A key challenge facing CNS clinical trials is in designing studies to demonstrate efficacy by obtaining a true drug-placebo difference. Readers will learn about how inaccurate ratings, mistakes, bias, protocol violations, and falsified data bring additional challenges. This article uses hypothetical protocol to illustrate how these common challenges put trials at risk. Signant Health\u2019s Dr. Bill Byrom, Dr. Denis Curtin, Dr. David Daniel, Dr. Alan Kott, and Dr. Gary Sachs describe how digital solutions, like eCOA, can help. The team also make predictions on how novel approaches and technology will be used in the future to deliver a better patient experience.