Remote Delivery Will Expand tDCS Clinical Study

Neurophysiologic and clinical trials with tDCS increasingly reinforce that efficacy increases with multiple sessions (Mori et al., 2010, 2013; Acler et al., 2013; Ferrucci et al., 2014; Meesen et al., 2014; Tecchio et al., 2014), with effects thought to be cumulative. Many clinical investigators apply tDCS in conjunction with a behaviorally-based treatment approach to improve outcome (Demirtas-Tatlidede et al., 2013; Martin et al., 2013b; Brunoni and Vanderhasselt, 2014; Brunoni et al., 2014; Flöel, 2014), which must be repeated alongside tDCS. The clinical utility of tDCS must be established through trials that are sufficiently-powered, with adequate dose (Peterchev et al., 2012) and session number, and with precise protocol control. However, multiple sessions require subjects to repeatedly travel to the clinic for each treatment, placing significant and often insurmountable burden to patients and their caregivers, at the same time associated with significant provider time and cost, especially as the sample size increases (Brunoni et al., 2012a; Holland and Crinion, 2012; Ferrucci et al., 2014; Meesen et al., 2014; Shiozawa et al., 2014; Vaseghi et al., 2014). For example, in a sample of 64 subjects treated for depression, Loo et al. administered 30 sessions across 6 weeks (Loo et al., 2012), followed by up to 20 maintenance treatment sessions spaced over 6 months (Martin et al., 2013a). Similarly, during the 6 month follow up of a depression trial, Valiengo and colleagues showed a dropout rate of 17 of 42 subjects—with almost all dropouts citing the burden of regular visits to the clinic (Valiengo et al., 2013).

A remedy to this feasibility problem is controlled remote tDCS application, with a common protocol that ensures safe, well-tolerated and reproducible remotely-supervised tDCS. Combining this remote approach with behaviorally-based treatments (e.g., cognitive or physical rehabilitation exercises completed at home, or behavioral therapy delivered through remote, web-based platforms) will allow investigators to reach subjects either through satellite clinic locations or directly from their home or care facility.

While there has not yet been a clinical trial involving remotely-supervised tDCS, the home use of tDCS over a 3 year period has been reported as both safe and effective in the case of a patient with schizophrenia through 20 minute daily sessions administered by a medically licensed caregiver (Andrade, 2013).We propose here a protocol for remotely-supervised delivery of tDCS for clinical trials, with the expectation of maintaining the same level of uniformity and compliance that would be seen with tDCS sessions administered in the clinic. This step represents an extension of currently-accepted tDCS methodology to allow for trials to include more subjects and to remove any logistical limits on the number of sessions studied.

The approach proposed for remotely-supervised tDCS can be applied to double-blind trials. tDCS clinical trial devices have been developed which deliver active or sham stimulation depending on the individual subject code keyed in, leaving both device operator and subject blinded to treatment assignment. There is no reason why blinding should be any less available when the subject (or proxy) operates the device under remote supervision.

Training of the tDCS Research Staff

Study research staff will first be trained in tDCS treatment technique and in administering tDCS to others. Staff will be trained using standard-operating-procedures (SOP) specifying all subject interactions as well as device usage. In terms of subject interaction, study research staff will be trained to monitor for study-specific “stop” criteria following a decision-tree-based flowchart that allows for evaluation of eligibility to continue at each progressive step. At baseline visits (in clinic) tDCS research staff will complete a checklist to screen subjects for at home tDCS (see Figure ​Figure11 for an example).

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Figure 1

Example of subject checklist.

Following training on screening procedures, study research staff will be briefed on the usage of the device and the location of headset placement. In addition, selected research staff will be trained with and have access to a guide that details (e.g., the device manual), in a step-by-step fashion, the procedures that are required to configure and program devices prior to release to subjects, for example programming device unlock codes for one-time use to be provided prior to each session. Prior to releasing a device to a subject, selected research staff must program the intensity, duration, and condition (active or sham) of each planned session, along with code that limits the number and frequency of sessions. In the case of code-based session release, research staff will be instructed to withhold any one-time use codes until subject device placement and setup are deemed appropriate.

