CBS Standard Operations Procedure (SOP) (NU login)
The purpose of this document is to instruct how to use TMS for research at Center for Brain Stimulation (CBS). The instructions for TMS are quite similar to other imaging modalities at RIC/NU, and their purpose is to maximize safety for subjects and experimenters. This manual is created and updated by the CBS Laboratory Committee.
A. Accreditation and training. Each new prospective TMS user must participate in the CBS 1-Day Basic TMS Safety Course. Successful completion of this course is a prerequisite for gaining access to our TMS laboratory, and will lead to accreditation at the Basic Level (white badge). Since this course includes environment specific information, all users regardless of previous TMS expertise need to participate. Those wishing to take their accreditation to the Advanced Level (blue badge) must show written proof of extensive TMS training and experience, and additionally observe 10 TMS sessions and then conduct 10 supervised sessions. All levels additionally require proof of Basic Life Support (BLS) or corresponding medical training.
B. Background information. Each investigator wishing to use TMS needs to read the following documents (discussed at the 1-Day Safety Course):
- Rossi S, Hallet M, Rossini PM, Pascual-Leone A (2009) Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 120(12):2008-39.
- RIC TMS Safety Guidelines
- RIC TMS Screening Form
C. Safety Review by the CBS Laboratory Committee. Based on Rossi et al. (2009) the PI will (a) classify the study as Risk Class 1, Class 2, or Class 3; (b) determine if a covering MD is needed; and (c) perform a risk/benefit analysis showing that any possible risk is justified. The PI will submit the Safety Review Form to the CBS Laboratory Committee (CBS@ric.org) that will approve or suggest modifications as needed.
D. NU IRB and FDA IDE Review(s). After receiving approval of the Safety Review, the PI will submit a NU IRB application. Studies that involve non-significant risk require only IRB approval. Studies that involve significant risk may additionally require FDA IDE (applying for an IDE may be a lengthy and intensive process).
E. Requesting a TMS account. After receiving Safety Review and IRB (and potentially FDA IDE) approvals the PI submits a copy of the approval letters to the CBS Administrator (CBS@ric.org) and requests a TMS account. Once the request is approved, the PI will receive an account code for reserving and billing for TMS time. Unfunded studies that need to collect limited amounts of pilot data for grant applications may apply for a Pilot Account.
F. Reserving TMS time slots. Regular access during tech-supported hours (weekdays 8 am - 4 pm) follows the online TMS Schedule calendar. The PIs are invited to submit instrument time requests to CBS (CBS@ric.org) at the beginning of their project. The CBS will strive to ensure that all researchers are granted at least an equitable access minimum, appropriate to their needs, regardless of priority. NIH-funded projects participating in the instrumentation grant that funds the system receive priority in scheduling. Second priority will go to other NIH-funded projects not included in the grant, followed by other, non-NIH funded (e.g., NSF, DoD/DARPA), and unfunded pilot projects. Additional instrument time without tech support is available at 4 pm - 10 pm weekdays and 8 am - 10 pm on weekends; these unscheduled time slots are reserved on the online TMS Scanner Schedule pages by the users directly. Some slots will be reserved for maintenance, quality assurance, and safety training. The RIC CBS Administration reserves the right to change the schedule as needed.
G. Use it or lose it. Negligence or misconduct in managing instrument time will lead to loss of instrument privileges. Cancellations and no-shows need to be handled promptly. For cancellations the team has to remove their reservation from the online TMS Schedule at least 24 hours before the time slot or the reserved instrument time will be charged in full. Same-day cancellations (e.g., subject no-shows) need to be reported at the onset of the time slot to TMS Administration (CBS@ric.org) and the online TMS Schedule. Projects that request more instrument time than what they use and/or repeatedly fail to handle cancellations and no-shows will be given less slots or denied access.
H. Consent/TMS Safety Screening Forms. Before a TMS session, document the consent of the subject by going through and signing the IRB approved consent form with the subject. Thereafter, ask the subject to fill in the IRB approved TMS Safety Screening Form, and sign the form with the subject. Once you have confirmed that none of the answers on the Safety Screening Form raise concerns, you are allowed to start the session. After the session, drop copies of the cover and signature pages of the IRB consent form and the TMS Safety Screening Form in the locked mailbox at the TMS front desk.
I. Pregnancy. Healthy subjects may not receive TMS for research purposes while pregnant. This also applies to pregnant patients, unless they are in the study population, the additional risks and benefits are ethically justified through potential for direct benefit to the patient, the study is IRB approved, and potential risks are disclosed to the patient.
