Review Article Assessing Effectiveness and Costs in Robot-Mediated Lower Limbs Rehabilitation: A Meta-Analysis and State of the Art

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1 Journal of Healtcare Engineering Volume 2018, Article ID , 9 pages ttps://doi.org/ /2018/ Review Article Assessing Effectiveness and Costs in Robot-Mediated Lower Limbs Reabilitation: A Meta-Analysis and State of te Art Giorgio Carpino, 1 Alessandra Pezzola, 1 Micele Urbano, 2 and Eugenio Guglielmelli 1 1 Laboratory of Biomedical Robotics and Biomicrosystems, Università Campus Bio-Medico di Roma, Rome, Italy 2 Polyclinic General Direction, Università Campus Bio-Medico di Roma, Rome, Italy Correspondence sould be addressed to Giorgio Carpino; g.carpino@unicampus.it Received 12 February 2018; Revised 6 April 2018; Accepted 22 April 2018; Publised 4 June 2018 Academic Editor: Carlo Ferraresi Copyrigt 2018 Giorgio Carpino et al. Tis is an open access article distributed under te Creative Commons Attribution License, wic permits unrestricted use, distribution, and reproduction in any medium, provided te original work is properly cited. Robots were introduced in reabilitation in te 90s to meet different needs, tat is, reducing te pysical effort of terapists. Tis work consists of a meta-analysis of robot-mediated lower limbs reabilitation for stroke-affected patients; it aims at evaluating te effectiveness of te robotic approac troug te use of wearable robots or operational macines wit respect to te conventional approac (i.e., manual reabilitation terapy). Te primary assessed outcome is te patient s ability to recover walking independence, wereas te secondary outcome is te average walking speed. Te terapy acceptability and te treatment costs are also assessed. Te assessment sows tat te robot-mediated terapy is more effective tan te conventional one in reacing te primary outcome. As for te secondary outcome, tere is no significant difference between te robotic (wearable robots or operational macines) and te conventional approac. Reabilitation using wearable robots as a greater acceptability tan te conventional one. Tis does not apply to operational macines. Te cost of robotic treatment wit wearable robots ranges from double to triple te cost of te conventional approac. On te contrary, reabilitation using operational macines costs te same as te conventional treatment. Robotic reabilitation based on operational macines is te most cost-effective approac. 1.Introduction Te introduction of robots in reabilitation terapy dates back to te 1990s [1]. Since ten, te reabilitation terapy as been led by te following factors:(i) modern medicine is based on objective assessments and quantitative bencmarking of te impact of different terapeutic approaces; (ii) conventional reabilitation terapy (i.e., manual reabilitation terapy) is an intense, time-consuming activity, wic requires ig pysical effort for ealt workers; (iii) recent studies on neuroplasticity related to functional recovery in patients wit brain injuries ave igligted tat patients benefit from activity-dependent reabilitation terapies. Tese factors usually require te execution of repetitive exercises, aimed at a well-defined goal. Te patient as to ave an active role during te reabilitation session in order to stimulate te wole system of sensorimotor coordination, including te stages of imagination and planning of te motor task. Terefore, tere are unmet or not completely met needs in te conventional approac to te motor reabilitation suc as availability of measurable outcomes, repeatability of te reabilitation tasks, and active patient engagement. Robotic solutions for assisted terapy meet all tese needs [2, 3]. Reabilitation robotics is a new tecnological branc related to te application of robot tecnology in medical fields. Nowadays, reabilitation robots are a key enabling tecnologies to elp people wo suffer limb movement disorder to restore te normal pysiological muscular activity wit te possibility of gain-measurable outcomes. Robot-mediated reabilitation aims at developing new solutions for assisted terapy, tus allowing an objective functional assessment of patients. Due to te advantages of teir accuracy and reliability, reabilitation robots can provide an effective way to improve te outcome of stroke or postsurgical reabilitation. Robotic tecnology offers