Research staff will be trained in the preparation and testing of any devices and accessories (e.g., kits) release to subjects, as documentation of material release. Through the duration of the study, technicians will be trained to monitor subjects for any unexpected adverse events (e.g., atypical discomfort) or misuse of the device. At the end of the study, technicians will be instructed on how to evaluate retrieved physical device materials (e.g., headgear/stimulator condition, expendables) and download any data stored on the device (e.g., completion codes for each subject’s study sessions, stimulation history of each code issued) as relevant to confirm compliance (Figure ​(Figure22).

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Figure 2

Guidelines for training.

In addition to training specific to the implementation of remotely-supervised tDCS as describe above, the clinical research team needs to be skilled in other aspects of clinical trial methodology, including screening of subjects, monitoring of subject progress and evaluation of outcomes.

Initial and Ongoing Assessment of the User’s Capability to Participate in tDCS Remotely

A precisely defined protocol (decision-tree-based flowchart) will be closely followed through the duration of the study for each subject. Study “stop” criteria (Figure ​(Figure3)3) will be reviewed at each stage of the trial: screening, baseline, study sessions, and follow-up. If stop criteria are met at any time throughout the study, the session and/or trial participation will be terminated as specified in the protocol. Following an initial screening, at least one baseline visit will confirm the subject’s tDCS aptitude and tolerability. Before any subject is sent home with a device, it will be determined whether the subject-or designated proxy- can properly follow the steps to ensure correct electrode preparation and placement, low impedance and safe removal of the device, and whether the subject can tolerate the stimulation period.

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Figure 3

Example of study flowchart with stop criteria.

Throughout the study, general compliance will be maintained through stop criteria that exclude subjects who continually fail to set up a device properly or fail to attend regularly scheduled sessions. In addition, if any subject reports an unexpected level of discomfort, pain, or desire to withdraw, the session and/or ongoing study participation may be terminated. At the end of the study, the record of completed and uncompleted sessions, recorded by the device itself, will be reviewed for all subjects who successfully met study criteria. This will be used to determine both individual subject and overall trial compliance based on pre-determined criteria.

Supportive Training Procedures and Materials (Including Assessments of the User and/or Caregiver)

The protocol will be supported by a manual of operating procedures for study staff. For designs with remote supervision of self- or proxy-administered tDCS, that there be at least two in-person training sessions with study staff, including training and practice for the real-time remote supervision procedures (e.g., a training session with a study staff member that includes connection to another remotely-located study staff member via secure internet-based video conference).

For subjects who meet criteria for study continuation, subsequent sessions will be completed with the remote technician alone, with the nature and length of ongoing monitoring to be specific to the subject or trial. For instance, some subjects may require remote monitoring indefinitely, while other trials may use remote monitoring for a training period only.

The protocol will include sequential safety, tolerability and compliance “stops” administered by the supervising study staff throughout the course of the treatment sessions to ensure appropriate use. For instance, potential concerns include failure to place the headset and electrodes correctly, selecting incorrect electrode polarity, inadequate electrode saturation, lack of compliance, and loss of precision in electrode placement.

Each subject will be provided with supportive and readily-accessible training materials (Figure ​(Figure2).2). These should include an instruction manual (potentially supported with an instructional video) and a method to self-report (electronic or binder). These materials are designed as a resource to the subject to reference or confirm study details. In addition, they serve the purpose of remotely training subjects or caregivers who look to clarify items of set-up or device usage. The self-report binder will provide the subject with forms that measure adverse events, assess tolerance, along with study-specific measures (e.g., mood). While the manual and video (if used) will serve as ongoing training procedures, the self-report forms will enable the subject and caregiver to assess the experience throughout the study. Any remotely-delivered adjunctive behavioral therapy (e.g., cognitive or physical training) will be trial-specific with a supplemental protocol and procedures.

