Development of statistical methodology considering placebo response in randomized controlled trials targeting Alzheimer's disease

Alzheimer's disease (AD) is one of the causes of dementia, which is characterized by long-term decline in cognitive function. Currently, more than 55 million people worldwide are living with dementia, and AD is thought to be involved in 60-70% of cases. As more people live longer, more individuals are developing AD. We urgently need to find effective treatments. Clinical trials are commonly conducted to find effective treatments. These trials compare potential medicine with placebos, which are fake medicines with no real treatment. However, in trials testing potential treatments for AD, most medicine didn't work better than placebos.
One potential reason why these clinical trials have failed is the high placebo response, where groups that took a placebo (placebo groups) showed high improvement in cognitive function, making it hard to detect the true effects of the drugs being tested.
Other disease areas like depression have extensively studied the placebo response. Research in this field suggests that the high placebo response caused many clinical trials for depression drugs to seem unsuccessful, even if the drugs were truly effective. Scientists are developing new statistical methods to account for the placebo response when analyzing the results of these trials. However, research examining the placebo response in clinical trials for AD has been limited. For AD trials as well, understanding the placebo response could greatly contribute to finding better treatments.
In this study, we will use data from past AD clinical trials' placebo groups. Based on previous research, placebo high responders will be defined. Each patient's data will be examined to determine if they are placebo high responders. Using this information, the study will investigate the extent to which placebo response impacts results in clinical trials, and identify characteristics of patients prone to be placebo high responders. It will identify which types of AD patients are prone to be placebo high responders and develop new statistical methods to evaluate treatment efficacy while considering placebo response.
If we can better identify placebo high responders and adjust for their influence, the risk of promising treatments failing in clinical trials due to the participation of placebo responders would decrease. This could make future AD drug trials more successful. Ultimately, this research could help provide effective treatments for Alzheimer's patients worldwide.