2 2 JournalofHealtcareEngineering (i) accuracy, precision, and simple tools for te modelling of te uman beaviour; (ii) repeatable and continuous movements of te uman districts to reabilitate; and (iii) active engagement of te patients during te reabilitation tasks, tat is, troug virtual reality-based exercises. Robotic devices for reabilitation fall into two broad categories (i.e., te ones considered in tis paper) based on te relationsip between te movements of te uman body and tose of te macine [4]: (i) macines: Te pysical interface between te robot and uman body is in a defined part of te body, usually te effectors. For tese macines, te trajectories of te robot end-effector and te uman end-effector in te operational space are pysically coupled. In te joint space, instead, te trajectories of te robot joints and te uman joints can be significantly different, so tat, kinematic scemes can also be selected based on only te specific requirements of te target application scenario. (ii) robots: In tese macines, a large portion of te uman body(typically te wole affected limb) is in continuous pysical contact wit te robot. In most cases, a biomimetic exoskeleton kinematic structure is selected. Terefore, not only te trajectories of te robot end-effector and te uman end-effector are te same in te operational space but also te trajectories of te robot joints approximate tose of te uman joints in te joint space. Tese systems require advanced biomecatronic design approaces in order to mimic uman-like joints motion, wile minimizing invasiveness for te patient in terms of weigt, dimensions, and so on. To overcome tese callenging problems, nonbiomimetic wearable robots are also currently under investigation in a few pilot researc projects recently launced in Europe and te U.S.[5, 6]. robots for walking reabilitation can be divided in turn into nonportable and portable systems, depending on weter tey are fixed to a specific environment or not. Portable systems are autonomous wile nonportable systems require a source of energy. Reabilitation wearable robots can also be classified as robots for reabilitation on treadmill and robots for overground walking reabilitation [7, 8]. Lokomat (Hocoma AG, Volketswil, Switzerland), trade namefortedgo(drivengaitortosis),isoneoftemost widely used wearable robots. It is a nonportable robot for treadmill reabilitation, wit an antropomorpic nonredundant structure. It assists and guides te ip and knee movements in te sagittal plane, wile te ankle joint is not actuated[9]. LOPES(lower-extremity powered exoskeleton) is anoter example of nonportable robot. It assists flexion/ extension and abduction/adduction of te ip and flexion/ extension of te knee [10]. ALEX (active leg exoskeleton) is a wearable robot for treadmill reabilitation wit two actuated degrees of freedom, wic allow movement in te sagittal plane of te ip and knee joints[11]. AutoAmbulator and Walkbot are nonportable robotic systems wit a mecanical structure very similar to Lokomat [12, 13]. ReWalk(ReWalk Robotics, Marlboroug, US) is a mobile exoskeleton tat allows overground reabilitation. Te battery and te controllers are inside te backpack tat te patient wears on is soulders. It is primarily used for SCI patients, and it must be used in conjunction wit crutces [14]. Gait Trainer GT I(Rea-Stim, Berlin, Germany) is one of te most widespread operational macines for walking reabilitation, and it consists of two footplates connected wit te patient s feet mimicking te walking cycle [15]. Gait Master 4 is anoter operational macine based on te movement of two footplates moved by a connecting rodcrank system. Te footplates allow te movement of te uman effector back and fort (to simulate te walk) or up and down (up/down te stairs) [16]. In tis paper, te autors provide a cost-effectiveness assessment to compare, in terms of efficiency, conventional reabilitation terapies to wearable robot-/operational macine-mediated reabilitation for te treatment of stroke-affected patients. Te present work aims at assessing te effectiveness of te two terapeutic approaces and evaluating te costs for bot types of procedure. 2.Materials and Metods 2.1. Assessment of Effectiveness. Te autors ave carried out areviewoftearticlesattestateofteart,wiccompares te effectiveness of robot-mediated and conventional reabilitation in stroke-affected patients. Te analysis is based on average recovery of patients treated wit te two approaces. Te study includes all te articles in te Cocrane review[17] and more recent studies[13, 18 21]. Te studies includedintisreviewfocusonpatientswosufferedafirst stroke, wo are over 18 years old (wit an average age ranging between 48 and 71 years old), wo ave sufficient cognitive and communication skills tat allow a correct understanding of te reabilitation session, and wo do not suffer cardiac, psycological, and ortopaedic contraindications. Te autors ave included studies on patients in acute and subacute pases(time elapsed since te ictal event not exceeding tree monts), on cronic patients, and on patients wit different levels of disability. Te patient groups range from patients wo are able to walk independently even before te beginning of te reabilitation terapy to patients wo are completely dependent to walk. All clinical trials are based on te random division of patients into two groups: group A and group B. (i) Group A: patients in tis group underwent a reabilitation programme consisting of several sessions of robot-mediated terapy and some additional manual terapy session. (ii) Group B: patients in tis group underwent conventional terapy only. Depending on te particular study, macines used for te robot-mediated reabilitation of patients in te group A are wearable robots(lokomat in most of te articles, but also AutoAmbulator, Anklebot, and Walkbot in one study eac) or operational macines (Gait Trainer I in all cases except