Simple and Fail-Safe Electrode Preparation and Positioning

The essential aspects of reproducible tDCS dose (defined in Peterchev et al., 2012) are electrode preparation and montage (addressed in this section) and waveform (addressed in the next). Remotely-supervised tDCS administration would reduce barriers to reliably apply tDCS away from the treatment center.

The headgear should be designed to allow simple and consistent placement of electrode at desired locations on the scalp (Figures ​(Figures4,4, ​,5)—for5)—for example headband snaps for the sponges to be placed on the headband to ensure consistent correct placement.

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Figure 4

Example of hardware-based waveform control. Users are provided with an individual device and accessories such as the 5x-Session Home Kit (A)The subject checks in with the supervisor before and after each session (B). The supervisor unlocks operation before each session by providing a code (B). The subject enters only the code provided with no access to device programming or stimulation settings. The subject uses custom fit headgear to position electrodes (C,D). The device automatically collects compliance data and may also prompt the user for information (E). Details of implementation will be customized to each clinical trial while maintaining the principles of supervised neuromodulation (F, G). (Image courtesy of Soterix Medical Inc.)

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Figure 5

Example of software-based waveform control. Users are provided with an individual stimulator, a discharge key, and accessories such as the 5x-Session Home Kit. The supervisor limits stimulation by programming the discharge key. The subject plugs the discharge key into the device and presses a single button to activate stimulation. The subject uses custom fit headgear to position electrodes. The device automatically collects compliance data which is stored in the discharge key. Details of device implementation will be customized to each clinical trial while maintaining the principles of supervised neuromodulation. (Image courtesy of Soterix Medical Inc.)

Subjects will be screened for aptitude with the specific headgear as part of inclusion/enrollment. Participation is contingent on the ability to properly apply the headset and correctly operate the device. The headgear may be marked in a way that facilitates reliable setup, for example the headset will be labeled “RED” and “BLACK” to confirm that color coded cables are properly placed, ensuring anode (RED) and cathode (BLACK) placement (white can be substituted for red if color blindness is a concern). The headset should be designed to fit reliably on the head, for example designed with a market to align with the bridge of the nose at midline. Headsets may come in multiple sizes and/or allow adjustment by research staff. The device includes an impedance meter and will not allow access until headgear and electrodes are accurately and correctly placed.

The headset should be designed to minimize error in electrode placement, ideally allowing just the montage designed for the specific trial (Figure ​(Figure6),6), e.g., bifrontal montage (for dorsolateral prefrontal cortex target application) or M1-SO montage (for motor cortex target applications).

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Figure 6

Guidelines for study equipment.

Subjects/proxies should be provided with kits which include all of the necessary supplies for the entire study or until expendable can be replenished (by either a visit to the clinic or visit by study personnel to the subjects’ home or care-facility). Components should be labeled properly in order to simplify application, minimize confusion, and prevent error (e.g., mark each pair of sponges by session number). The subject manual should clearly explain the contents of the kit and the correct use of each component.

Also of note, re-use of sponges across subjects is not hygienic. Re-use of the sponge across sessions, even when cleaned, is not recommended for supervised home use- single-use sponges increase tolerability, cleanliness, and reproducibility. Medical grade sponges are required to comply with biocompatibility requirements, and labeling for re-use would require testing under the intended conditions of use—which are complex and variable in the case of home-application. Reliable control of cleanliness, much less contamination, would prove difficult in home use (would not for example be reliably detected by impedance check or remote observation).In addition, attempt to remediate these sponge re-use concerns would increase the operator and patient burden for monitoring and preparation (e.g., concerns about storage, residue from skin/hair product).

