Final Report Summary - TREM-END (Development of a wrist orthotic device for tremor suppression through biomechanical loading by means of a novel rotary actuator) Executive Summary:The goal of the project Trem_end was to develop a new orthotic device to mechanically reduce the severity of tremor at the upper-limb. In this project, we were performed:• A new damping system capable of reducing vibration• Development of a low-obtrusiveness rotary damper• Development orthesis’ support• A new tremor suppression orthosisWe have achieved several scientific objectives:• Theoretical definition of upper limb tremor• Theoretical definition of damping system with viscous and dry friction• Definition of optimum design criteria of the orthosis supports based on functionality and acceptance requirementsThere is an important orthotic market in Europe, where the proportion of the population aged 65 and over is expected to grow. The Orthosis is an alternative method to reduce essential tremor, this method could help to the Public Health System to reduce the cost of treatment to this collective. We have established a prize of 680 € to sell the orthosis.The exploitation Agreement will gather all the provision for the regulation of exclusive use and distribution rights and will specify at geographical and sectoral delimitations that will apply to these rights. Besides, we have been carried out commercial and scientific/ technological dissemination of the results of this project through mass media, specialized international journals or conferences.Project Context and Objectives:In the EU more than 4.25M people aged 40 and over are affected by Essential Tremor (ET), a progressive neurological disorder who’s most recognizable feature is a tremor of the arms that is apparent during voluntary movements. ET affects the hand in 90% of the cases and, consequently, everyday tasks and those requiring fine motor skills (such as eating and writing) become very difficult for the patients, and this drastically decreases their quality of life (QoL). Medication and surgical interventions are currently employed to reduce tremor in patients suffering from ET. However, both present poor outcomes and, besides being very expensive, both can result in side effects, the major part of which are very debilitating for the patient (e.g. drowsiness, toxic reactions, permanent complications, etc.). As a result of the current poor outcomes, treating patients with ET is still an unsolved problem that drastically affects the Activities of Daily Living (ADLs) and the QoL of approximately 2M European people. During the last years, scientific publications have shown that ET responds to biomechanical loading. It has been clinically proven that the increase of damping and/or inertia in the upper limb leads to a reduction of the tremorous motion, and this led to the development of experimental wearable devices for tremor suppression (orthoses). However, existing concept solutions still present reduced performance and several limitations such as obtrusiveness, weight, and low acceptance among users that have prevented their commercial exploitation. The current project aims at developing a new orthotic device to mechanically reduce the severity of tremor at the upper-limb and acceptable from the users point of view.Project Results:The main S&T results are the following:• Result1 (Deliverable D2.4 Milestone M2): Development of a new damping system capable of reducing tremor provoked by ET. It will combine viscous and dry friction, and will able to achieve at least a 95% tremor reduction at typical vibration exerted by ET (4-8Hz). • Result2 (Deliverable D3.2): Development of a low-obtrusiveness rotary damper. The damping system prototype (Result1) must be embedded into a rotary damper concept design in order to obtain a real scale damper. The final design must fulfil both biomechanical requirements (to achieve tremor suppression) and user-centred design criteria (to increase acceptance).This device will be able to achieve at least 80% tremor suppression, and its reduced obtrusiveness will be validated by users in terms of acceptance.• Result3 (Deliverable D4.2): Development of orthesis’ supports able to maintain the efficacy of the damping system and high acceptability by patients. We will design it according to loads and pressure distribution ensuring that 95% of the designed damping effect proceeding from the rotary damper is maintained. We will apply user-centred design criteria to obtain orthesis’ supports; the end users will validate the aesthetic improvements. • Result4 (Deliverable D5.2 Milestone M3): Integration of orthesis’ supports (Result3) with the developed damper (Result 2) to obtain a new tremor suppression orthesis. We will develop the interconnection systems between orthesis’ supports and damper, and integrate them together to obtain the final product. The final orthesis will reduce at least 70% of tremor from real patients (surgery can reduce tremor by 60-90%. Furthermore, we will validate the acceptance of the product by means of end users tests. In order to enable these technological developments we will therefore establish the