3 JournalofHealtcareEngineering 3 one were Gate Master 4 is used). In bot cases, training witabws(bodyweigtsupport)iscarriedout;a30 40% of body weigt support during te first reabilitation session is applied. Te body weigt support is progressively reduced as te patient recovered is/er locomotor ability. At te end of te reabilitation process, te primary outcome is te ability of te patients to recover walking independence. Te secondary outcome is te average walking speed. Te acceptability of te terapy is assessed taking into account te number of dropouts, tat is to say, te number of patients wo do not complete te entire reabilitation process. Te autors ave applied te same statistical metods as tose used in te Cocrane review[17], altoug not explicitly described ere, but suggested by te omonymous statistical group in te Cocrane Handbook for Systematic Reviews of Interventions [22]. Te odds ratio(or) is calculated for eac article. It measures te number of patients wo recovered walking independence at te end of te robotic treatment compared to te conventional one, as well as to quantify te number of dropouts. Te OR is calculated as follows: OR i a i d i b i c i, (1) were a i istenumberofpatientsingroupaworecovered independence in walk at te end of te planned reabilitation process, b i is te number of patients in group A wodidnotrecoverindependenceinwalk, c i istenumber of patients in group B wo recovered independence in walk, and d i is te number of patients in group B wo did not recoverindependenceinwalk.similarly, a i, b i, c i,and d i can beusedtomeasuretenumberofpatientswocompletedor not te entire reabilitation process. Te Mantel Haenzsel (MH) random-effects metod is used for meta-analysis and to calculate te Overall OR, wic takes into account te results of eac article: OR MH wmh i w MH i OR i, (2) wit w MH i b i c i /n i, were n i a i + b i + c i + d i. If no participant or if every participant in te study acieved te ability to walk independently, te OR of te it article is considered not estimable, and it is, tus, not included in te meta-analysis. Wen tis situation just occurs only in one of te two groups (A or B), a modified formula is used. OR i is calculated by adding a factor equal to 0.5 to eac element in (1). Te confidence interval (CI) is calculated taking into account te overall standard error SE(lnOR MH ), according to te following formula: 95% CI e lnor MH 1,96 SE( lnor MH ), e lnor MH +1,96 SE lnor ( MH ), (3) wit SE(lnOR MH ) (1/2)((E/R 2 )+(F+G/R S) +(H/S 2 )), were R a i d i /n i, S b i c i /n i, E (a i + d i ) a i d i /n 2 i, F (a i + d i ) b i c i /n 2 i, G (b i + c i ) a i d i /n 2 i, and H (b i + c i ) b i c i /n 2 i. If 95% CI includes value 1 (no effect), te result described by te corresponding OR does not demonstrate a clear effectiveness, and it is not considered significant. Te mean difference (MD) is used to calculate te secondary outcome: (MD v ) i RT v i CT v i (m/s), (4) were RT v i is te average speed tat patients reaced at te endofteroboticterapy,and CT v i is te average speed tat patients reaced at te end of te conventional terapy. Te inverse variance(iv) random-effects metod is used to calculate te Overall MD: (MD v ) IV w i (MD v ) i w i (m/s), (5) wit w i 1/SE(MD v ) 2 i, were SE(MD v ) 2 i is te variance of te it article. Te CI is calculated taking into account te overall standard error SE(MD v ) IV, according to te following formula: 95% 2CI (MD v ) IV 1.96 SE(MD v ) IV ; (MD v ) IV SE(MD (6) v ) IV, wit SE(MD v ) IV 1/ w i. If 95% CI includes te value 0 (no effect), te result described by te corresponding MD does not demonstrate a clear effectiveness, and it is not considered significant. Establising te abovementioned statistical metods, te autors verified to be able to exactly reproduce te same results reported in te Cocrane review [17] (wit a difference of maximum 0.02). Terefore, tey carried out te calculations again, considering also te 5 more recent studies [13, 18 21], tat perfectly fit in terms of inclusion criteria for tepatientsandtetypeoftrialswittepapersincludedin te Cocrane review Costs Analysis. Altoug in most of te studies patients were ospitalised for reabilitation terapy, te autors take into account only te costs of te reabilitation terapy, wereas ospitalisation costs are not considered, as tey are effectively te same in te robotic and conventional approaces. Costs of medications, meals, and electricity are identical because te duration of te reabilitation process, inallstudiesincludedintisreview,istesameforpatients of group A and B. Te same applies to ealt cost reimbursements from te Lazio Region, wic are te same in Italy for te conventional- and robot-mediated terapies [23]: (i) C terapist ( /), ourly cost of a single pysioterapist (ii) n terapists, average number of terapists per session per patient (iii) t session (min), average session duration (iv) n sessions, average number of sessions for te entire reabilitation process for patients mentioned in te articles.