Strict Dose Control for Each Session

Control of stimulation parameters is the second essential aspect after electrode placement. For tDCS essential parameters are the intensity, duration (along with any ramp), and condition (active or sham) of stimulation. For multiple sessions, the number and interval of sessions is critical. For remotely-supervised tDCS, limitations on the number and timing of sessions, along with control of each session intensity and duration is pivotal (Figure ​(Figure6).6). Providing subjects with clinical stimulators that do not limit either is not safe or supportive of reproducible protocols.

Two general approaches to control stimulation parameters under remotely supervised-tDCS can be considered. In the first case, “hardware” based limitation (Figure ​(Figure4)4) provides subjects with equipment that is pre-programmed to provide a limited number of sessions with limited interval. For example, the stimulator will provide only 10 sessions, with pre-set intensity, duration, and condition, with a maximum of one session every 23 h. Once 10 sessions have exhausted, the device no longer provides output until the entire hardware or a component (storage disk) is replaced. With “hardware” limitations, it is not necessarily possible to remotely stop use before the 10 sessions are activated. The Soterix Medical/Neuroconn Mobile transcranial Direct Current Stimulator (Mobile) and Magstim/Neuronica HDC-Kit are example of “hardware” based limitation. Subjects or caregivers are required to return to the clinic to replenish expended hardware—supervisors may be provide a “pack” containing multiple dose-control hardware units (e.g., 10 storage disks with 10 sessions each for 100 sessions) but this effectively extends the window where control of dose is limited.

In the second case, “software” based limitation (Figure ​(Figure5)5) subjects are provided with a device which is deactivated until a code is provided by the research staff. The code typically unlocks a single session which a pre-set duration and intensity. After a single discharge, the device is inert until a new code is provided. This allows the remote supervisor to tightly control compliance, for example not providing a code until proper electrode set-up is confirmed by video, provides an opportunity for supervisor to directly interact with subject and gather feedback and data for each trial. In this situation, the remote supervisor may vary the provided code based on subject experience. Soterix Medical transcranial Direct Current Stimulator mini-Clinical Trials system (Mini-CT) is one example of “software” based limitation. Given stimulators can be programmed with excess of codes (e.g., thousands), there is no need for subjects to return to the clinic to replenish hardware.

In both “hardware” and “software” based governing for remote supervision, the subject or caregiver does not program session intensity of duration which enhances safety and reproducibility. In case of blinded treatment, the subject may not know which device/code is real or sham treatment. Double blinding may also be implemented by blinding the remote supervisor.

The user manual should clearly explain the hardware contents of the kit and the correct set-up of the device, such as entering a code or reading the display.

Ongoing Monitoring for Compliance

While in-person monitoring will be completed during the initial sessions, subjects may be monitored and/or contacted to confirm compliance throughout the remaining sessions. Subject interaction will be maintained (e.g., through secure video) to quantify compliance (device preparation, electrode saturation/placement, stimulation protocol) with corresponding corrective steps. As an example, secure video will be scheduled and maintained with each subject daily. Visual confirmation will ensure proper set up, appropriate home environment, and acceptable impedance. Following these checks during monitoring, subjects will be given their one time use code for that session (Figure ​(Figure77).

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Figure 7

Guidelines for ongoing assessment.

Ongoing Monitoring for Treatment-Emergent Adverse Effects

Before starting a session, study staff will ask the subject about any adverse events since the last session, with clearly defined stop criteria if anything is reported that is of clinical concern related to safety or tolerability. In addition, subjects will be asked to report pain and/or discomfort level at set points during the stimulation. If pain crosses a given threshold, there will be an immediate stop in place in order to prevent any risk of skin burn (Loo et al., 2011) and the supervising staff will assess whether this has occurred due to suboptimal treatment technique. If tDCS causes pain above the given threshold despite adequate treatment technique, subjects will be withdrawn from the study. After the session, subjects will be again assessed by study staff for any adverse events. Subjects will also record their experience in the study-specific materials.

