Medical and Rehabilitation Innovations Exoskeletons in Spinal Cord Injury

BACKGROUND Restoration of ambulation ability has always been the Holy Grail in spinal cord injury (SCI) rehabilitation. Despite significant gains in life expectancy and health measures and some gains in durable medical equipment over the past 40 years, improvements in neurological recovery and gait restoration have been minor. Surveys continually reveal a strong desire by those with SCI to walk again, no matter how much time has passed since injury. Rehabilitation providers share the same goal of restoring ambulation. Recently implemented acute rehabilitation measures include body weight supported ambulation soon after injury even for those patients predicted to have zero to minimal neuro recovery (e.g. ASIA A SCI). This zeal to restore ambulation, while laudable, can blur the lines between good science and unattainable hope, diminishing the validity of the very outcomes some hope to promote. With the recent advent of robotic technology, there are a number of robotic ambulation devices being promoted as potential exoskeleton gait devices. The first to obtain Food and Drug Administration (FDA) approval was the ReWalk, and a number of others are pursuing similar clearance. Our review of the current state of exoskeleton technology revealed some exciting opportunities and some concerning gaps between clinical claims being made and science. It is vital to consider what one author surmised: “While there is much excitement around these new robotic exoskeletons, there are issues that may limit their utility both as a therapeutic device and as a mobility device. Some significant limiting factors include difficulty donning and doffing, problems transferring, slow and often rough movement, lack of dependability, and concerns surrounding pressure distribution and skin integrity. Researchers have identified four key topics for future development of exoskeletons: robust control, safety and dependability, ease of wearability or portability, and usability/acceptance. For example, if a person cannot easily use a device, or has problems with accepting a novel technology, it will likely be abandoned or not used to its full potential. For this reason, the wider acceptance of exoskeletons for both rehabilitation and function is dependent on the end user being central to design and development of the technology.”1 Device Overview Mobility devices for SCI are a varied category of durable medical equipment. Wheelchairs are presently the mainstay of mobility device for those who are unable to ambulate. They are quite efficient from an exercise physiology standpoint. For the group of patients being considered for exoskeleton devices (T7-L5), manual wheelchairs have been the standard device due to typical upper body strength. The advent of lightweight and sports wheelchairs has led to mobility capacity often much faster than normal ambulation (which averages 3 miles per hour). Gait devices, the utility of which depend on the neurological status and motivation of the patient, have been available for decades. Initial enthusiasm for these gait devices has often

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been tempered by key limitations in user acceptance and lack of broad usefulness of the particular device.2 Ankle-foot orthoses (AFO) and knee-ankle-foot orthoses (KAFO) are braces that passively fix or control the position of a joint. These allow a person with spinal cord injury to bear weight on or clear an otherwise paralyzed portion of the leg. The key word is “passive,” in that they assist stability or position of the limb without user control to allow weight bearing and swing. The mobility part of gait is accomplished by active use of non-paralyzed leg muscles to advance the leg in the case of lower paraplegia (L2-S1), or, in the case of higher level paraplegics with no intact leg muscles (T12 and above), by virtue of swinging the legs through using body momentum and crutches. The use of crutches limits what they can do or carry with upper extremities during gait. The individual adoption of the use of AFOs and KAFOs varies. Usage is often limited by the fact that wheelchair use is often more efficient and convenient compared to the use of braces, particularly for KAFOs. Hence, the early enthusiasm and desire for such gait-facilitating devices often dissipates with time. It is important to learn from this past history when considering new technologies. Newer electrical stimulation and robotic devices must overcome the demonstrated efficacy and convenience challenges of wheelchair options to prove effective in the long-term. Of late, there is great interest in gait devices that incorporate electrical stimulation to stimulate the paralyzed muscles to contract to assist gait and in externally powered braces to passively move the limbs to assist gait. These are not new concepts, but current and future computer technology and lightweight materials may make these technologies more practical. Electrical stimulation ambulation was tried in the 1990s by Jerrold Petrofsky, PhD, but this attempt did not result in large scale success. Since then functional electrical stimulation (FES) technology has taken a step forward, but current broad use of FES in ambulation devices is still limited by technical and clinical challenges such as muscle fatigue. Robotic ambulation is not dependent on active muscle contraction, but rather a battery powered brace. This is the subject of this paper. Currently, there are a number of exoskeleton devices in the market including Ekso, ReWalk, Indego, Rex, Berkley Bionics and Cyberdyne. The ReWalk exoskeleton device was the first to be approved by FDA.

LITERATURE SUMMARY The following summarizes FDA approval and medical literature available to date. The major questions to consider are: What are the factors supporting current exoskeleton devices as functional gait devices? What are the functional benefits and advantages of exoskeletons over existing wheelchairs and gait devices? What evidence-based data supports the lay press hype?