4 4 JournalofHealtcareEngineering Te ourly cost of conventional terapy (C Conventional ), cost per session (C Conventional session ), and cost of te entire reabilitation process (C Conventional ) are calculated. Te cost estimate of te robot-mediated treatment takes into account te abovementioned parameters and also te cost to purcase te robot (C Robot purcase ( )), te number of years to amortise te robot (y amortization (years)), and te annual routine maintenance cost (C maintenance y ( /year)). Teoursofpotentialuseofterobotinaealtfacility are estimated to calculate te ourly cost of te robot (and te cost per session). Pysioterapists working sifts are takenintoaccounttogetanideaofowmanyoursperday te robot can be used for reabilitation sessions. Two possible working sifts were identified in collaboration wit te Polyclinic General Direction of Campus Bio-medico (Rome, Italy), amounting to a of 36 weekly working ours. Te cost of te robotic terapy is, terefore, calculated for bot sifts: (i) 1st case : robot used 7.12 ours per day, 5 days a week. Tis is te amount of weekly working ours of a single terapist. (ii) 2nd case : robot used 12 ours per day, 6 days a week. Tis is te amount of weekly working ours of two terapists, one working in te morning and te oter in te afternoon. Tis allows to calculate te ourly cost (C Robot ), te cost persession(c Robot session ),andtecostofteentirereabilitation process (C Robot ) for te robotic terapy. Te cost estimate for te entire training process of te two groups (A and B) takes into account, for bot approaces (robotic and conventional), te additional cost of conventional terapy in te clinical trials as extra training for patients in bot groups: C patient (Robot or Conventional) C + C additional. (7) Tis means tat (7) is calculated taking into account te costoftespecificreabilitationprocess(c Robot for group A and C Conventional for group B), plus te additional cost of conventional terapy extra sessions Cost-Effectiveness Analysis. Te ICER(incremental costeffectiveness ratio) is calculated to compare te efficiency of te two approaces (conventional versus robotic) and to determine wic one is most cost-effective: ICER C A C B E A E B, (8) were C A and C B are te cost of te entire reabilitation process for robot-mediated terapy and conventional terapy, respectively, wereas E A and E B measure te effectiveness of eac terapy in terms of primary outcome, tatistosay,teoverallorforwalkingindependence,orin terms of secondary outcome, te Overall MD of walking speed. Wen calculating te ICER, it is important to distinguis weter te difference in effectiveness is expressed in terms oforormd.wentedifferenceineffectiveness(e A E B ) is expressed in terms of Overall OR, C A and C B are calculated by multiplying te cost of te entire reabilitation process per patient (C patient ) per te average number of treated patients. Wen te difference in effectiveness (E A E B ) is expressed in terms of Overall MD, C A and C B costs are equal to C patient. In bot cases, robot-mediated terapy is more effective tan te conventional terapy wen te ICER value is low. A low value at te ICER ratio numerator indicates a small difference in cost between te two approaces, wereas a ig value at te denominator marks a ig OR or MD, wic means tat te robotic terapy is muc more effective tan te conventional terapy. Te more te OR is>1 or MD is>0, te more te robot-mediated terapy is effective compared to te conventional one. Terefore, te ICER is te difference in terms ofcostfortetwoapproaces,weigtedbytedifferenceof effectiveness. 3.Results and Discussion 3.1. Effectiveness. A number of 26 trials are included wit a of 1064 patients, all of tem affected by a stroke for te first time. 60% of te patients are men and 40% are women, 70% are affected by iscemic stroke and 30% by aemorragic stroke, and 50% ave a left emiparesis and 50% a rigt emiparesis. Te number of sessions and teir duration and frequency are te same in group A and group B. Te autors ave selected te appropriate number of articles to assess te primary and secondary outcomes, as well as te terapy acceptability in tree different cases: (1) Robot-mediated terapy for group A based on te use of bot wearable robots and operational macines. (2) Robot-mediated terapy for group A based on te use of wearable robots, (3) Robot-mediated terapy for group A based on te use of operational macines. In all te tree cases, te robot-mediated terapy is more effective tan te conventional one to recover te patient walking independence (Overall OR > 1) wit statistically significant results (p value<0.05 and 95% CI not including value1),assowninfigure1.teorisequalto2.38inte first case (p value<01, 95% CI between 1.68 and 3.39), 2.28 in te second case (p value 38, CI between 1.31 and 4.00), and 2.45 in te tird case (p value 01, 95% CI between 1.56 and 3.85). As for te average walking speed acieved at te end of te reabilitation process, te robotic terapy is sligtly more effective tan te conventional one (Overall MD is 0.04m/s, p value 26, 95% CI between 0.01 and 0.06). macines, in particular, are more effective tan wearable robots, as sown in Figure 2. macines MD is 0.14m/s (p value<01, 95% CI between 0.09 and 0.19). robots ave a null MD, wic means tat wearable robots are as effective as conventional terapy.

