For unknown reasons, placebos reduce @entity410 in clinical trials in many @entity1 . It is also unclear why some drugs showing statistical superiority to placebo in one trial may fail to do so in another. Using Seizuretracker.com, a @entity1 -centered database of 684,825 @entity410 , we simulated "placebo" and "drug" trials. These simulations were employed to clarify the sources of placebo effects in @entity302 , and to identify methods of diminishing placebo effects. Simulation 1 included 9 trials with a 6-week baseline and 6-week test period, starting at time 0, 3, 6   24 months. Here, "placebo" reduced @entity410 regardless of study start time. Regression-to-the-mean persisted only for 3 to 6 months. Simulation 2 comprised a 6-week baseline and then 2 years of follow-up. @entity410 frequencies continued to improve throughout follow-up. Although the group improved, individuals switched from improvement to worsening and back. Simulation 3 involved a placebo-controlled "drug" trial, to explore methods of placebo response reduction. An efficacious "drug" failed to demonstrate a significant effect compared with "placebo" (p   =   0.12), although modifications either in study start time (p   =   0.025) or baseline population reduction (p   =   0.0028) allowed the drug to achieve a statistically significant effect compared with placebo. In @entity302 clinical trials, some @entity410 reduction traditionally attributed to placebo effect may reflect the natural course of the disease itself. Understanding these dynamics will allow future investigations into optimal clinical trial design and may lead to identification of more effective therapies. Ann Neurol 2015;78:329-336.

Confusing placebo effect with natural history in XXXX : A big data approach.

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity410 :: ('MESH:D012640', 'Disease') :: ['seizure', 'seizures', 'Seizure'] @entity302 :: ('MESH:D004827', 'Disease') :: ['epilepsy']
@entity302 :: (MESH:D004827,Disease) :: ['epilepsy']
