Methodological considerations for transcranial direct current stimulation in clinical trials

Abstract

While recent years have witnessed a steady rise in the number of studies exploring transcranial direct current stimulation (tDCS) as a potential therapy for disorders of the central nervous system, there are to date no FDA approved clinical indications for this form of noninvasive neuromodulation. Successful development of tDCS as an approved therapy in the US and elsewhere will require the implementation of well designed, appropriately powered clinical trials, which, in turn, requires careful consideration of a variety of methodological factors. The choice of study design (e.g. between-subjects, within-subjects) is one the most fundamental decisions in designing a clinical trial. This choice is often influenced by the specific symptoms and natural histories of the disorders being investigated. Disease-related symptoms and disability may influence the design and execution of tDCS trials in other ways, for instance interfering with the ability of patients to participate in studies that involve frequent stimulation sessions in a research setting, or complicating the ability of patients to provide informed consent. Common medical co-morbidities may also influence the efficacy of tDCS as a therapy, either negatively by interfering with the effectiveness of brain stimulation, or positively by providing new treatment targets. The parameters being used to deliver tDCS including stimulation intensity, frequency, and duration, as well as electrode size, number, and location, also play a critical but only partially understood role in tDCS studies. Finally, the use of robust control conditions is an important concern in all clinical trials, including those involving tDCS. This chapter will review these issues as they pertain to the design of tDCS clinical trials, and will conclude with recommendations for the standardization of methods for tDCS clinical trial reporting.