5 JournalofHealtcareEngineering 5 Overall OR (walking independence) Overall MD (m/s) (walking speed) and operational 0.14 Figure2:OverallMD(and95%CI)forwalkingspeedintetree different cases based on te type of robot used for te reabilitation of patients in group A. Overall OR (treatment dropout) and operational 0.58 and operational 0.39 Figure1:OverallOR(and95%CI)forindependenceinwalkinte tree different cases based on te type of robot used for te reabilitation of patients in group A Figure 3: Overall OR (and 95% CI) for dropouts in te tree different cases based on te type of robot used for te reabilitation of patients in group A. However, tis result is not statistically significant (p value 0.89, 95% CI between 0.02 and 0.03). Regarding te acceptability, te robotic terapy is more effective tan te conventional one wit OR equal to 0.58 (p value 0.01, 95% CI between 0.39 and 0.88), as sown in Figure 3. OR<1 indicates fewer dropouts. However, te results sow differences based on te type of robot used for te reabilitation of patients in group A. Te terapy based onteuseofwearable robotsismucmoreacceptabletan te conventional one (OR 0.39, p value 07, 95% CI between 0.23 and 0.67). Te terapy based on te use of operational macines as te same acceptability as te Overall OR (walking independence) Subacute pase and operational Cronic pase Figure 4: Overall OR (and 95% CI) for walking independence based on te type of robot and te condition of patients (cronic versus subacute pase). conventional one (OR 1.02). However, tis result is not statistically significant (p value 0.95, 95% CI between 0.53 and 1.99). Te autors distinguis between te results for te primary and secondary outcomes depending on patient conditions, tat is to say, patients in te subacute or cronic pase. Te use of different types of robots to recover te independence in walk produces different results, as sown in Figure 4. Te terapy based on teuse of wearable robots is more effective tan te conventional one for patients bot in te cronic (OR 2.35, p value 0.17, 95% CI between 0.68 and 8.07) and subacute pases (OR 2.27, p value 0.01, 95%CIbetween1.21and4.25).Teterapybasedonteuse of operational macines is extremely more effective tan te conventional one for patients in te subacute pase (OR 3.12, p<01,95%cibetween1.90and5.14),butit is less effective tan te conventional terapy for cronic patients. However, tis result is not statistically significant (OR 0.58, p value 0.40, 95% CI between 0.16 and 2.04). Wit regards to walking speed, results sow no big difference between patients in te subacute or cronic pases, as sown in Figure 5. Te terapy based on te use of operational is more effective tan te conventional one for bot patients in te subacute and cronic pases. For patients in te cronic pase, MD is equal to 0.14m/s (p value 0.01, 95% CI between 0.03 and 0.26). Similar results are obtained for patients in te subacute pase: MD is equalto0.14m/s(pvalue<01,95%cibetween0.09and 0.19). Te terapy based on te use of wearable robots is as effective as te conventional one for patients in te subacute pase (MD 0m/s), but te result is not statistically significant(pvalue 0.77,95%CIbetween 0.02and0.03)and less effective tan te conventional one for cronic patients (MD 0.02m/s), but te result is still not statistically significant (p value 0.68, 95% CI between 0.10 and 0.06) Costs. Similar to te effectiveness analysis, tree types of comparisons between training costs for te two groups (A

6 6 JournalofHealtcareEngineering Overall MD (m/s) (walking speed) Subacute pase and operational Cronic pase Figure5:OverallMD(and95%CI)forwalkingspeedbasedonte type of robot and te condition of patients(cronic versus subacute pase). and B) are carried out. Te first comparison is based on all te articles included in te review, irrespective of te type of robot used for te terapy(operational macine or wearable robot). Te oter two comparisons focus on two subcases: one based only on studies on wearable robots and te oter only on studies on operational macines. Te results are based on a 20 / cost per terapist (as per 2014 Collective Bargaining Agreement in Italy) and 5 years to amortise te robot, as per ig-tec medical equipment tax rate [24]. Te annual robot maintenance cost is calculated as 10% of te robot value. For wearable robots, te reference value is set to te Lokomat cost, tat is, 330,00. For operational macines, te reference value is set to te Gait Trainer GT I, tat is, 30,00. For te robotic terapy in general regardless of te type of robot te robot purcase cost is, tus, set equal to 225,00, wic is te average between te costs of Lokomat and Gait Trainer GT I weigted by te number of reference articles. Table 1 sows te parameters used to calculate costs and te relative results, wen comparing te conventional terapy to te robot-mediated one, in bot te cases described in section Cost Analysis. As it could be imagined, te robot-mediated terapy is more expensive and, terefore, less economically sustainable tan te conventional one. Te cost estimate sows very different results for te terapybasedonteuseofwearablerobotandteonebased on operational macines. Table2summarisesteourlycostandcost(forte full reabilitation of a patient) for conventional terapy, wearable robots terapy, and