Periodic Reporting for period 3 - NEWROFEED (Personalized medical device for the diagnosis and treatment of ADHD based on EEG biomarkers and Neurofeedback Training)
Periodo di rendicontazione: 2017-10-01 al 2018-03-31
Attention Deficit Hyperactivity Disorder (ADHD) is a chronic, debilitating disorder usually diagnosed during childhood impacting negatively many aspects of patients’ lives including: academic achievements, social skills, perception of self-worth and leads to strained parent-child relationships.
The cost of illness has been estimated as being as high as €7,000 per patient per year in the UK (Telford C. et al. - 2012) and the prevalence of the condition in Europe is estimated at 5% of the child population. In other words, 4 million EU children are likely to be suffering from ADHD.
The most common treatment for ADHD is a form of psychoactive medication, and in many cases, methylphenidate (MPH). While these drugs do have a positive impact, leading to short term adaptation of the child’s behavior, they are purely symptomatic. They also have significant side effects, impacting sleep, appetite and sometimes the personality of the child through affective blunting and reduced creativity; consequently, they developed a cultural resistance from users (Berger I, Dor T, Nevo Y, Goldzweig G. -2008).
There is an alternative: personalized brain rehabilitation (PBR). It is a self-paced neuromodulation technique that uses the signals from the brain, collected in real-time using a safe, non-invasive technique called electroencephalography (EEG), to help the patient train brain functions and normalize its activity to a healthy range of functioning. It has been associated with improved outcomes in ADHD children in many controlled studies, which recent meta-analysis pooling those positive results into stronger level of evidence (Micoulaud-Franchi 2013). Some studies have demonstrated that the care delivered via neurofeedback had long-lasting effects: children treated for a few months with NFB remained free of the symptoms 6 months even after having ceased the treatment (Steiner et al.- 2014), a major departure from the symptom-only impact of drugs. Two main issues have hindered the deployment of neurofeedback as a large-scale treatment for ADHD: first of all, the large heterogeneity of technical and methodological implementations in existing trials; second, the lack of a standardized technical implementation for the delivery of neurofeedback.
Recent breakthroughs in EEG hardware and real-time software are finally enabling the development of a fully automated neurofeedback device that would be user-friendly and robust to be used in the home by the patients and their families themselves without a doctor or a therapist present. This is the device we set out to develop and demonstrate through the NEWROFEED project.
The cost of illness has been estimated as being as high as €7,000 per patient per year in the UK (Telford C. et al. - 2012) and the prevalence of the condition in Europe is estimated at 5% of the child population. In other words, 4 million EU children are likely to be suffering from ADHD.
The most common treatment for ADHD is a form of psychoactive medication, and in many cases, methylphenidate (MPH). While these drugs do have a positive impact, leading to short term adaptation of the child’s behavior, they are purely symptomatic. They also have significant side effects, impacting sleep, appetite and sometimes the personality of the child through affective blunting and reduced creativity; consequently, they developed a cultural resistance from users (Berger I, Dor T, Nevo Y, Goldzweig G. -2008).
There is an alternative: personalized brain rehabilitation (PBR). It is a self-paced neuromodulation technique that uses the signals from the brain, collected in real-time using a safe, non-invasive technique called electroencephalography (EEG), to help the patient train brain functions and normalize its activity to a healthy range of functioning. It has been associated with improved outcomes in ADHD children in many controlled studies, which recent meta-analysis pooling those positive results into stronger level of evidence (Micoulaud-Franchi 2013). Some studies have demonstrated that the care delivered via neurofeedback had long-lasting effects: children treated for a few months with NFB remained free of the symptoms 6 months even after having ceased the treatment (Steiner et al.- 2014), a major departure from the symptom-only impact of drugs. Two main issues have hindered the deployment of neurofeedback as a large-scale treatment for ADHD: first of all, the large heterogeneity of technical and methodological implementations in existing trials; second, the lack of a standardized technical implementation for the delivery of neurofeedback.
Recent breakthroughs in EEG hardware and real-time software are finally enabling the development of a fully automated neurofeedback device that would be user-friendly and robust to be used in the home by the patients and their families themselves without a doctor or a therapist present. This is the device we set out to develop and demonstrate through the NEWROFEED project.
In the first year of NEWROFEED, our focus was to finalize the medical device necessary to start enrolling patient in the Randomized Clinical Trial. The three main technical tasks and milestones for the first year of the project were achieved:
• We finalized the specification and implementation of the optimal hardware solution for ADHD@Home.
• We developed the software stack necessary for the real-time extraction of biomarkers and delivered on time a complete, validated, innovative solution, including the front-end sitting on the tablet as well as the back-end sitting on our servers, to the clinicians leading our clinical trial.
• We designed the study protocol necessary to prove the safety and efficacy of our solution in tandem with our Key Opinion Leaders and got the study approved in a number of European countries.
We reached a major milestone right before the end of the first year of NEWROFEED when the first patient was enrolled on August 31, 2016 in one of the French investigation centers.
The second year of the project was focused on three main tasks:
• Managing the enrolment of patients in NEWROFEED and supporting our investigation centers with training and technical and clinical support, while ensuring patient safety;
• Incorporating the feedback from the patients into an optimized version of our neurofeedback platform that we can take to market;
• Starting dissemination and commercialization activities activities, and, in particular, obtain CE marking for our device under the European Directive for medical devices, 93/42/EEC.