knowledge bases delivered through the achievements of the following Scientific Objectives (SO):• SO1 (Deliverable D1.1 Milestone M1): Theoretical definition of upper limb tremor. We will gather current knowledge in biomechanical models of vibration at upper limbs, models that characterize upper limb soft tissues effects and models of tremor activation. Data obtained by these models will provide the needed information for building up a test rig that will support the development of the damping system (Result1). • SO2 (Deliverable D2.1): Theoretical definition of damping system with viscous and dry friction. We will increase understanding of Non-Newtonian fluids working in the frequency domain to select the most suitable fluids for the damping system taking into account SO1. After that, we will develop a theoretical model that will represent behaviour of damping system in order to select the three most suitable fluids. Through this information and data proceeding from Deliverable1.1 we will develop a test rig that will allow testing and developing three damping system prototypes. We will then select the best damping system prototype (Result1) through mechanical tests both in simulated conditions and with real patients, carried out by means of the test rig.• S03 (Deliverable D4.1): Definition of optimum design criteria of the orthosis supports based on functionality and acceptance requirements. We will analyze loads and pressure distribution in patients’ arm in order to establish design criteria for developing supports that will ensure the efficacy of the damper and optimum comfort. Furthermore, we will analyze users’ opinion to fully meet their aesthetical preferences and increase users’ acceptance of the final device. The obtained technical drawings will then allow manufacturing the final supports (Result3) and, once integrated with the other components, the final orthosis (Result4).Potential Impact:Orthotics Market OverviewThe orthotics market represents a quota of 4.6% of the orthopedic market. Unlike other subsectors that consist of few different products that bring in billion dollars each year (e.g. joint replacements), the orthotic market is extremely diverse including many type of products falling under the same umbrella. These can be braces and support systems such as knee braces, knee-ankle braces, knee-ankle-foot braces, wrist braces and other support devices. According to a report by Global Industry Analysts, the orthotics market sector was €1.68 Bn worth worldwide during 2008, and is projected to grow rapidly to €3.45 Bn by 2015. The orthotics sector is currently dominated by Europe and USA, which collectively account for about 70% of the global market of orthotics. Another minor but relevant actor is Japan, with about 10% worldwide market share, whereas the other actors are mainly represented by Asia-Pacific and Latin America areas’ countries.While orthopedics market sectors like “Spine”, Trauma” and “Joint Replacement” are mainly controlled by huge multinational firms producing medical devices (e.g. Stryker, Simmer Holdings, Sofamor Danek, etc.), the European orthotics market is mainly controlled by SMEs. Indeed, according to Eucomed, SMEs make up more than 80% of the medical technology industry in Europe.The orthotics market sector is a very competitive one and its growth projections are due to the ageing population phenomena. In fact, the proportion of the population aged 65 and over is expected to grow from current 84.6M people to 120M by 2030. Consequently, the increasing amount of fractures, joint instability and joint afflictions will increase the demand of various bracing and support systems.Therefore, the increase of the share of population aged 65 and over represents an opportunity for the European SMEs of the orthopedic sector, as the demand for orthopedic products will proportionally increase. However, foreign competitors of the sector, especially U.S companies, have also foreseen these market opportunities. Indeed, a deep penetration by U.S. orthopedic products has been observed during the last years, as for example from 2005-2006 there has been a growth of shipments of U.S. medical devices to EU 27 countries of 7.2%, and a growth of shipments to Eastern Europe countries of 28.7%. In this context, it is important for the European companies of the orthotics sector (mainly SMEs) to stay competitive for both withstanding the foreign competition and taking advantage of emerging market opportunities. Hence, it is important for the SMEs of this sector to focus on application of specific technological advances, with the aim of promoting the creation of effective and innovative products while opening up applications in numerous market niches. The TREM-END project is really committed to achieve this objective as the final device will present several features that contribute not only to solve a huge European societal problem (people suffering from pathological tremor), but also to provide the European SMEs with new capabilities, knowledge and skills to offer new technological products in order to seize timely opportunities and effectively compete with foreign competitors