rapid removal of the coil from the patient; and. The scope of this document is limited to the repetitive transcranial magnetic stimulation (rTMS) system, (21 CFR 882.5805 and product code OBP) described below. Food and Drug Administration 1061, (HFA-305), Rockville, MD 20852. You should describe the method used by your device to recall treatment history, such as prior patient treatment settings. In addition, the number and incidence of deaths, suicides, seizures or worsening of depression should be provided. rTMS (repetitive transcranial magnetic stimulation) has been shown to produce changes in neuronal activity in regions of the brain implicated in mood regulation, such as the prefrontal cortex. Testing should include the magnitude of the field in the area of the stimulation volume, near the coil surfaces, and areas where there may be local field maxima outside the intended stimulation volume. You should identify all salient features of the waveform (e.g., pulse width) and specify the horizontal and vertical oscilloscope gain settings. You should include a description of the design features and components incorporated into the device to prevent overheating. Therefore, if you have documentation to support the identical nature of the materials, we recommend the following statement for biocompatibility certification of previously used materials: The [polymer/metal/ceramic/composite name] [component name] of the [subject device name] is identical to the [component name] of the [predicate device name] as it was approved/cleared in [PMA/510k/IDE number, approval date] in formulation, processing, and sterilization, and no other chemicals have been added (e.g., plasticizers, fillers, color additives, cleaning agents, mold release agents, etc.). Sponsors must conduct clinical studies in compliance with 21 CFR parts 50, 56, and 812. We recommend you describe the physical characteristics of the magnetic field produced by your device and compare them to those of the predicate device. For depression studies, we recommend that you report change as a continuous measure, as well as the rate of response, defined as a 50% reduction on the assessment scale, and also the rate of remission. This may include patients with these characteristics: Labeling should include a precaution that hearing protection is required during the use of rTMS devices. Clinical Information. 4http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080735.htm, 5http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm089543.htm. non-invasive, directly manipulates brain activity, and can infer causality. You should also include a description of the method used for these measurements and how they have been validated. Validated depression assessment scales should be used as the primary endpoint. baseline depression severity, based on validated depression scale. Treatment parameters that exceed those prescribed in Table 2 will require adequate justification and risk assessment. To request the Agency’s review of your protocols, you can submit a pre-submission to the Agency. Supporting information to substantiate an adequate level of training should be provided, such as a pre-study reliability certification program and reliability assessment for clinical raters during the study. Motor Threshold (MT)/MT Intensity: The motor threshold level is the minimum stimulator setting, in Standard Motor Threshold (SMT) units, that induces an observable motor response by the patient in 50% of the applied pulses, usually as observed by movement of the thumb. the location of the test report in the submission. In addition, other sections of this special control guidance document list the risks to health identified by FDA and describe measures that, when followed and combined with the general controls, will generally address the risks associated with rTMS systems for the treatment of MDD and lead to a timely 510(k) review. For the purposes of this guidance document, the following definitions and recommendations for measurement are used: Frequency: The number of pulses per second expressed in Hertz (Hz). The .gov means it’s official.Federal government websites often end in .gov or .mil. Diabetes mellitus is a clinical syndrome characterized by hyperglycemia caused by respective or absolute deficiency of insulin. The warnings section of the operator’s manual should address the concerns described below. Endpoints should be chosen to assure a clinically meaningful effect. Dr. Tanner can go over all of your questions and concerns about TMS treatment and therapy. The labeling should instruct the prescribing physician to screen each patient for the presence of these devices. Blog. When applying rTMS, a coil is put at a precise and particular location on the head. As-treated, although similar to intent-to-treat, refers to all patients, but is grouped according to the treatment actually received not the randomization assignment. Frequency: 10 Hz In the above FDA approved protocol, the number is 75 times. We recommend that the rTMS device have features that allow: Users of the device should monitor patients for seizures by: Instructions for seizure management procedures should include: The labeling should include an indication for use that is consistent with that described in 21 CFR 882.5805 (see Section 2. Scope). The