We are happy to report that our main goals have been reached and we are excited to be nearing the point at which we will be able to start commercializing our technology. In particular, in a major breakthrough, we received certification for our ADHD product a few days after the end of Year 2: this makes Mensia the only company in Europe with a market-approved digital therapy and commercialization was initiated in Q1 2018.
During the last reporting period (6 months) we concentrated on:
• the completion of our clinical trial mostly focusing our effort in the management of the clinical centers with the help of our CRO to keep enrollment pace;
• the development and regulatory clearance of a new version of our medical device based on user and clinical feedback obtained during the RCT;
• the dissemination of our results and early commercialization efforts;
• the maintenance of or Intellectual Property Rights (IPR) and new CE class IIa certification.
The achievements during the final phase of the project were outstanding. However we could not demonstrate that our device is non-inferior to MPH, we have now solid clinical evidence that is more effective than placebo. At the same time, we completed all the regulatory milestones and released our first orders, so that Mensia Koala™ is now used by patients. Finally, our machine learning analysis paves the way for protocols with improved efficacy leveraging CloudTS, the big data technology developed during this project.
• We finalized the specification and implementation of the optimal hardware solution for ADHD@Home.
• We developed the software stack necessary for the real-time extraction of biomarkers and delivered on time a complete, validated, innovative solution, including the front-end sitting on the tablet as well as the back-end sitting on our servers, to the clinicians leading our clinical trial.
• We designed the study protocol necessary to prove the safety and efficacy of our solution in tandem with our Key Opinion Leaders and got the study approved in a number of European countries.
We reached a major milestone right before the end of the first year of NEWROFEED when the first patient was enrolled on August 31, 2016 in one of the French investigation centers.
The second year of the project was focused on three main tasks:
• Managing the enrolment of patients in NEWROFEED and supporting our investigation centers with training and technical and clinical support, while ensuring patient safety;
• Incorporating the feedback from the patients into an optimized version of our neurofeedback platform that we can take to market;
• Starting dissemination and commercialization activities activities, and, in particular, obtain CE marking for our device under the European Directive for medical devices, 93/42/EEC.
We are happy to report that our main goals have been reached and we are excited to be nearing the point at which we will be able to start commercializing our technology. In particular, in a major breakthrough, we received certification for our ADHD product a few days after the end of Year 2: this makes Mensia the only company in Europe with a market-approved digital therapy and commercialization was initiated in Q1 2018.
During the last reporting period (6 months) we concentrated on:
• the completion of our clinical trial mostly focusing our effort in the management of the clinical centers with the help of our CRO to keep enrollment pace;
• the development and regulatory clearance of a new version of our medical device based on user and clinical feedback obtained during the RCT;
• the dissemination of our results and early commercialization efforts;
• the maintenance of or Intellectual Property Rights (IPR) and new CE class IIa certification.
The achievements during the final phase of the project were outstanding. However we could not demonstrate that our device is non-inferior to MPH, we have now solid clinical evidence that is more effective than placebo. At the same time, we completed all the regulatory milestones and released our first orders, so that Mensia Koala™ is now used by patients. Finally, our machine learning analysis paves the way for protocols with improved efficacy leveraging CloudTS, the big data technology developed during this project.
First, we have demonstrated that research-grade EEG acquisition in the home, with an affordable device, and with support from lightly trained parents is possible. Second, we initially met skepticism when suggesting that ADHD children would comply on their own with the schedule and efforts required by neurofeedback training in the absence of a therapist. We can now report that we have 90% of our patients who use the system at least twice a week, a very good level of compliance. Third, the safety report on the first 140 patients has demonstrated a six fold reduction in side effects compared to MPH users.
In terms of impact, the market has continued to grow at its usual, global pace of 8+%, both in Europe and the US, reaching $11bn in 2015 (source: IMS Health) for ADHD drugs. ADHD is still the number one market for drugs in child psychiatry in the world. The European patient associations we have spoken to have confirmed the view that end users are looking for alternative to pharmacological treatment and would be willing to pay out of their own pockets a large part of the cost of the device while we seek reimbursement. Physicians are looking for alternatives as well: our proprietary research has shown that 90%+ of the health care professionals (all physicians: child psychiatrists, neuro-pediatricians…) we queried declared they would use our product as first line treatment for ADHD children if its equivalence versus MPH and curative effects were proven.
The coming months after the NEWROFEED project will be dedicated to dissemination and commercialization of our product and we expect to sell approximately 50 units over the last semester of 2018. We expect an accumulated sales estimate of €95 million for the next 5 years (starting 2019).
In terms of impact, the market has continued to grow at its usual, global pace of 8+%, both in Europe and the US, reaching $11bn in 2015 (source: IMS Health) for ADHD drugs. ADHD is still the number one market for drugs in child psychiatry in the world. The European patient associations we have spoken to have confirmed the view that end users are looking for alternative to pharmacological treatment and would be willing to pay out of their own pockets a large part of the cost of the device while we seek reimbursement. Physicians are looking for alternatives as well: our proprietary research has shown that 90%+ of the health care professionals (all physicians: child psychiatrists, neuro-pediatricians…) we queried declared they would use our product as first line treatment for ADHD children if its equivalence versus MPH and curative effects were proven.
The coming months after the NEWROFEED project will be dedicated to dissemination and commercialization of our product and we expect to sell approximately 50 units over the last semester of 2018. We expect an accumulated sales estimate of €95 million for the next 5 years (starting 2019).