in the orthotics sector.Cost analysis of the TREM-END orthotic system and assessment of the potential impactIn order to estimate the potential market for the TREM-END concept, it is first important to assess the burden of essential tremor in Europe. It is estimated that over 4.25M people in Europe aged 40 and over (2% of people aged 40 and over) suffer from essential tremor, which affects the hand in 90% of the cases (3.8M people). Of this group, there are about 2.2M people that have to deal with severe limitations while carrying out the activities of daily living because there is no treatment for their problem due to one or more of the following reasons:• medication is not effective: about 50% of the cases;• medication has heavy side effects which require discontinuation: about 20% of patients;• surgical intervention is not recommended due to heavy side effects: for example in Thalamotomy over 15% of patients present permanent complications, whereas speech difficulties are reported in 25% of cases.• surgical intervention is not effective: e.g. in 17% of patients treated with Thalamotomy;• surgical intervention losses effect: e.g. in 16% of patients treated with DBS, after 40 months.In conclusion, it is estimated that over 50% of people aged 40 and over (2.2M) live without an effective solution for their pathology. This situation will dramatically increase in the next years due to the expected ageing of the population. Indeed, people aged 65 and over have higher prevalence of pathological tremor (about 3.9% compared with a 2% of the total population). Moreover prevalence increases with age (reaching up to 21% prevalence among the oldest group (95 and over) and faster tremor progression is observed. Therefore, it is estimated that by 2030 there will be a huge increase in the number of European people over 40 suffering from essential tremor, which are projected to grow from current 4.25M to 6.1M by 2030. Therefore, if effective solutions are not delivered, we can expect that there will still be more than 3.6M people by 2030 for whom essential tremor will be very debilitating and significantly impact on their quality of life. These social changes will result in a significant economical impact for the European Public Health systems, but also offer an opportunity for the SMEs of the TREM-END project. To assess the potential impact, the Consortium of the TREM-END project has firstly assessed the target selling price of the final device. The device is composed by two main components: the damping actuator (which embeds the damping system that will be developed within this project) and the orthotic substrate (composed by the thermoplastics supports and other minor interconnection parts, which will be also developed within the project according to the specifications of the final actuator).We have estimated a possible target price of the final device basing on the following expertise:• Cultraro: basing on the previewed specifications of the final damper and on Cultraro’s know-how on damping technology, we have been able to estimate material and production costs of the final damper (approx. 168€). Final selling price has then be estimated at 336€• EMO: thanks to its expertise in manufacturing and assembly of orthotics products, it has been possible to estimate material and production costs of the supports, as well as the costs of integration of the final device. As Cultraro will sell the damper to EMO at about 336€, the total cost of the final device for EMO will be 426€.• OKO: this company has a wide range of channels and partners for distribution of orthotics and orthopedic products across Europe. Therefore, through their expertise in this market sector it could provide estimates about final prices and gross added benefits to production costs of EMO. As EMO will also implement its own distribution net as a route to market, they will sell the orthosis at a final price of 681€, whereas will retail it to OKO at 571€ (33% gross profit added to orthosis cost of 426€). The final selling price for OKO will then be about 685€ (20% gross profit added to 571€). Therefore, as the selling price will be 681 for EMO and 685 for OKO, we will conservatively assume a final selling price of 680€.The estimated final price is realistic; for example, the Viscous Beam orthosis’ market price was estimated at 500$ in 1998 (approximately 550€ currently). Another comparison can be made with technologically similar orthotic products currently available on the market: as an example, an orthotic knee brace costs approximately 500-600€. Basing on the final selling price (680€) and the potential target users (2.2M people), the total expected potential market for the TREM-END orthosis will be about 1.5Bn €.Wider benefits at the European levelThe TREM-END project has been conceived with the aim of improving the competiveness of the involved SMEs by developing an innovative product. Additionally, this project addresses an important social problem that, as previously said, affects about 4.25M people of the European Union. Basing on the previous figures, we roughly estimate that there are over 2M people suffering from essential