Pregnancy in women of child bearing potential is typically excluded with a questionnaire. Specifically, the investigator will document the subject’s responses to these questions in the Safety Screening Form:
- Do you believe that you could be pregnant? Yes/No
- Are you currently trying to become pregnant? Yes/No
- Are you using reliable contraception? Yes/No
- When did your last period start? Date:_______
Pregnancy may be excluded if answers to the above questions indicate that the subject is not pregnant. If the subject thinks she could be pregnant, or answers to these questions suggest pregnancy is possible, a urine pregnancy test prior to the TMS session is needed to rule out pregnancy.
J. Hearing protection. The clicks coming from the TMS coil are loud enough to temporarily elevate hearing thresholds. During TMS the subject needs to use hearing protection (e.g., earplugs). We also recommend hearing protection for study personnel near the TMS device.
K. Personnel during TMS sessions. During TMS delivery at least two researchers must be present at all times. The person operating the TMS instruments ("Operator") must have Advanced Level training (this can be the CBS TMS/EEG Tech). The second researcher ("Investigator") can have either Basic or Advanced Level training. Personnel without TMS badges are not allowed in the laboratory during TMS. The IRB/FDA IDE protocol may additionally require medical equipment (e.g., code cart) and/or a Covering MD to be present.
L. Use correct TMS parameters and correct subjects. Using too high frequencies for too long and/or at too high intensities strongly increases the risk for serious side effects. The Operator is responsible for knowing the published safety limits (Rossi et al. 2009), for using only TMS sequences and intensities listed in the protocol, and setting these parameters correctly into the TMS stimulator. The Investigator is responsible for ensuring that the subject matches the protocol requirements and does not have contraindications for TMS or conditions that increase risk for serious side effects (unless these are justified by the risk/benefit analysis, allowed by the protocol, and disclosed to the subject).
M. Observe the subject during TMS. If the subject is uncomfortable, make adjustments until the problem is solved. If this cannot be done, terminate the experiment. Keep a constant eye on the subject and if any sign of spread of activation is observed or you suspect a focal or generalized seizure, stop TMS immediately and follow the TMS Seizure Plan (paragraph 13 in the RIC/NU TMS Safety Guidelines; see also below).
N. Observe the subject after TMS. After stopping TMS keep the subject at RIC until all behavioral effects of TMS have disappeared. For single and dual pulse studies this happens immediately. For rTMS this may take up to 30 minutes. For unconventional sequences (theta burst, quadripulse) this may take up to 70 minutes.
O. Clean up. Shut down the equipment and remove trash. Return coils in their boxes to the closet, clean and organize, and store EEG/EMG electrodes and leads. Return stimulators, navigators, and other carts to their places.
P. Malfunctions and broken equipment. You must report these immediately (CBS@ric.org). Broken equipment is useless and can be dangerous.
Q. START and END inspections of the coils. For every TMS session, the Operator is responsible for visually inspecting the coil and its reflectors at the start and end of the measurement. Failure to do this will result in loss of TMS time slots and privileges for the responsible group. The TMS coils and especially the navigation reflectors attached to them are the most sensitive part of the TMS system. Handle them with extreme care and do not touch the reflectors with bare hands or let them touch anything else. Dropping a coil may render it unsafe to use. Even slightly knocking the reflector holder may severely degrade navigation accuracy. Report all instances immediately (CBS@ric.org) as these require inspection and/or calibration.
R. Treating adverse events and side effects. All serious adverse events and side effects must follow the TMS Seizure Plan (see below). For mild adverse events the PI must decide if they require treatment and/or follow-up (if needed, consult Covering MD, or if the protocol does not have one, contact email@example.com).
S. Reporting adverse events and side effects. All serious adverse events must be immediately reported by the PI to the CBS Laboratory Committee and to the NU IRB. All adverse events and expected side effects that are not serious are recorded by the PI and reported to the CBS Laboratory Committee every 3 months, in addition to other reporting requirements to NU IRB. Additional reporting requirements to FDA IDE may apply as indicated in the protocols.
EMERGENCIES. In all emergencies follow the TMS Seizure Plan:
In the event of a suspected partial or generalized seizure, the TMS Operator immediately stops TMS, and the Operator and Investigator together keep the subject from hurting him/herself during convulsions (that typically last less than 90 seconds), secure an open airway without putting anything in the mouth, and clock the seizure onset. Once instructed by the Operator, the Investigator will call the in-house medical response emergency team that includes the resident-on-call ("ROC STAT"). For significant risk studies, the Investigator will also alert the Covering MD to arrive to the TMS laboratory immediately. There is no useful anticonvulsive medication that would need to be administered, unless the seizure lasts over 5 minutes. The Operator will continuously monitor the subject until the covering MD and/or emergency medical response team arrive. The only person that may, under specific circumstances, determine that a transfer to the ER is not required is the Covering MD; in all other scenarios the emergency response team must alert RIC security to arrange transfer with an ambulance to the Northwestern Memorial Hospital ER for clinical evaluation. These steps are taken in all suspected seizure events immediately and regardless of rate of recovery of the subject.