operational macines terapy. Te terapy wit wearable robots costs about tree times more tan te conventional one considering 12.7 ours of possible use of te robot for 5 days a week ( 1st case ). Te cost decreases and is about two times more tan te cost of te conventional terapy wen it is based on 12 ours of possibleuseofterobotfor6daysaweek( 2ndcase ).Te cost of te terapy wit operational macines, on te contrary, is te same as te cost of te conventional terapy Table 1: Costs analysis of robotic terapy versus conventional terapy: parameters and cost estimate results. Robotic 1st case 2nd case Conventional Parameters C terapist ( /) n terapists t session (min) n sessions C Robot purcase ( ) 225,00 225,00 y amortization (years) 5 5 C maintenance y ( /year) 22,50 22,50 Daily robot use (ours per day) Weekly robot use (days per week) 5 6 Results C terapy ( /) ( /session) C terapy session C patient ( ) 1, Table 2: Hourly cost and cost: comparison between conventional, wearable robots, and operational macines terapies. Conventional robot 1st case 2nd case robot 1st case 2nd case C terapy ( /) C patient ( ) , in te 1st case and even lower tan te cost of te conventional terapy in te 2nd case Cost-Effectiveness (ICER). ICER estimates are carried out for te tree cases described in section Effectiveness. For eac case, two different values of ICER are calculated te first is based on te cost estimate of te robotic terapy in te 1st case and te second in te 2nd case. Figure 6 sows ICER values regarding patients recovering walking independence. For te robot-mediated terapy in general, witout considering te type of robot, ICER is 4, in te 1st case and is lower in te 2nd case, 1, Taking into account, instead te type of robot, results are very different. Te wearable robots terapy asaigericer: 7,889.21inte 1stcase and 3, in te 2nd case. Te ICER for operational macines terapy is muc lower and amounts to in te 1st case. Increasing te number of ours of possible use of te robot ( 2nd case ), te ICER as a negative value ( ). Tis means tat te operational macines terapy is not only 2.45 times more effective tan te conventional one in te case of patients recovering independence in walk (as sown by te Overall OR), but also

7 JournalofHealtcareEngineering 7 ICER ( ) for walking independence ICER ( s/m patient) for walking speed 9,00 7,50 6,00 4,50 3,00 1,50 1,50 120,00 95,00 70,00 45,00 20,00 5,00 te terapy is even more economically sustainable, as it allows to save Figure 7 sows ICER values of patients recovering average walking speed. Te ICER of te operational macines terapy is ( /patient)/(m/s) in te 1st case. Tis means tat te robotic terapy costs approximately 60 more tan te conventional one per patient per meter per second of recovered walking speed. In te 2nd case, te ICER is negative ( /patient/m/s). Results are very different for wearable robots: te ICER fortemisdivergentbeingpresentazeroatdenominatorin (8) (Overall MD 0m/s bot in te 1st case and in te 2nd case ). 4.Conclusions 4, , , st case and operational Infinite 1st case and operational 1, , , nd case Figure 6: ICER values related to te independence in walk in te differentcasesbasedontetypeofrobotusedandon teoursof potential use of te robot. Infinite 2nd case Figure 7: ICER values related to te independence in walking in tedifferentcasesbasedontetypeofrobotusedandonteours of potential use of te robot. Divergent ICER, for grapic purposes, set equal to 100,00. Robot-mediated terapy as proven to be more effective tan conventional terapy in te treatment of strokeaffected patients. Overall OR results sow tat te robotic terapy enables a larger number of patients to recover independence in walk, compared to te conventional terapy. Tis applies to all analysed cases, being te terapy based on te use of wearable robots or operational macines and being te patients in a cronic or subacute pase. Tis is particularly interesting since te time tat patients in group Aspentforroboticterapyislesstantetimetatpatients in group B spent for conventional terapy. In te analysed studies, te duration of te reabilitation session and te number of sessions are te same for bot groups. However, for patients in group A, about alf of te session time is not spent training wit te robot but rater settingup te macine. In conventional terapy for patients in group B, te session is entirely dedicated to te reabilitation procedure. Te terapy based on te use of operational macines is te most effective treatment, wit te igest Overall OR. Tis may be due to limitations of wearable robots. For instance, in te case of exoskeletons wen te coupled joint-links are not perfectly aligned wit te uman joints, undesired ig forces are produced [25]. Tis makes te robot a danger to te patient, as well as an obstacle to is/er movement. Tis does not appen wit operational macines. macines are more effective for patients in te subacute pase, wereas wearable robots are more effective for patients in te cronic pase. Tese results, owever, are not statistically significant and require furter study in te future. In terms of secondary outcome, robot-mediated terapy as te same effectiveness as conventional terapy. To sum up, robotic terapy is particularly effective in te treatment of critical patients, wo are unable to walk