tremor that receive medical treatment every year; besides, we estimate that 4000 total surgery are carried out yearly, and approximately 980 are DBS surgeries whereas 3020 are Thalamotomy surgeries. Therefore, about 1.86Bn € are spent yearly by the Public Health System to provide treatment to this collective, as in most of EU countries medications are covered by social health insurances due to their high costs. The estimate do not take into account hospitalization costs, costs for revision surgery (e.g. in DBS to change batteries, DBS device failure, etc.) and other indirect costs.In Europe, the reimbursement system for orthotic devices differs among EU countries, as it may be partial (e.g. Belgium, France, etc.) or full (e.g. The Netherlands, Sweden, etc.). In order to assess cost savings, we will conservatively assume that in all countries reimbursement for orthotic devices is at 100% (maximum expenditure for the Public Health Systems). Moreover, we will assume that 15% of potential final users will avoid medication and 2% will avoid surgery by using the TREM-END orthosis. With these figures, cost savings for the Public Health Systems can be estimated at 3.435K€.The number of new annual users according to previewed market penetration figures. Of these users, we assumed that 15% benefit from the orthosis by avoiding medication and a 2% by avoiding surgery. By assuming treatment costs, “Total Treatment Cost-Savings” for the Public Health Systems have been calculated. Next, “Total Orthosis Expenditure” by the Public Health Systems has been calculated assuming a 100% reimbursement model. “Total Savings” derive from the difference between “Total Treatment Cost-Savings” and “Total Orthosis Expenditure”. As it can be noticed, savings will be positive from the third year (PPr4) after market implementation, making conservative assumptions. This validates the cost-effectiveness of the TREM-END orthosis concept for tremor suppression. Moreover, the expected cost savings will allow the European Commission to recover the investment committed for this project at the end of the fourth year after market implementation (PPr5), when the Total Savings will be equal or greater than the requested funding (1.12M€).The need for a transnational approachSince the individual SME members of our consortium are not in a position to progress this technology alone or have sufficient access the wider industrial markets, we have assembled a robust consortium of knowledge leaders from across Europe. Our partners have the experience, skills, capability and infrastructure to both develop this technology and address the longer term considerations for its dissemination and exploitation across the European market. The breadth of technological expertise has required us to involve research organisations from across the EU in order to provide the required capabilities.Another important issue to consider is that the orthotic system objective of this project relies on rotary damping technology. There are few SMEs in Europe owning that know-how and expertise, because rotary damping systems are mainly produced in low labour contries like China. Therefore it has been necessary to find and select an SME (Cultraro) outside the Coordinator’s country (Spain), as there exist no SMEs in the national territory with that profile. Moreover, the need of achieving a huge international economic impact, has required the involvement of a distributor of orthotics products with a wide distribution network across Europe (OKO).Finally, the chance offered by this Call for Proposal for an International Cooperation can provide an added value to the quality of the final outcomes and to the impact of the project. Indeed, from a societal point of view, the burden of essential tremor is a European problem, so a European action will increase enormously the impact compared with the action of particular SMEs. Through the financial support and the possibilities provided by this Programme, the TREM-END project will therefore be provided with the necessary resources of technology, knowledge and skills that will allow achieving project’s objectives.Estimated time to MarketDefinitive prototypes of the damping system, the damper, the orthotic substrate and the final orthosis (obtained from integration of the damper and the orthotics substrate (supports) will be developed and validated during the project. TREM-END orthosis is expected to be released to market ONE year after the project finalization. Two parallel activities are previewed within this period:• Patenting process (from month 22 to month 29) will start three months before the end of the project. We will start consulting with specialized Agencies (budget costs have been scheduled for EMO and Cultraro under “OTHER-Subcontract”) to prepare all the necessary documentation for the patenting of the four main project results. We will therefore ensure that within eight months after the finalization of the project, all the project’s results will be patented or at least “patent-pending”.