How should we design future mechanistic and/or efficacy clinical trials?
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology – January 01, 2024
Source: PubMed
Summary
Improvements in neuropsychiatric clinical trials could enhance therapeutic signal detection, addressing issues like high placebo response rates and imprecise assessments. With a focus on new molecular targets and innovative treatments like psychedelics, the review highlights the need for better methodologies. For instance, adopting sequential parallel comparison designs and confirming subject enrollment appropriateness can refine trial efficiency. By implementing these strategies, researchers aim to boost the performance of trials, ultimately leading to more effective treatments for neuropsychiatric conditions.
Abstract
The emergence of new molecular targets, together with the development of new approaches to neuropsychiatric diseases, involving psychedelics as well as gene and cell therapies, are creating the need to improve the efficiency of mechanistic and/or efficacy clinical trials. This review article will discuss a number of issues that have hampered our ability to detect therapeutic signals, from excessive placebo/sham response rates to the imprecision of diagnostic and outcome assessments. In addition to reviewing the limitations of current efficacy and mechanistic neuropsychiatric clinical trials, this review presents some of the methodological approaches that may improve the overall performance of our neuropsychiatric trials, including the adoption of novel study designs such as the sequential parallel comparison design and independent confirmation of the appropriateness of subjects' enrollment. In addition, this review will discuss several designs that make mechanistic clinical trials more precise.