independently before starting te reabilitation process. For critical patients, te most important goal is to recover te walking autonomy, wic is more easily acieved troug robotic terapy. For patients wo are already able to walk autonomously, te main goal is to recover walking speed; tus, te robotic terapy is not particularly convenient for tem. Furter studies are needed to assess te effectiveness of robot-mediated terapy wit wearable robots to acieve te secondary outcome. Current results on tis aspect are still not statistically significant. As for terapy acceptability, patients wo underwent robotic terapy wit wearable robots ave te lowest number of dropouts. Tis result is rater unexpected, as te autors tougt tat robot-mediated terapy would not be well accepted. A possible explanation may lie in te fact tat te terapist is always present during te sessions, supervising te patient, prompting is/er active participation, and making im/er feel safe. In addition to tis, te robot reduces te pysical effort required to te patient and relieves is/er fatigue, especially wen e/se is in difficulty. Anoter element to take into consideration is tat te wearable robot allows patients to walk as of te very first session. Tis could ave a positive impact on te patient s psycological response, by increasing is/er self-confidence and motivation to keep on training. As for te economic point of view, robotic terapy based on te use of wearable robots as proven to be very expensive. Costs decrease as te ours of possible use of te robot increase. Te gap between te cost of robotic and conventional terapies is considerable. Robotic terapy based on te use of operational macines is te most

8 8 JournalofHealtcareEngineering economically sustainable metod due to te low purcasingcost.itmustbesaid,owever,tattecostofrobotmediated and conventional terapies is estimated based on te assumption tat training time is te same for bot terapies. Te fact tat te duration of te reabilitation terapy is te same for patients in bot groups A and B is based on wat is reported in te articles included in tis study. Tis, in addition to te lack of information on posttrainingpatientsqualityoflife,meanstatteautors can evaluate only some of te direct medical costs of te terapy. It is not possible to make a comparison between te two reabilitation approaces in terms of nonmedical directcosts(i.e.,socialservices,omecare,transportation, etc.)norindirectcosts(i.e.,workingdayslostbytepatient due to treatment and ealt care, working days lost in termsoflowerproductivityofworkingpatients,etc.).also, te fact tat patients of bot groups (A and B) underwent a programme wit a similar structure does not allow to analyseoterpossiblecostdifferencesrelated,forinstance, todaysofospitalisationforpatientslocomotionrecovery. Te autors, tus, igly recommend organizing clinical trials differently. Rater tan aving all patients undergoing a reabilitation terapy, wic as te same duration, it migt be useful to set targets (sufficient values of effectiveness) and assess patients recovery time against suc targets. Tis would allow for a more realistic assessment of te cost of robot-mediated and conventional terapies, wic takes into account rest days for patients to acieve targets and te oter aspects mentioned above. Future clinical trials sould also consider different metods for a proper assessment of nonmedical direct and indirect costs. Taking into account bot economic aspect and effectiveness, te cost difference between robotic terapy and conventional terapy is reduced. ICER results for te primary outcome sow tat te terapy based on wearable robots is more effective tan te conventional one but also more expensive.tis trend is even moreevident if weconsidericer results for te secondary outcome. In tis case, te ICER is divergent. Tis means tat an infinite amount of resources would ave to be spent to increase te patient s walking speed. In oter words, robot-mediated terapy based on te use of wearable robots as a cost for benefit equal to 0. It is infinitely less efficient tan conventional terapy. On te contrary, reabilitation terapy based on operational macines is te most cost-effective one, as ICER values are very low and in some cases, even negative. In conclusion, te study sows tat robotic terapy basedonteuseofoperationalmacinesistemostefficient strategy. It is muc more effective tan te conventional one, wit statistically significant results, bot in terms of patients recovery of walking ability and walking speed. It is also muc more economically sustainable tan robotic terapy based on te use of wearable robots, as its cost is similar, if not lower, tan te cost of conventional terapy. However, te terapy wic as te igest patients acceptability is te one based on te use of wearable robots. Te investigated topic, and in general te assessment studies on medical devices, is relatively new wit respect to te studies on drugs, te scientific evidence is sparse, and te attempts to collect information are callenging but te need of te assessment for medical device is crucial for supporting te decision-making process [26]. Conflicts of Interest Te autors declare tat tere are no conflicts of interest regarding te publication of tis paper. References [1] W. S. Harwin, J. L. Patton, and V. Reggie