following study design features should be stated clearly in the study protocol document. This process may help ensure that any issues are addressed prior to submitting your premarket submission. Your statistical hypothesis should describe the specific statistical model proposed for the main analysis and any relevant secondary analyses. We recommend you include the following: You should select biocompatibility tests appropriate for the duration and nature of contact with your device. A rTMS system is an electromagnetic device that non-invasively delivers a rapidly pulsed magnetic field to the cerebral cortex in order to activate neurons within a limited volume without inducing a seizure. FDA recommends you provide details about whether treatment sessions will be individualized (i.e., whether treatment parameters will be adjusted based on the study subject response). You should provide a description and comparison of the following to the predicate device: We recommend you provide oscilloscope tracings of the signal magnetic output waveform (with the applicator attached) over the device’s range of output settings (including minimum, maximum, and a sampling of intermediate settings). Magnetic Field Strength: Magnetic field strength is expressed as B, the magnetic flux density, in units of Tesla. The single pulse machine was first described by Barker et al. a clear summary of all EMC testing (emissions and immunity) of this device with the test results and data to support any claims for immunity to electromagnetic interference (EMI); a brief explanation of how each EMC test was performed and how the testing for each mode addresses the risks for EMI and demonstrates EMC to the claimed levels; a brief explanation of how the testing addresses the timing of the device for therapy delivery; references to appropriate EMC testing standards (e.g., FDA-recognized, IEC 60601-1-2:2001 Standard for Medical Electrical Equipment) along with explanations and justifications for any deviations from the referenced standards or modifications to the device tested; pass/fail criteria for each EMC tests, how these were quantified and measured, and justifications for these criteria. treatment is recommended by health professionals for the early treatment of bone injury or acute soft tissue injuries such as a sprain or strain. You should specify the number and frequency of treatments and overall duration of treatment exposure. If such an interaction term is found to be statistically significant, your statistical summary should include a discussion of the implication of the statistically significant interaction on the overall interpretation of the study results. “Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996,” Electroencephalography and clinical Neurophysiology 108 (1998) 1–16. This discussion should also describe how you have ensured positioning consistency and repeatability. The FDA approved treatment protocol for rTMS is the following: Intensity: 120% of motor threshold The procedure for determining MT location should result in a reproducible and accurate MT location in order to ensure reliable MT level setting and, if used to identify the treatment location, to provide repeatable navigation for treatment when performed by different clinicians. Non-clinical Analysis and Testing, Hazards associated with electrical equipment, Hazards caused by electromagnetic interference and electrostatic discharge hazards, Physical unit of amplitude setting (e.g., coil current, peak magnetic field) at coil and its relation to the SMT unit. This guidance document was developed as a special controls guidance to support the classification of Repetitive Transcranial Magnetic Stimulation (r TMS) systems for the treatment of Major Depressive Disorder (MDD) into class II (special controls). In addition, your statistical analysis section should include a discussion of the importance of any statistically significant treatment-by-site interaction to the overall interpretation of the study results. RTMS high accuracy performance is not affected by precipitation of any kind, vibration and lighting conditions. We recommend that you submit the information for software-controlled devices described in Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices (the Software Guidance).5 The kind of information we recommend you submit is determined by the “level of concern,” which is related to the risks associated with software failure. rTMS This is commonly abbreviated to just “TMS” but technically the ‘r’ is added to convey that the stimulation received is repetitive. A repetitive transcranial magnetic stimulation (rTMS) system is an external device that delivers repetitive pulsed magnetic fields of sufficient magnitude to induce neural action potentials in the prefrontal cortex to treat the symptoms of major depressive disorder (MDD) without inducing seizure in patients who have failed at least one antidepressant medication and are currently not on any antidepressant therapy. You should include an overall assessment of safety and effectiveness. The labeling should state that patients who have a history of seizure, or potential alteration in seizure threshold, should be closely monitored when the device is used. If any test failures were identified and samples of the device modified as a result, you should provide the results from the new testing with the modified samples. If you would like to get started, you can find our contact  information here. rTMS devices are contraindicated for use in patients who have active or inactive implants (including device leads), including deep brain stimulators, cochlear implants, and vagus nerve stimulators. 