Robot-Assisted Stroke Rehabilitation

Transcription

1 American Heart Association International Stroke Conference, 2012, New Orleans Robot-Assisted Stroke Rehabilitation Albert Lo, M.D., PhD Departments of Neurology and Epidemiology Associate Director, Center for Restorative & Regenerative Medicine Brown University, Providence RI Providence VAMC

2 Outline Overview of robot rehabilitation trials Clinical trial design drives interpretation and relevance for clinical application VA ROBOTICS Lessons learned on dosing, control groups, durability, generalizability, feasibility and effectiveness 3

3 Robot Stroke Rehabilitation Studies To Date Why have there been so few big studies? Has clinical trial design been a limitation? What are the practical clinical implications of current data? 4

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5 Training Protocol Dose Intensity, frequency, total number of sessions Where does the training take place Inpatient, outpatient, home Inpatient duration may be limited Outpatient frequency may be limited Robot used independently or in combination Initial attempt to maximize dose and tolerability VA ROBOTICS - 36 sessions, 36,000 movements 6

6 Treatment Effects The means by which we decide if something works Outcome Selection - Impairment/Capacity - Performance in real life situations/ QoL Absolute Change from baseline while controlling for placebo-effect and testing-effect Relative - Compared to what? - Value-added from robot. Need an active control Where and when are the effects evident? Lab and life, durability--incorporation into daily life 7

7 Robot-Rehabilitation Studies What clinical trial factors affect interpretation for robot clinical use Challenges for robot trials linked with clinical trials for rehabilitation Overview of trials to date- key issues study design Cumberland Workshop Consensus (2009) 8 Lo (2012) Arch Phys Med Rehab In Pres

8 Robot rehabilitation Articles Search Method MEDLINE (up to- May 2011) Earliest January articles total Excluded device development and review papers 67 articles 24 devices 9

9 Sample Size 67 Robot Studies By Sample Size Studies 10

10 Cumberland Conceptual Framework for Evaluating Rehabilitaion Studies A retrospective investigation into why rehabilitation studies have not progressed to larger clinical trials Pilot consideration-of-concept - Represented by small case series Testing clinical feasibility and Potential benefit for a new device Development-of-concept - Includes a standardized description of the intervention, Control group, randomization, Blinded outcome assessments Demonstration-of-concept/ Proof of Concept MRCT - FDA phase II/III, Active control group, establishing best dose Determining effect size, Power calculation, clinically meaningful outcome Efficacy trial 11 Dobkin (2009) NNR 23:197 11

11 Pilot Robot Studies (35) Stroke MS CP SCI PD 12

12 Development of concept studies 24 studies 22 studies were on stroke All single site 12 robot types Primary considerations: Control group (active preferred), randomization, masked evaluators Only 5 of 24 had all 3 elements Only 6 studies enrolled 15 or more subjects

13 24 Development of Concept (24) Parallel Control Active Control Randomization Blinded Outcome 14

14 Demonstration of Concept/Proof MRCT Study N Clinical context Outcome Safety Blinded Intention to Treat Gait Trainer (Pohl, 2007) 155 In FAC Barthel Not specified Yes F, B Not F-U Yes ROBOTICS (Lo, 2010) 127 Out Fugl- Meyer AE; pain, spasticiy Yes Yes Lokomat (Schwartz, 2009) 67 In FAC Not specified Lokomat (Hidler, 2009) 63 Out Speed, 6 MW Yes, Nontreating Yes, but 2 excluded Con Not specified No No 15

15 Summary of Pilot Studies Effects Many with sample size around 20 Study Training sessions/format Most with an uncontrolled pre- post design Gait Virtually all show a positive effect Trainer Expected for an original report considering publication (Pohl) bias ROBOTICS Outpatient 3 Virtually none report on safety (Lo) Purpose is to launch the best devices, studied in the most Lokomat informative manner to larger more controlled (Schwartz) History tells us that even the most promising preliminary Lokomat data can not work once subjected to a RCT Outpatient, 3 (Hidler) Training Dose & Treatment i.e. Hormone replacement therapy Treatment frequency and context 20 combined Inpatient 7 days/week 36 independent days/week 30 combined Inpatient 5 days/week 24 independent days/week

16 Training Protocol Summary Common themes All training conducted in a clinic setting (not home) All used robots in a structured format 100% robot-assist, progressive (In-motion manus, Lokomat) Time-fixed robot (20min) and time-fixed conventional (gait trainer or Lokomat) All studies generally maximized dose (20-36 sessions) VA ROBOTICS and Hidler Lokomat include midpoint (dosing) Outpatient frequency 3 times/week (7-12 weeks) Inpatient frequency 5-7 times a week (3-6 weeks) Geographical feasibility (USA) No individual session longer 17 than 60 min