Attention Deficit Hyperactivity Disorder (ADHD)

The immediate facilitatory effects of tDCS on cognitive abilities often seen impaired in ADHD has prompted interest in whether or not the technique might have a therapeutic effect. For instance, a recent study of ADHD-diagnosed children in another experiment showed that 0.75 Hz oscillating tDCS increased EEG-recorded slow wave oscillation during sleep, and subsequent memory recall the next day (Prehn-Kristensen et al., 2014). One brief tDCS trial in non-ADHD subjects showed better response inhibition task performance after 5 consecutive days of training with concurrent 1.5 mA anodal tDCS stimulation than training alone (Ditye et al., 2012). The latter suggests that tDCS paired with cognitive training/rehabilitation techniques might have the highest potential for efficacy in minimizing ADHD-related behavioral dysfunction. However, previous trials that combine these therapeutic approaches typically last 1–3 weeks, making clinic visits impractical for a typical family that contends with school demands and extra-curricular activities, worsened when there is more than one school-aged child in the home. Any clinic-based tDCS trial for ADHD not only would be plagued by poor compliance and high dropout, but it is also likely that only the most motivated of families and subjects would complete treatment, complicating generalizability and efficacy inferences.

Remotely-supervised tDCS performed is an obvious approach to circumvent the main obstacles, but the age and behavioral characteristics of the patient population introduce unique issues to any home-based tDCS clinical trial. ADHD is a behavioral disorder whose hallmarks are distractibility, restlessness, and motivational issues–all of which must be managed effectively within a standardized tDCS delivery protocol. Although self-administered tDCS for adults diagnosed with ADHD certainly is feasible, it is more likely that trials will consider tDCS with older children or adolescents, as tDCS has been shown to be safe with these age groups. However, most institutional review boards will not likely approve trial protocols where youth are asked to set up and administer tDCS themselves, suggesting effective trials must plan to overcome and troubleshoot issues arising from parent training to administer tDCS properly. Such issues include effective parent screening/training, attention to how dyadic interactions influence motivation, and special care in assessing compliance and outcome. To accommodate these special considerations, we recommend a trial design that at minimum includes: (1) a clinic visit for consent, clinical assessment, and training with particular attention paid to educating families that treatment must be a “whole family” cooperative effort, (2) an “at home” visit prior to treatment so that research staff can assess and advise tDCS equipment set up and other technical issues, (3) careful consideration of whether every tDCS session should be remotely-supervised (e.g., via video teleconferencing) to ensure optimal protocol adherence; and (4) formal consideration in trial design of how ADHD-related behavior interacts with both treatment delivery, motivation, or outcome.

Some specific recommendations for ADHD protocols include:

• - Parent preparedness, training, and motivational issues: Informed consent for a remotely-supervised tDCS trial should emphasize the multiple types of training required for parents who will administer tDCS. At minimum, parental tDCS technical proficiency should be demonstrated as suggested above, with at least 1 clinic visit and 1 remotely-supervised session, if not at each daily session. If computer-administered cognitive training techniques will accompany tDCS stimulation, separate training should be provided in how to start, stop, and evaluate the successful implementation of such techniques. In addition, parent training should be provided in how to properly motivate their ADHD-diagnosed child. Obviously, an important goal is to avoid punitiveness or coercion that might occur if parents are more motivated than their children, but it is equally as important is to standardize and measure motivation across the trial. For example, simple behavioral contingency management techniques should be considered as standard, especially for younger age groups. Protocol-specific guidelines on how and when to provide positive reinforcements should be made explicit; their use should be quantified by trial staff weekly.

• - Dyadic interaction impact: It is not yet known what interaction styles or personality factors might make some parents more effective in operating and supervising tDCS at home than others. Until such study has been done, we recommend that each trial should make effort to formally assess the nature of parent-child dyadic interactions or familial relationships styles to see if they moderate treatment compliance or outcome.