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FDA Approval: What It Means (and What It Does Not Mean) The FDA approved ReWalk through the de novo classification process—a regulatory pathway for novel, first-of-its-kind medical devices that are generally low-to moderate-risk.3,4 The FDA required Argo Medical Technologies, Inc., the manufacturer of ReWalk, to complete a postmarket clinical study, including a registry to collect data on adverse events related to the use of the ReWalk device, as well as prospectively and systematically assessing the adequacy of its training program. The study ReWalk submitted for FDA review was based on clinical data from 30 study participants where risks associated with ReWalk included “pressure sores, bruising or abrasions, falls and associated injuries, and diastolic hypertension during use.”4 FDA approval of the ReWalk Exoskeleton specified that “ReWalk is for people with paraplegia due to spinal cord injuries at levels T7 (seventh thoracic vertebra) to L5 (fifth lumbar vertebra) when accompanied by a specially trained caregiver. It is also for people with spinal cord injuries at levels T4 (fourth thoracic vertebra) to T6 (sixth thoracic vertebra) where the device is limited to use in rehabilitation institutions. The device is not intended for sports or climbing stairs.”4 One of the challenges of evaluating new technologies is to understand the meaning of FDA approval and whether such approval indicates broad or comparative effectiveness, a regulatory stamp of safety, or some combination of both. Some healthcare marketing uses FDA-approval to insinuate that the particular device or medication has crossed some high evidence-based medicine hurdle. The reality is that FDA approval is a requirement to marketing a medical product, whether it is a medication or a medical device. The FDA has been criticized by some drug and device companies on the one side as requiring too much red tape and research before allowing new products entering the market, while others allege a heightened bias towards the business interests of the pharmaceutical and device companies. The important distinction here is that FDA approval does not automatically suggest that a full, evidence-based review has been accomplished. Nor does it signify any comparative superiority to currently available alternatives. In fact, the FDA tiers safety risks wherein certain class categories may not require vigorous research or testing to achieve FDA approval. Furthermore, safety is not guaranteed by FDA approval, since applicants for approval need to submit only a limited number of studies showing product effectiveness, and they are not required to make available any existing studies that show their ineffectiveness. Thus, compared to the rigors of a systematic, scientific review that is the standard in evidence-based medicine, FDA approval does not require the same scientific rigor. Professionals should be aware of the limited significance of FDA approval. It does not subsequently require insurance companies to certify payment for a particular product. Nor does the FDA approval process require any comparative product studies to delineate which treatments are as effective and/or superior to each other. It is also important to understand

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that FDA approval of a product for a certain use does not certify that each and every claim made by the manufacturer is verified or confirmed. FDA approval is really about permission to bring a product to market and it is not a reimbursement approval. The existence of different exoskeleton devices with varying use of FES, brain machine interface, and light weight designs reveal that this technology is still very much investigational. Hype Versus Reality We see coverage on news shows, the internet and at medical conferences about paraplegics walking again thanks to new technology. These are powerful stories that tug at even the most hardened heartstrings. Independent gait and better health outcomes are touted. But gait independence can be exaggerated by the lay press and vendors. A closer look at the available scientific research indicates these health outcomes are still theoretical rather than proven. The FDA announcement speaks of assisted gait. The scientific data reveal slow gait speeds and functional limitations not clearly represented in the promotional materials. This kind of selective messaging may contribute to the future failure of adoption of this technology. There are several examples of these failures. The reciprocating gait orthosis (RGO), a hip-knee-anklefoot orthosis, and advanced reciprocating gait orthosis (ARGO) experience of the 1990s is a good example. Touted as a strong advancement in paraplegic gait devices, it ultimately did not live up to the hype generated by marketing efforts. A subsequent technology resulted in the IBot wheelchair that enabled SCI patients to stand and climb steps. It hit the market scene with widespread medical and functional claims, but with a $25,000 price tag it was not well received. The Segway was a motorized vehicle that sought acceptance within the healthcare community as an upright mobility device. It too suffered some from the overzealous, premature medical marketing and safety claims. There are various electroprosthesis or orthotics on the market for gait such as the Walk-Aide and the Bioness, particularly for foot drop and other central nervous system-localized paralysis. Despite initial excitement about these devices, adoption has been slow partly because they were more limited in usefulness and tolerance than marketed and partly due to their higher cost compared with existing devices. Current Claims and Evidence for Exoskeleton Gait Devices Claim Restores Walking

Findings Gait speeds documented at 1 mile per hour in controlled environments with assistance

Comment Normal walking speed is 3 miles per hour

Claims ability to ambulate in places not accessible to a wheelchair

Accessibility on different terrain likely limits this to level ground and shallow inclines

ReWalk study clinical data based

Study populations are small and not

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Restores Independence

Claims of Potential Use in the Community

Promotes Neurological Recovery

on 30 study participants4

randomized

ReWalk references some studies including a study with a “convenience sample” of 7 participants with T1-T12 paraplegia who had good results5 FDA approval specifies the need for “training and assistance from a caregiver”4

Studies would need to be compared against currently available forms of mobility including wheelchair mobility

Claims made about the social value of being able to stand eye to eye with others No research validation of safe use independently in the community over the long-term or independently

Gait requires a handheld assistive device which would limited functional activities Potential limits and dangers for use in the community include short battery life (6 hours), risk of mechanical failure, risk of software glitches or failures.

