MANIFESTO


Subject:  Opposition to EU Reclassification of TMS and tDCS equipment to Class III devices based on flawed evidence

Webinar was organized on January 27th, 2023 

 5:30 pm CET

An summary will be soon available

 

The European Society for Brain Stimulation (ESBS) is an independent and professional association of medical doctors, psychologists, neuroscientists, and others practising and interested in Non-Invasive Brain Stimulation (NIBS) techniques such as repetitive transcranial magnetic stimulation (rTMS) and direct current stimulation (tDCS). Our mission is to promote public and accessible health care, research, and training in the field of brain stimulation and to foster the dissemination of knowledge about brain stimulation to clinicians, researchers, patients and governmental bodies such as the Notified Bodies of EU countries. Our aim is to provide independent and factual up-to-date information about the field of non-invasive brain stimulation. In all of our research and clinical applications, the safety of our patients and research participants has the highest priority. Therefore, we give guidance to stakeholders (policy-makers, manufacturers, researchers, health care providers) on how to improve patient safety and advise them to use only certified medical products. 

 

It has recently come to our attention that the EU has reclassified the NIBS equipments including rTMS and tDCS, as Class III devices, the category of highest risk, similar to invasive treatments, such as deep-brain stimulation implants. This reclassification has a major impact on our field, not only for manufacturers, but also for researchers, clinicians and patients and we judge this reclassification a mistake. First, the evidential basis for this change is a flawed assessment of the safety literature. Second, the consultation process has occurred without input from specialists or stakeholders professionally active in the field of NIBS. Neither the ESBS nor National Societies of Brain Stimulation nor individual experts within the European NIBS community were consulted on this change. Third, this decision will ultimately make NIBS treatment less accessible to patients and will hamper research and development for neuroscience and for new clinical indications. We explain this in detail below. This manifesto is also a call to action. You (whether a researcher, clinician, manufacturer or concerned citizen) can still act, by sending a letter of concern to EU representatives.

 

As a community, we have by now almost 30 years of experience using NIBS technologies for research and clinical applications. Data acquired over this period has been collected to carefully assess the behavioral, neurocognitive, physiological, and biophysical effects on the central nervous system. These studies have not only informed us about the clinical efficacy of NIBS and resulted in new evidence-based non-pharmacological treatments for neurological and psychiatric disorders that are used in a growing number of countries worldwide, but have also informed us about the risks, adverse and side effects that can occur when applying NIBS to the human brain. Based on this vast amount of safety data collected over the past 30 years, several publications, meta-analyses, reviews, guidelines and consensus papers have provided peer-reviewed evidence-based assessments of the safety of TMS (see e.g., Rossi et al., 2020) as well as low output transcranial electric stimulation, TES (see e.g., Antal et al., 2017; 2022; Bikson et al., 2018a; b; Caulfield et al., 2022; Zewdie et al., 2020). Based on these data, the current scientific and clinical evidence suggests both rTMS and low intensity TES are safe treatment and research interventions with few and mild adverse effects. 

 

Although this new reclassification currently refers only to “products without an intended medical purpose”, the evidence adduced about the risks and adverse effects of rTMS and TES, - which serves as the justification for this reclassification-, is gravely flawed. The EU has apparently assessed that NIBS poses a greater risk to patients' safety than previously thought. This assessment is based on incorrect statements about rTMS and low intensity TES that are contradictory to the available scientific evidence, and many of the stated claims and assumptions are false (e.g., it is claimed that TMS/TES can induce “atypical brain development” or “abnormal patterns of brain activity”). Likewise, the prominent mentioning of rTMS/TES-related seizure risks contradicts the most recent consensus statement in the field based on actual clinical data which demonstrated that observed seizure rates are so much lower than previous guidelines advised, that the prior caution about seizure risk is no longer supported by scientific evidence (Rossi et al., 2020). To put this into perspective, the likelihood of a seizure from rTMS (0.003%) is lower than that associated with the use of antidepressants and antipsychotics (0.1-1, 5%), which are one of the most frequently prescribed treatments for depression (George et al., 2013). Moreover, when such seizures occur they do so mostly outside the clinician’s office, by contrast with rTMS (Perera et al., 2016). For low intensity tDCS, tACS, tRNS seizure risk is completely absent. 

 

As an organisation and representatives of NIBS clinicians and professionals from across Europe, we, the ESBS, therefore disagree with this EU decision and in particular with the factually incorrect justifications of that decision to reclassify TMS and TES as invasive technologies that require medical class-III classification. The impact of this reclassification will result in higher costs, lower accessibility for patients to treatment and substantial delays in NIBS development for new clinical and research indications. We agree that all transcranial brain stimulation devices must be certified medical devices, class IIa, to be used clinically only under supervision of a clinician and trained personnel, and used in basic research after approval of a local ethical committee. However, to reclassify NIBS devices as having the same level of risk as invasive brain stimulation devices that are implanted inside the brain, is inappropriate, contradicts 30 years of safety data, and has been decided without consultation of relevant professionals. 

