Trial limitations, potential sources of bias
stroke
STROKE, SECONDARY
The decision to limit the analysis to the effects of the Restricted vs Non-Restricted elbow range in a secondary analysis was based on our preliminary finding that there was no difference in the effects of training with tDCS. The lack of effect is consistent with more recent results that non-invasive brain stimulation such as tDCS and rTMS only showed main effects on training outcomes when patients were stratified according to the availability of functional reserve in the corticospinal system of the lesioned hemisphereOur results provide data as a proof-of-concept for the use of personalized impairment-based training restricted to the patient’s active elbow control zone. The small sample size may have affected the robustness of our results. Although we had good adherence (88%), some data were lost primarily due to pre-post scheduling (e.g., bringing patients back to hospital centers for the post-treatment testing session) or technical issues (e.g., connectivity during online VR sessions). For example, since the software was meant to be run on an online platform, if there were wifi connectivity problems, we arranged for the VR software to be run as a stand-alone platform on the local computer. Since the VR technology was not accessible in one country (India), the technology was provided by the research project. In addition, the small number of subjects was partly due to the difficulty in recording kinematics in different clinical settings. For example, some data were lost or unusable because of errors in the orientation of recording electrodes. Bias was minimized by blinding personnel responsible for randomization, group allocation, clinical and kinematic evaluation, treatment, and data analysis. Also, all participants were trained while wearing the restrictive elbow brace and arm-sling. The actual reaching range during training for each group was not recorded although the VR program randomly assigned target locations in each task according to the arm workspace calibrated to the individuals’ reaching distance. This was full elbow extension for the Non-restricted group and elbow extension limited by the brace to the elbow flexor TSRT angle in the Restricted group. However, the lack of this information is a limitation of the study.The current study results cannot be generalized to other outcomes, such as health-related quality of life and community participation. Neither can they be generalized to other stroke sub-groups. Finally, results should be interpreted considering that patients were also receiving standard care in the three different countries and, although this was monitored and found to be equivalent between training groups (Table 