• - Preparation for tDCS delivery and Monitoring of Potential Treatment Barriers: Homes with children are different than those without. For tDCS with a child or teenager, tDCS should be set up in a specially-designated quiet room and performed without distraction or interruption, preferably with the cooperation of the whole family during treatment delivery to reduce distractions. Protocols should set clear guidelines for whether or not breaks are permitted during training and set guidelines for them. A standardized compliance checklist should be used for each session, which emphasizes whether ADHD-related behaviors that could have interfered with treatment occurred and how they were managed. Any concurrently-done computer-administered cognitive training ideally will be internet-enabled. This will allow research staff to remotely verify that any exercises were set up and run correctly, as well as offers the potential for any behavioral performance data to be uploaded for secure storage at the clinic site after each treatment session.

• - Careful Choice of Outcome Measures: Although it is likely that the primary outcome measures of any tDCS trial would be performance on tests of a specific cognitive domain, (either because it is specifically targeted by concurrent cognitive training or merely because it is one of several domains often impaired in ADHD), secondary outcome measures should include ADHD symptom severity checklists or ADHD “problem behavior” inventories (e.g., Brown ADD Scales). Because of the subjective nature of the latter types of assessments, it is important to use multiple respondents (e.g., parent and teacher). Similarly, the most effective trials will include appropriate placebo conditions in order to mitigate expectancy effects.

Depression

There is a long history of the use of “brain polarization”, essentially an earlier form of tDCS often given at lower stimulus intensities, to treat depression (Arul-Anandam and Loo, 2009). Over the last decade, in the context of the emergence of brain stimulation treatments for depression (e.g., transcranial magnetic stimulation) and developments in tDCS equipment, methodology and scientific understanding, interest has rapidly emerged in tDCS as a treatment for depression. tDCS has been applied both to treatment resistant depression (i.e., in subjects who have failed to improve after treatment with antidepressant medication) and to non pharmacotherapy resistant depression, as some patients may prefer a non medication form of treatment. From 2006, evidence from several placebo-controlled, randomized clinical trials has indicated significant antidepressant effects for tDCS (Loo et al., 2012; Brunoni et al., 2013a; Shiozawa et al., 2014). A key barrier to the widespread use of tDCS for this common disorder is the requirement to travel to a treatment center for multiple sessions as repeated treatment sessions, typically given on consecutive weekdays over several weeks, are often required to optimize clinical response. For example, the Loo et al. (2012) study suggested that extension of the treatment period from three to 6 weeks resulted in greater clinical improvement. After the acute treatment course, ongoing “maintenance” tDCS, given weekly to fortnightly, has also been reported to be useful in maintaining improvement gained in the acute phase and preventing relapse of depression (Martin et al., 2013a).

Several specific issues need to be considered when applying tDCS in depression trials:

• - An important precaution in this patient group is suicide risk, which may fluctuate from day to day and should be closely monitored. It is unknown if tDCS may lead to increased suicide risk early in the treatment course (as has been proposed with antidepressant medications), either due to improved motivation, or specific treatment-related effects.

• - Dose-control, i.e., control of access and restriction of stimulation to pre-programmed stimulation is important as a safeguard so that the device cannot be used for deliberate self-harm.

• - The research team should closely monitor fluctuations in mental state, which may impinge on the subject’s ability to adequately perform the tDCS procedure at home, for example, due to changes in motivation or concentration. Thus, it is possible that a subject initially assessed as capable of performing remotely supervised tDCS at home, later becomes unable to adequately continue treatment at home—contingencies should be made for this event. Conversely, given findings that tDCS improves information processing speed in depressed patients (Loo et al., 2012) it is also possible that subjects initially assessed as not capable of performing remotely supervised tDCS at home, who may need to commence acute treatment at the treatment center, may later be able to continue the acute treatment course and ongoing maintenance treatments at home under supervision.