Most qualifying paraplegics do not need functional assistance; this device requires additional assistance

Studies would need to be compared against currently available forms of mobility If this were true, one might expect a significant decrease in rehabilitation length of stay.

No data to support this

Claim requires scientific randomized controlled studies. Similar claims about other recent technology were not verified, for example: • There are no controlled studies supporting that robotic devices facilitate speedier or more significant recovery than standard measures or less intense measures. In fact, though often touted to do so, even body weight supported gait training alone has not shown any superiority to more standard measures

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•

Safety

Not enough data. No major injuries widely reported. Research studies underway in highly controlled environments such as rehabilitation hospitals.

“Conclusion: subjects with subacute motor incomplete spinal cord injury reached a higher level of independent walking after over-ground training, compared with body weight supported treadmill training. More randomized controlled trials are needed to clarify the effectiveness of body weight supported gait training on walking, activities of daily living, and quality of life for subgroups of persons with an incomplete SCI”6

Risk of falls Risk of being stranded Risk of fractures or upper extremity injuries

As part of the ReWalk approval the FDA requires a post-market clinical study including a registry to collect data on adverse events related to the use of the ReWalk device and a prospective, systematic assessment of the adequacy of its training program

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Health Benefits: • Decrease in acute post SCI medical morbidity: skin breakdown, urological, GI, respirator, cardiovascular health • Decrease in chronic post SCI medical morbidity: skin breakdown, urological, GI, respirator, cardiovascular health, osteoporosis

Exercise Benefits

No documented, controlled comparative validation studies. Vendors tout potential health benefits such as preventing skin breakdown and fractures, but there are no studies validating this. A typical set of medical claims may be found online (e.g. http://www.businessinsider.com/ rewalk-ekso-bionic-suits-2014-7) where the speaker claims that the cost of the device is offset by saving from decreased skin breakdown and fractures.

The medical and physiological sequelae of SCI is well known and the need for and theoretical benefits of exercise is well established. There are existing means and challenges of exercise.7 Current claims made appear exacerbated and not compared to currently available technologies. Even the benefits of FES have proven modest.7 If proven true, one would expect a significant decrease in rehabilitation hospital average length of stay. For most of these measures, one could theorize potential equal and opposite unintended medical consequences, such as increase in urinary incontinence, orthotic related skin breakdown, symptomatic postural hypotension, soft tissue injuries, and upper extremity strain. It is for this reason that controlled research is necessary to validate any short and long-term health claims.

Studies currently underway

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Studies will need to compare exoskeleton use against currently available forms of medical care including compliance with skin precautions, cushions, standing frames, medications, nutrition. For example, therapeutic standing has been theorized to be beneficial for bone density, circulation, spasticity management. This is the reason that standing frames have been widely recommended. Studies would need to be compared against currently available forms of exercise such as standing with KAFO,

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wheelchair mobility FES bicycle, upper extremity ergometry. There are less intensive and costly options for exercise.7

PARADIGM OUTCOMES’ POSITION Gait is almost always rated as the most important goal in people with SCI, acute or chronic. Many gait technologies have been pursued over the decades, but have ultimately not been successful due to lack of adequate functional restoration of gait, excess energy expenditure, or inconvenience. The advent of exoskeleton gait devices is the latest technology that promises to “make paralyzed people walk again.” Whether exoskeletons meet that promise will depend on their success at overcoming the same basic obstacles as the technology that came before. That is, delivering adequately safe functional gait at a reasonable energy cost, causing minimal inconvenience of use, all at a realistic healthcare dollar cost. Many, but not all, of the currently available devices offer passive mobility in an upright position, but not technically active walking in the sense of propulsion by one’s own muscle contraction. Those that incorporate FES and provide muscle contraction have not overcome the problem of muscle fatigue. At the current time, gait speed is sub-functional, the ability to move about in all directions is sub-functional, and the provision of independence is not realized due to the need for personal assistance to use the device. Many claims about potential health benefits are not verified by controlled randomized studies, whether short-term or long-term, and no studies have shown these devices to be superior to currently existing forms of exercise (e.g. wheelchair mobility, standing frame, FES, standing frames, aquatics). Current device reliability, safety, and durability are unproven, and the equipment is cost-prohibitive. It is important to not rely on hopeful excitement at the possibility of upright mobility at the expense of proof in clinical effectiveness. While this is an exciting technology, valid research still needs to be done before promoting these devices for widespread use. Current health benefit claims appear premature. A stakeholder study found that “481 survey responses were analyzed, 354 from wheelchair users and 127 from healthcare professionals. The most highly rated reason for potential use or recommendation of an exoskeleton was health benefits.”1 For this reason, it is even more vital that the proposed health benefits be scientifically validated. From a clinical and managed care perspective, this research includes proof of effectiveness and healthcare value in the areas of gait function, safety, functional improvement, physiological exercise outcomes, and health benefits that are superior to already available resources and options.

