title: Challenges in Recruitment for the Study of Noninvasive Brain Stimulation in Stroke: Lessons from Deep Brain Stimulation.
abstract: OBJECTIVE
  Noninvasive brain stimulation (NIBS) can augment functional recovery following stroke; however, the technique lacks regulatory approval. Low enrollment in NIBS clinical trials is a key roadblock. Here, we pursued evidence to support the prevailing opinion that enrollment in trials of NIBS is even lower than enrollment in trials of invasive, deep brain stimulation (DBS).
  
  
  METHODS
  We compared 2 clinical trials in stroke conducted within a single urban hospital system, one employing NIBS and the other using DBS, (1) to identify specific criteria that generate low enrollment rates for NIBS and (2) to devise strategies to increase recruitment with guidance from DBS.
  
  
  RESULTS
  Notably, we found that enrollment in the NIBS case study was 5 times lower (2.8%) than the DBS trial (14.5%) (χ(2) = 20.815, P < .0001). Although the number of candidates who met the inclusion criteria was not different (χ(2) = .04, P < .841), exclusion rates differed significantly between the 2 studies (χ(2) = 21.354, P < .0001). Beyond lack of interest, higher exclusion rates in the NIBS study were largely due to exclusion criteria that were not present in the DBS study, including restrictions for recurrent strokes, seizures, and medications.
  
  
  CONCLUSIONS
  Based on our findings, we conclude and suggest that by (1) establishing criteria specific to each NIBS modality, (2) adjusting exclusion criteria based on guidance from DBS, and (3) including patients with common contraindications based on a probability of risk, we may increase enrollment and hence significantly impact the feasibility and generalizability of NIBS paradigms, particularly in stroke.
authors: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors: Kelsey A
authors: KA
authors: Potter-Baker
authors: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors: Corin E
authors: CE
authors: Bonnett
authors: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors: Patrick
authors: P
authors: Chabra
authors: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors: Sarah
authors: S
authors: Roelle
authors: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors: Nicole
authors: N
authors: Varnerin
authors: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors: David A
authors: DA
authors: Cunningham
authors: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
authors: Vishwanath
authors: V
authors: Sankarasubramanian
authors: Department of Neurology, Case Western Reserve University, Cleveland, Ohio; Department of Neurology, Louis Stokes Department of Veterans Affairs Medical Center, Cleveland, Ohio.
authors: Svetlana
authors: S
authors: Pundik
authors: Neurology Clinical Division, Neurology Department, Hospital das Clinicas, São Paulo University, São Paulo, Brazil; Hospital Israelita Albert Einstein, Department of Neurology, São Paulo, Brazil.
authors: Adriana B
authors: AB
authors: Conforto
authors: Center for Neurological Restoration, Neurosurgery, Neurological Institute, Cleveland Clinic Foundation, Cleveland Clinic, Cleveland, Ohio.
authors: Andre G
authors: AG
authors: Machado
authors: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Physical Medicine and Rehabilitation, Neurological Institute, Cleveland Clinic Foundation, Cleveland, Ohio. Electronic address: plowe2@ccf.org.
authors: Ela B
authors: EB
authors: Plow
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000502:physiology*; D002986:Clinical Trials as Topic; D046690:Deep Brain Stimulation / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology; D059408:Pain Management; D020127:Recovery of Function / Q000502:physiology*; D020521:Stroke / Q000150:complications / Q000628:therapy*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
keywords: DBS; TMS; clinical trial; patient recruitment; rehabilitation; tDCS