• Implementation activities (month 25 to month 36) will start immediately after the project finalization and will run in parallel to patenting process. We will undertake all the necessary steps for launching the product into the market: final set-up for up-scaling production, creation of a wider distribution network, product packaging and additional marketing campaigns, future clinical trials and costs related to regulations applying to TREM-END product. The investment previewed for these activities by participating SMEs has been estimated at 300 K€ (144K€ for EMO; 96K€ for Cultraro; and 60 for K€ for OKO).Economic benefits to SME PartnersOur current exploitation plan predicts opportunities over a 5-year period post implementation. Basing on figures previously, the total Consortium’s turnover expected within five years after implementation will reach over 24 M€, whereas Consortium benefits will be about 7.5M€. EMO, after investing €840K in the project (Pr1+Pr2+PPr1), expects about €3.6M in economical benefits in six years post-project. Cultraro, after investing €580K in the project, expects about €2.4M in economical benefits in six years post-project. OKO after investing €300K in the project, expects about €1.6M in economical benefits in six years post-project.Basing on these figures and taking into account investments carried out during years Pr1, Pr2 and PPr1, we have also estimated the ROA (Return On Assets), the NPV (Net Present Value) at 7% and the IRR (Internal Rate of Return) for the single SMEs and for the whole Consortium during first 6 years post-project. First, the ROA is over 79% for all SMEs partners. The NPV is €1.7M for EMO, €1.1M for Cultraro and €0.83M for OKO. The IRR is about 43% or higher for all SME partners. All SMEs partner will recover their investment within three years after implementation because RTD activities in the project will be fully funded. For the whole project, ROA is 74%, whereas NPV is €3.6M and IRR is 46%. The whole project investment will be recovered within 3 years after the end of the project.Additional Benefits for the SMEsWe can distinguish into two types of long-term benefits for the SMEs participating in the project. On one hand, it is expected a short/mid-term impact in the competitiveness of the SME partners due to different factors depending on the company:• In the case of EMO, this project will allow extending their product’s portfolio: the launch in the market of a new product to solve a huge health problem to the users will therefore increase the perceived value of the company in the final market. This also applies to OKO, as it will also extend its product portfolio among its distribution network.• For Cultraro, this project will allow extending their damping applications to the medical sector (product differentiation), which will increase not only their annual turnover, but will also allow the alliance with companies addressed to large markets (medical devices). Consequently, Cultraro will increase the competitiveness and the perceived value of the company on the market.On the other hand, there are the mid/long term financial impacts derived from the SME individual results into other markets that have not been considered in the short term financial benefits for the SMEs. However, these potential exploitations will require further research and it is previewed that they will not be exploitable before the 4-5th year after the end of the project. However, the possible envisaged applications are the following ones:• EMO: possibility of developing further orthotic devices for tremor suppression in other joints different from wrist. • OKO: the commercial relationship that will be established with EMO for distributing the TREM-END orthosis will allow further commercial agreements for the distribution of other products in market areas not covered by EMO. Moreover, basing to this relationships, OKO will also benefit as a distributor of further orthotic devices for tremor suppression at other human joints different from wrist.• Cultraro: possibility of implementing the damping system concept (based on non Newtonian fluids) developed within the project to improve their current product portfolio with an added value embedded damping technology. Applications to other mechanical fields where damping capabilities are required are also previewed. However, further investigation will be required in this field.Dissemination activitiesA specific Work Package (WP6) has been defined to coordinate and organize the dissemination activities. The WP leader will be also responsible for the results dissemination, with the support of the Steering Committee. Only non confidential results will be disseminated. The particular strategies for dissemination of each partner result will be discussed during the project with the beneficed partner. Dissemination will cover three main aspects: Commercial dissemination will be carried out by EMO and OKO by participating at the most important orthotics and orthopedics trade fairs, among others ORPROTEC, REHACARE and REHA-TECHNIC. These SMEs will also use their own channels of information and advertising to promote the products and the achievements of the project. Cultraro will be in charge of dissemination regarding the new damping system and