Edgerton, Callenges and opportunities for robot-mediated neuroreabilitation, Proceedings of te IEEE, vol. 94, no. 9, pp , [2] D. P. Ferris, G. S. Sawicki, and A. Domingo, Powered lower limb ortoses for gait reabilitation, Topics in Spinal Cord Injury Reabilitation, vol. 11, no. 2, pp , [3] M. Fairley, I, Robot: Robotic Tecnology Adds a New Dimension to Ortotics, Western Media LLC, Nortglenn, CO, USA, [4] E. Guglielmelli, M. J. Jonson, and T. Sibata, Guest editorial, special issue on reabilitation robotics, IEEE Transactions on Robotics, vol. 25, no. 3, pp , [5] D.Accoto,F.Sergi,N.L.Tagliamonte,G.Carpino,A.Sudano, and E. Guglielmelli, Robomorpism: a nonantropomorpic wearable robot, IEEE Robotics and Automation Magazine, vol. 21, no. 4, pp , [6] N. L. Tagliamonte, F. Sergi, G. Carpino, D. Accoto, and E. Guglielmelli, Human-robot interaction tests on a novel robot for gait assistance, in Proceedings of te IEEE International Conference on Reabilitation Robotics ICORR, pp. 1 6, Seattle, WA, USA, June [7] S. Sargsyan, V. Arakelian, and S. Briot, Robotic reabilitation devices of uman extremities: design concepts and functional particularities, in Proceedings of te 11t Biennial Conference on Engineering Systems Design and Analysis ESDA, pp. 1 10, Nantes, France, July [8] S. Hussain, S. Q. Xie, and G. Liu, Robot assisted treadmill training: mecanisms and training strategies, Medical Engineering and Pysics, vol. 33, no. 5, pp , [9] G. Colombo, Te lokomat: a driven ambulatory ortosis, Medicine Ortopaedics Tecnology, vol. 6, pp , [10] J. Veneman, R. Kruidof, E. Hekman, R. Ekkelenkamp, E. V. Asseldonk, and H. van der Kooij, Design and evaluation of te LOPES exoskeleton robot for interactive gait reabilitation, IEEE Transaction on Neural Systems and Reabilitation Engineering, vol. 15, no. 3, pp , [11] S.Banala,S.H.Kim,S.Agrawal,andJ.Scolz, Robotassisted gait training wit active leg exoskeleton (ALEX), IEEE Transaction on Neural Systems and Reabilitation Engineering, vol. 17, no. 1, pp. 2 8, [12] J. A. Galvez and D. J. Reinkensmeyer, Robotics for gait training after spinal cord injury, Topics in Spinal Cord Injury Reabilitation, vol. 11, no. 2, pp , [13] S. Y. Kim, L. Yang, I. J. Park et al., Effects of Innovative WALKBOT robotic-assisted locomotor training on balance and gait recovery in emiparetic stroke: a prospective, randomized, experimenter blinded case control study wit a four-week follow-up, IEEE Transactions on Neural Systems and Reabilitation Engineering, vol. 23, no. 4, pp. 1 7, [14] A. Esquenazi, M. Talaty, A. Packel, and M. Saulino, Te ReWalk powered exoskeleton to restore ambulatory function to individuals wit toracic-level motor-complete spinal cord

9 JournalofHealtcareEngineering 9 injury, American Journal of Pysical Medicine and Reabilitation, vol. 91, no. 11, pp , [15] S. Hesse and D. Ulenbrock, A mecanized gait trainer for restoration of gait, Journal of Reabilitation Researc and Development, vol. 37, no. 6, pp , [16] N. Tanaka, H. Saitou, T. Takao et al., Effects of gait reabilitation wit a footpad-type locomotion interface in patients wit cronic post-stroke emiparesis: a pilot study, Clinical Reabilitation, vol. 26, no. 8, pp , [17] J. Merolz, B. Elsner, C. Werner, J. Kugler, and M. Pol, Electromecanical-assisted training for walking after stroke (review), Cocrane Database of Systematic Reviews, no. 7, pp , [18] M. P. M. van Nunen, K. H. L. Gerrits, M. Konijnenbelt, T.W.J.Janssen,andA.deHaan, Recoveryofwalkingability using a robotic device in subacute stroke patients: a randomized controlled study, Disability and Reabilitation: Assistive Tecnology, vol. 10, no. 2, pp , [19] L.W.Forrester,A.Roy,A.Krywonis,G.Kes,H.I.Krebs,and R. F. Macko, Modular ankle robotics training in early subacute stroke: a randomized controlled pilot study, Neuroreabilitation and Neural Repair, vol. 28, no. 7, pp , [20] C. P. Kelley, J. Cildress, C. Boake, and E. A. Noser, Overground and robotic-assisted locomotor training in adults wit cronic stroke: a blinded randomized clinical trial, Disability and Reabilitation: Assistive Tecnology, vol. 8, no. 2, pp , [21] R.S.Calabrò,S.Reitano,A.Leo,R.DeLuca,C.Melegari,and P. Bramanti, Can robot-assisted movement training (Lokomat) improve functional recovery and psycological well-being in cronic stroke? Promising findings from a case study, Functional Neurology, vol. 29, no. 2, pp , [22] J.J.Deeks,J.P.T.Higgins,andD.G.Altman, Analysingdata and undertaking meta-analyses, in Cocrane Handbook for Systematic Reviews of Interventions, Wiley, Hoboken, NJ, USA, [23] Official Bulletin of Lazio Region, n 56, Subject: Approval of te regional tariff for te compensation of ospital care services D. M [24] Italian Ministerial Decree of te 31st of December 1988 and modified wit te Italian Ministerial Decree of te 28t of Marc 1996, establised by te Italian Ministry of Finance. [25] M. Cenciarini and A. M. Dollar, Biomecanical considerations in te design of lower limb exoskeletons, in Proceedings of te IEEE International Conference on Reabilitation Robotics ICORR, pp , Zuric, Switzerland, July [26] World Healt Organization, Needs assessment for medical devices, in WHO medical device tecnical series, WHO, Geneva, Switzerland, 2011.

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