• - As part of the initial assessment of suitability for home-based, remotely supervised tDCS, a thorough psychiatric assessment by an experienced clinician is required, evaluating not only mood, but also personality style, current stressors and social and family support. All of these factors should be considered in evaluating a person’s ability to comply with tDCS procedures, likely fluctuations in mental state and risk.

• - The majority of depressed patients presenting for treatment are likely to be on a combination of psychotropic medications, including antidepressants, atypical antipsychotics, anxiolytics, lithium and anticonvulsant mood stabilizers. Further, alterations in concurrent medication treatment may occur frequently common in order to manage side effects, achieve better antidepressant response or provide symptomatic relief (e.g., sleep, anxiety). As there is evidence that anticonvulsant and benzodiazepine medications may affect the efficacy of tDCS, these medications are best avoided if possible. The tDCS team should maintain close liaison with the subject’s treating doctor(s) throughout the tDCS treatment course, to optimize concurrent medications and to establish procedures for clear and prompt communication about any alterations in medications.

Multiple Sclerosis (MS)

For those living with MS, treatments using tDCS have the potential to directly alleviate common yet refractory symptoms including pain, fatigue, depression, and sensory and motor dysfunction (Palm et al., 2014). An important first step is to establish the procedures for feasible at home use, with consideration of potential motor and cognitive impairments.

For this patient population, the emphasis is on extensive and ongoing screening procedures, as well as streamlined and simplified equipment design and set up. To ensure compliance, safety, and assist with training, a secure, daily video monitoring protocol should be implemented.

Further recommendations for MS protocols include the following:

• - Screening is an important first step as remotely-supervised tDCS will not be appropriate for all MS patients. A treating neurologist should ensure that the subject has potential suitability for operating the headgear and device. This would include cutoffs for minimal neurological (motor) and cognitive function. For instance, severe motor impairment can be screened for using the Expanded Disability Status Scale (EDSS) score (Kurtzke, 1983), excluding those with scores of 6.5 or greater. In addition, subjects should be excluded from a remotely-supervised protocol if any visual, auditory, or motor deficits prevent the ability to understand the study instructions or operate the device or laptop computer (Figures ​(Figures1,1, ​,3).3). Minimal cognitive ability for participation could also be defined, for example by establishing cutoffs using the Brief International Cognitive Assessment in MS (BICAMS; Benedict et al., 2012) to exclude those with severe cognitive deficits.

• - The study device should be simple to operate and engineered to unlock single tDCS sessions through a one-time use passcode. Headgear should also be simplified for use. For example, headgear should be modified with a hat-like design to ensure minimal motor requirements. In addition, device kits should be prepared and organized to ensure maximal ease in terms of sponge pocket set-up and daily materials.

• - Clinical and research staff should be trained through a study technician manual on the device setup (programming sessions, retrieving session codes), headgear placement, and subject interactions (requirements for a successful session, items that qualify as “stop” criteria, and troubleshooting). In addition, research staff should be trained on how to safely abort a subject session and on procedures to reestablish video connection if lost.

• - Subject training should occur during an initial in-person training session where each subject will view an instructional video, practice the technique in full and ultimately complete their first tDCS session. Beyond training, these initial visits will ensure inclusion and exclusion criteria are met. Subjects must have a suitable home environment (e.g., distraction free location and space to complete the sessions) access to internet, and the ability to commit to tDCS sessions.

• - An instructional video should support training and implementation, be accessible to the subject throughout the study, and cover all details necessary to complete a session. The video should contain information on general materials, a step by step guide to set up the device, how to abort a session in case of emergency, and the means of properly ending a session and disposing of materials.

• - Stop criteria (assessed at baseline, during sessions, and at follow-up) should be used as a gateway for the subject to proceed at each step (Figure ​(Figure3).3). The protocol should be designed with a series of checkpoints to be met to address compliance (attendance, ability to complete the procedures as instructed, following study guidelines) and tolerability (at any time if any predefined events are reported or if pain crosses a threshold).