the damper that will be developed within the project (R1 and R2). Mass media dissemination will be carried out by all the partners using their respective means. It will cover press notes for mass media (journal, radio, TV), sectorial magazines and own magazines (i.e. Revista de Biomecánica edited by IBV). As well, the Project Web Site will serve for dissemination purposes. Scientific/technological dissemination will be carried out by RTDs (ISRI and IBV) through specialized international journals and conferences. The agreement of the SMEs beneficiaries is needed to allow the RTDs to publish the results of their research related to the project. Among the international conferences of interest there are: ICORR, AAATE, ISEK and the World Conference on Biomecanics (WCB). The journals of interest where the results can be published are: Technology and Disability (official journal of AAATE), Journal of Biomechanics, IEEE Transactions on Neural Systems and Rehabilitation Engineering, Journal of Neuroengineering and Rehabilitation and Movement Disorders.In the first half of the project, dissemination will remain limited to the distribution of publishable abstracts, as contractually required for EU RTD projects, to not endanger the industrial interests of the partners. During the second half of the project, the RTD Performers will provide support in the preparation of articles about the TREM-END orthosis to be published in scientific magazines and/or presented to international congress on orthotic/orthopedic products. Towards the end of the project, the dissemination activity will be coordinated within a marketing strategy. All provisions regarding Dissemination rules and duties will be gathered in the PUDK (Deliverables 6.3 and 6.6). The research leading to these results has received funding from the European Union's Seventh Framework Programme managed by REA-Research Executive Agency ([FP7/2007-2013] [FP7/2007-2011]) under grant agreement n° 262127.Exploitation resultsThe Exploitation Agreement (part of the PUDK) will gather all the provisions for the regulation of exclusive use and distribution rights and will specify all geographical and sectoral delimitations that will apply to these rights. The PUDK will also include productivity indicators and mid-term targets for each of the SME partners during exploitation stage (beyond the project life), these targets will be drafted by month 9 (Deliverable 6.2) and signed by all partners before month 24 (Deliverable 6.3). After the finalization of the project, PUDK rules for the use of the TREM-END foreground will be revisited by the exploitation committee (formed by the SME partners and any eventual new business partner) every two years. At these revisions, the exploitation committee will assess each business partner performance indicators against targets in order to decide the necessity of involving complementary business partners or of reallocating use rights to attain expected impacts and profitability (e.g. to increase component manufacturing capabilities or to broaden the distribution scope). New business partners will obtain the manufacturing, use and distribution rights through the payment of royalties or to the acquisition of licenses. The type and prices of royalties/licenses will be only negotiated by the owner of the IPR of the intended result.According IPR distribution stated, each SME partner will be the exclusive supplier of the SME partner directly beyond in the supply chain for the direct exploitation of the results after the project. In addition, each SME partner will have the exclusivity of exploiting the results in its own industrial sector (i.e. orthotic applications for EMO and all the other mechanical applications for Cultraro) or in different geographical areas (i.e. OKO distribution exclusiveness in France, Benelux, Finland, Norway, and Denmark).Exploitation of the TREM-END orthosis across the EU will be assured through the complementary combination of EMO distribution network and OKO (which at present reach 22 European countries plus 20 more countries around the world). EMO will target to reach in the mid-term, at least, Spain, Portugal, Poland, Sweden, Czech Republic and Romania through its own distribution network. In order to achieve the impact, EMO will concede the exclusivity of the distribution of TREM-END orthosis developed in France, Benelux, Finland, Norway, and Denmark to OKO. EMO and OKO have already come to this commercial agreement (exclusive distribution rights in different geographical areas) which will provide benefits for both companies with no overlaps. Beyond the project, further distribution partners may join EMO and OKO to enlarge the initial market scope and their profit. These new commercial agreements will be prior agreed by the Exploitation Committee.Each SME will elaborate its own ‘Individual Business Plan’ defining: (i) how the project results will be integrated into their own business activity, (ii) the required post-project investments, (iii) marketing strategy and (iv) mid-term market objectives and performance indicators (WP6; Deliverable 6.5; month 24).List of Websites:htpp://trem-end.ibv.org/