1Format for Traditional and Abbreviated 510(k)s. 2 Wassermann, E, et al. prior treatment with antidepressant therapies. a complete listing and description of all of the device components and accessories (e.g., console, treatment coil, user interfaces, data management systems, cables). Therefore, recall of previous treatment settings is important for delivery of the appropriate rTMS treatment at the correct location. The labeling should indicate that seizure is a potential risk of treatment with rTMS devices. Pulse Width: When your rTMS output is a damped sinusoidal wave, the pulse width is defined as the time (duration) from the initial peak to next peak of the wave; it is also described as the period of the sinusoidal wave. Electroenceph Clin Neurophysiol Supp 1999; 52:97-103. The pick-up loop for making this measurement should be located at the same distance from the coil as the target tissue in the brain. Before sharing sensitive information, make sure you're on a federal government site. FDA also recommends that the adequacy of blinding be assessed. 3 The recommended maximum train duration (in seconds) for healthy adults for the intensity (% of Motor Threshold) levels and frequencies are shown in Table 2. risk of suicide, based on a validated suicide severity scale. For any covariate term included in the proposed statistical model to evaluate effectiveness, we recommend you investigate a treatment group by covariate interaction. In your assessment you should report: Analysis populations: The preferred analysis population for a superiority study is the intent-to-treat population, consisting of all subjects as originally randomized. If you would like to schedule for a free consultation with Dr. Tanner to discuss how TMS can benefit you, then please give us a call to schedule this. FDA believes that the software used to operate a rTMS device presents a “moderate level of concern” as described in the Software Guidance because a failure or latent design flaw could either directly result in minor injury to the patient or operator or could indirectly result in minor injury to the patient or operator through incorrect or delayed information or through the action of a care provider. If your device relies on motor threshold (MT) for determining the magnitude of the output, you should describe the design features that are used for positioning the coil for locating the MT position and how you have ensured its positioning repeatability. If the output parameters (amplitude, frequency, train duration) of your device exceed these established limits and exceed those of the predicate device, you should provide further evidence of safety that may include clinical data. The site is secure. It is also unaffected by the type and quality of road pavement • Self-contained RTMS does not require auxiliary equipment (e.g. Due to safety concerns, we recommend you exclude subjects who have any metal implanted in the head (except the mouth), e.g., subjects with cochlear implants, implanted brain stimulators, ocular implants, aneurysm clips or stents. So, this is why the ‘r’ is added to TMS to create rTMS. Contraindicated use could result in serious injury or death. Clinical testing will generally be needed for new devices, unless the proposed device is sufficiently similar to the predicate device in terms of indications, device specifications, and energy output, such that reliance on bench and/or animal testing may be sufficient. In addition, you should supplement the oscilloscope tracings with a graphical representation of the output waveform with all stimulation parameters and temporal characteristics clearly labeled. Multiple baseline depression assessments should also be performed to assure that the subject’s depression has stabilized. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. Identify all comments with the docket number listed in the notice of availability that publishes in the Federal Register. When withdrawing subjects from antidepressant therapies, you should follow the drug manufacturer’s labeling regarding the time period that is necessary to assure that the antidepressant medications has been washed out. Patient labeling should describe the alternative treatments such as medications, psychotherapy, and electroconvulsive therapy. Center for Devices and Radiological Health, Office of Device Evaluation You should define your stimulation volume as the region within the Standard Motor Threshold (SMT) set at 1.0. Painful neuropathy in diabetic population is popular, impacting numerous chronic diabetic patients. Example of a Device and Predicate Comparison. As each magnetic pulse passes through the skull and into the brain, this induces brief activity of brain cells underlying the treatment coil. This should be included in the device labeling. Pre-Submission to the patient ; and and effectiveness as treated analyses treated analyses terms effects may be difficult the. 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