 

Therefore, if you are in agreement with the concerns stated above, we kindly ask you to protest this decision by sending an email to sante-med-dev@ec.europa.euHere you can find suggested text for your email. Please feel free to modify it.  Note: it is our understanding that the greater the number of individual emails that are sent in protest, the greater the likely impact. So please send an email on your own behalf and disseminate widely across your network of NIBS colleagues in order to maximize impact. 

 

C. Baeken, president & A. Antal, vice-president

on behalf to the  European Society of Brain Stimulation (ESBS)

 

 

References:

Antal A, Alekseichuk I, Bikson M, Brockmöller J, Brunoni AR, Chen R, Cohen LG, Dowthwaite G, Ellrich J, Flöel A, Fregni F, George MS, Hamilton R, Haueisen J, Herrmann CS, Hummel FC, Lefaucheur JP, Liebetanz D, Loo CK, McCaig CD, Miniussi C, Miranda PC, Moliadze V, Nitsche MA, Nowak R, Padberg F, Pascual-Leone A, Poppendieck W, Priori A, Rossi S, Rossini PM, Rothwell J, Rueger MA, Ruffini G, Schellhorn K, Siebner HR, Ugawa Y, Wexler A, Ziemann U, Hallett M, Paulus W. Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol. 2017;128(9):1774-1809. doi: 10.1016/j.clinph.2017.06.001

 

Antal A, Luber B, Brem AK, Bikson M, Brunoni AR, Cohen Kadosh R, Dubljević V, Fecteau S, Ferreri F, Flöel A, Hallett M, Hamilton RH, Herrmann CS, Lavidor M, Loo C, Lustenberger C, Machado S, Miniussi C, Moliadze V, Nitsche MA, Rossi S, Rossini PM, Santarnecchi E, Seeck M, Thut G, Turi Z, Ugawa Y, Venkatasubramanian G, Wenderoth N, Wexler A, Ziemann U, Paulus W. Non-invasive brain stimulation and neuroenhancement.  Clin Neurophysiol Pract. 2022;7:146-165. doi: 10.1016/j.cnp.2022.05.002

 

Bikson M, Paneri B, Mourdoukoutas A, Esmaeilpour Z, Badran BW, Azzam R, Adair D, Datta A, Fang XH, Wingeier B, Chao D, Alonso-Alonso M, Lee K, Knotkova H, Woods AJ, Hagedorn D, Jeffery D, Giordano J, Tyler WJ.Limited output transcranial electrical stimulation (LOTES-2017): Engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk. Brain Stimul. 2018a;11(1):134-157. doi: 10.1016/j.brs.2017.10.012

 

Bikson M, Brunoni AR, Charvet LE, Clark VP, Cohen LG, Deng ZD, Dmochowski J, Edwards DJ, Frohlich F, Kappenman ES, Lim KO, Loo C, Mantovani A, McMullen DP, Parra LC, Pearson M, Richardson JD, Rumsey JM, Sehatpour P, Sommers D, Unal G, Wassermann EM, Woods AJ, Lisanby SH. Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop. Brain Stimul. 2018b;11(3):465-480. doi: 10.1016/j.brs.2017.12.008

 

Caulfield KA, Fleischmann HH, George MS, McTeague LM. A transdiagnostic review of safety, efficacy, and parameter space in accelerated transcranial magnetic stimulation. J Psychiatr Res. 2022;152:384-396. doi: 10.1016/j.jpsychires.2022.06.038

 

George MS, Taylor JJ, Short EB. The expanding evidence base for rTMS treatment of depression. Curr Opin Psychiatry. 2013;26(1):13-8. doi: 10.1097/YCO.0b013e32835ab46d

 

Perera T, George MS, Grammer G, Janicak PG, Pascual-Leone A, Wirecki TS. The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder. Brain Stimul. 2016;9(3):336-346. doi: 10.1016/j.brs.2016.03.010.

 

Rossi S, Antal A, Bestmann S, Bikson M, Brewer C, Brockmöller J, Carpenter LL, Cincotta M, Chen R, Daskalakis JD, Di Lazzaro V, Fox MD, George MS, Gilbert D, Kimiskidis VK, Koch G, Ilmoniemi RJ, Lefaucheur JP, Leocani L, Lisanby SH, Miniussi C, Padberg F, Pascual-Leone A, Paulus W, Peterchev AV, Quartarone A, Rotenberg A, Rothwell J, Rossini PM, Santarnecchi E, Shafi MM, Siebner HR, Ugawa Y, Wassermann EM, Zangen A, Ziemann U, Hallett M; Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines. Clin Neurophysiol. 2021;132(1):269-306. doi: 10.1016/j.clinph.2020.10.003. 

 

Zewdie E, Ciechanski P, Kuo HC, Giuffre A, Kahl C, King R, Cole L, Godfrey H, Seeger T, Swansburg R, Damji O, Rajapakse T, Hodge J, Nelson S, Selby B, Gan L, Jadavji Z, Larson JR, MacMaster F, Yang JF, Barlow K, Gorassini M, Brunton K, Kirton A. Safety and tolerability of transcranial magnetic and direct current stimulation in children: Prospective single center evidence from 3.5 million stimulations. Brain Stimul. 2020;13(3):565-575. doi: 10.1016/j.brs.2019.12.025