's product because there was an inappropriate use of a comparator drug (eg, used in a dose that was unlikely to be effective). Similar surveys20 of studies published from 1999 to 2001 revealed similar proindustry trends and included surgical as well as medical trials. In a study35 that sought to determine the frequency with which equipoise conditions were met in industry-sponsored randomized, controlled trials in rheumatology, the authors studied abstracts accepted for the 2001 American College of Rheumatology meeting; in every trial (45 of 45 trials), results were favorable to the sponsor, indicating that the results of the trials could have been predicted in advance solely by knowledge of sponsorship (p < 0.0001).