17 Treatment Effects Outcomes primarily, clinical assessments of impairment/capacity or skills or functional (Functional Ambulation Category) Very few reported safety outcomes (4/67), (1/4 for larger) All studies found absolute change from baseline Virtually all the pilot studies will show positive results 4 large studies with active controls 2 showed robot group better than conventional (categorical change on FAC, but not on gait parameters) 1 showed no difference (p= 0.08) 1 showed robot worse than conventional (p=0.002, p=0.03) 18 3 of 4 had post-training durability follow-up

18 Gait training studies stroke and gait characteristics Days Poststroke Baseline m/s End Experimenta l m/s End Active Control m/s Hidler Lokomat (Loko) 0.60 (PT) LEAPs Duncan DEGAS Pohl Scwartz Lokomat (LT) 0.64 (HE) FAC=0 19

19 Trying to draw conclusions across studies For severe gait impairment (0.13 m/s) or unable to walk without 2 person support (FAC=0) (Robot + Gait Training) better than (Gait training alone without BWSTT) For categorical change to independent ambulation. FAC 3 Gait impairment (approx m/s) (Gait training with BWSTT) better than (Lokomat) But maybe not better than non-intensity matched Home exercise Lokomat vs. Home Exercise not done. Suggests supported training (Robot- BWS-TT) for more severe individuals, transitioning to less need for support at higher function levels 20

20 Upper-extremity Training VA ROBOTICS No combination training. No clinic vs home training Severity of ROBOTICS cohort was worse than EXCITE. Difficult for direct comparison Planned for maximal dose. Planned Dose effect analysis Active control group (ICT) was different than others. Intensity Carry-over of goal-oriented movement Unintended consequence of efficient design- control groups We attempted to match robot intensity--feasibility Economic analysis Lo et al. (2010) NEJM 362:1772 provide context for value-added 21 from Rehabilitation

21 Fugl-Meyer Change Over 36 weeks Overall Mean Difference Robot(25) vs. UC(27) = 2.88, p=.016 Overall Mean Difference Robot(47) vs. ICT(46) = -0.58, p=.63

22 Perspective on VA ROBOTICS results We expected the robots training to yield greater gains Treatment effects for second phase, were closer to preliminary results data Sample size small in the world of Clinical trials Ultimate and dose treatment response was heterogeneous Aggregated results are an average Scatter plot data for individual results show Large, moderate, small positive gains No gains Negative Intensive Conventional is not regular OT

23 VA ROBOTICS Enrollment Timeline Years UC RT n = 27 n = 25 n = 47 n = 46 ICT Lo et al., (2010) NEJM 362:1772

24 Fugl-Meyer Change at 12 weeks Mean Difference = 2.17 p = Robot UC Robot ICT Mean Difference = p = 0.92

25 Robot therapy: smaller change in the first phase and larger in the RT n = 25 second n = 47 First phase n=25, 1 point Total average change for n= 47, (25+X) is 4 point Calculating for second phase only X = 7.4 points Don t have a control group for X X [25 (1) + 22(X)]/ 47= 4 points Solving for X = 7.4 points

26 Potential cost savings with more rehabilitation Average cost of additional therapy Usual Care $ 0 ICT $7,582 Robot $5,152 (p < 0.001) Average total healthcare cost after 36 weeks (therapy + all other healthcare utilization) Usual Care $19,098 ICT $12,364 Robot $12,679 (NS) Wagner et al. (2011) Stroke

27 Current Interpretation of Robot Rehabilitation Studies 1. Most Robot studies have been small 2. Device and engineering driven 3. Larger RCT studies will active control will be much more informative Recalibrate elevated pilot expectations --Realistic expectations for problems, real-world effectiveness and value added from robots or technology 4. First generation studies have been simple and have not taken advantage of additional features Primarily used to deliver high intensity of within session Necessary to reduce varibles 5. Many issues related to the evolution of 30 Rehabilitation Clinical Trials. Dual challenge of

28 Future speculation for Robots? 1. Best use for robots may mean integrating with conventional approaches and with our best understanding or recovery and rehabilitation 2. Future studies might incorporate robots to take advantage of repetition to support transitions to address specific objectives Heavy tedious early work in the clinic Practice and use at home with feedback and monitoring 3. Emphasis on treatment efficiency and effectivenss 4. Cost savings. Increased cost for labor 5. May need a new rehabilitation 31 paradigm shift

29 Future speculation for Robots? Lack of superiority of robots As a final statement is greatly exaggerated Steve Jobs: Newton to ipad Newton , $700-$1,200, 2MB -Tablet Technology evolved -Environment for tablet use changed as well -Wifi, 4G 32