Digitizing Non-Invasive Neuromodulation Trials: Scoping Review, Process Mapping, and Recommendations from a Delphi Panel
Authors: Brunoni Andre R , Ekhtiari Hamed , Antal Andrea , Auvichayapat Paradee , Baeken Chris , Benseñor Isabela M. , Bikson Marom , Boggio Paulo , Borroni Barbara , Brighina Filippo , Brunelin Jerome , Carvalho Sandra , Caumo Wolnei , Ciechanski Patrick , Charvet Leigh , Clark Vincent P. , Kadosh Roi Cohen , Cotelli Maria , Datta Abhishek , Deng Zhi-De , De Raedt Rudi , De Ridder Dirk , Fitzgerald Paul B. , Floel Agnes , Frohlich Flavio , George Mark S. , Ghobadi-Azbari Peyman , Goerigk Stephan , Hamilton Roy H. , Jaberzadeh Shapour J. , Hoy Kate , Kidgell Dawson J. , Zonoozi Arash Khojasteh , Kirton Adam , Laureys Steven , Lavidor Michal , Lee Kiwon , Leite Jorge , Lisanby Sarah H. , Loo Colleen , Martin Donel M. , Miniussi Carlo , Mondino Marine , Monte-Silva Katia , Morales-Quezada Leon , Nitsche Michael A. , Okano Alexandre H. , Oliveira Claudia S. , Onarheim Balder , Pacheco-Barrios Kevin , Padberg Frank , Nakamura-Palacios Ester M , Palm Ulrich , Paulus Walter , Plewnia Christian , Priori Alberto , Rajji Tarek K. , Razza Lais B. , Rehn Erik M. , Ruffini Giulio , Schellhorn Klaus , Zare-Bidoky Mehran , Simis Marcel , Skorupinski Pawel , Suen Paulo , Thibaut Aurore , Valiengo Leandro C. L. , Vanderhasselt Marie-Anne , Vanneste Sven , Venkatasubramanian Ganesan , Violante Ines R. , Wexler Anna , Woods Adam J. , Fregni Felipe 
Published: March 2022

Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. Device appraisal showed moderate digitalization readiness, with high safety and the possibility of trial implementation, but low connectivity. Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; although they reached no consensus about aspects regarding methodological biases. We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.

Graphical Abstract. Consensus Roadmap

(A) Recruitment process. The study procedure started with defining the components of the research problem by the core research team. After defining the problems, two different sets of participants (the steering committee (SC) including key leaders of the field identified by the core team and the expert panel (EP) as a more diverse group of experts identified based on the number of publications based on a systematic review) were identified and were invited to participate in a Delphi study. The study facilitators (first and last authors) led the communications with the SC to design the initial questionnaire through an iterative approach. (B) Evidence synthesis: To collect the available evidence, companies producing portable tES (ptES) devices were contacted, based on the companies suggested by the SC and EP to provide details about the available devices. For mapping methodological processes of digitizing tES trials, two distinct strategies were performed and embedded into the questionnaire, namely SIPOC (Suppliers, Inputs, Process, Outputs, and Customer) and SWOT (Strengths, Weaknesses, Opportunities, and Threats) assessment were performed and embedded into the questionnaire. (C) Consensus development: In the next phase, the questionnaire was validated and finalized via collecting and summarizing opinions. Afterward, the SC and EP responded to the final questionnaire, and results were analyzed providing a list of recommendations for running tES digital trials based on a pre-registered consensus threshold.