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Financial Impact The following table displays the known cost ranges of exoskeleton devices. Retail Exoskeleton Cost Company

Low

High

Indego (Parker Hannifin) Rex (Rex Bionics) ReWalk (Argo Medical Technologies)

TBA TBA $65,000

TBA TBA $150,000

Ekso (EksoBionics)

$50,000

$130,000

The current exoskeleton device makers are cognizant that their products need to be competitively priced before full adoption will take place. It is anticipated that the price for these devices will continue to come down and most likely stabilize between $50,000 and $100,000. Some centers of excellence may use these devices as therapeutic modality while in treatment; however, it is currently being trialed as an investigational therapy modality. Please note that modalities used in therapy should not be associated with additional costs. That said, one cannot rule out the possibility that this would be prescribed and purchased for an injured worker and should be considered a modest claim cost risk. Other potential costs could include personal attendant care costs for training and assistance. Summary There currently is insufficient evidence-based medical data to explicitly support the use of robotic exoskeleton devices for paraplegics as home/community mobility devices. Most certainly, additional clinical studies validating the improved efficacy and comparative advantage in gait function, safety, functional independence and associated secondary health benefit outcomes are needed. The true safety profile, both medically and technologically, is not yet known, and the psychological benefit alone is not enough to justify the enormous cost of the device, training and personnel support needed to use it simply as a mobility device. Help: There is a personal, subjective psychological benefit stated by some persons using these devices stated as the ability to stand eye to eye, the ability to have upright mobility and the hope of better ambulation in the future. Hope: There is hope and excitement that the current technology can lead to more costeffective facilitation of active gait, independent gait, community mobility, and improvement of overall functional independence in the future. The companies which are developing these technologies speak of potential secondary health benefits with improvements in cardiovascular health, reduction in fat tissue, building of lean muscle mass, and improved bowel function. We

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hope the future clinical studies will help determine whether these devices will prove to show better outcomes with the aforementioned health benefits when compared to the currently available technologies and devices. Hype: Claims about improved neurological recovery and paraplegics walking again are inflated. Research studies do not yet demonstrate medical outcomes with improved urinary function, skin integrity, overall fitness and cardiovascular health, nor resultant reductions in prescription medication use or hospitalization, although some clinical trials are under way.

ENDNOTES References 1. A survey of stakeholder perspectives on exoskeleton technology; Journal of NeuroEngineering and Rehabilitation. 2014, 11:169, Jamie Wolff, et al. 2. Ambulation and Spinal Cord Injury; Physical Medicine and Rehabilitation Clinics of North America. 24 (2013) 355-370; Elizabeth C Harden PhD, et al. 3. De Novo Classification Process (Evaluation of Automatic Class III Designation), Draft Guidance for Industry and Food and Drug Administration Staff; Documentation issued on: August 14, 2014; U.S. Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health, Office of Device Evaluation 4. Press Announcements: FDA allows marketing of first wearable, motorized device that helps people with certain spinal cord injuries to walk http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm402970.htm 5. Exoskeletal-Assisted Walking for Persons with Motor-Complete Paraplegia; VA Rehabilitation Research and Development National Center of Excellence for the Medical Consequences of Spinal Cord Injury; Ann M. Spungen, et al. 6. Body Weight-Supported Gait Training for Restoration of Walking in People with an Incomplete Spinal Cord Injury: A Systematic Review. Review Article; Journal of Rehabilitation Medicine. 2010; 42: 513-519, Monique Wessels, MSc1, et al. 7. Activity and Fitness in Spinal Cord Injury: Review and Update; Current Physical Medicine and Rehabilitation Reports. (2014) 2:147-157, Spinal Cord Injury Rehabilitation, Sue Ann Sisto & Nick Evans

Acknowledgements Special thanks to the Paradigm Medical Directors who contributed to this paper, including David Apple, MD, Pamela Ballard, MD, and Kenneth Parsons, MD, as well as the facilitators Laurie Anderson, Chris Anderson, Michael Choo, MD, and Steven Moskowitz, MD. © 2014. Paradigm Management Services, LLC (“Paradigm”). No part of this publication may be reproduced, transmitted, transcribed, shared, disseminated, summarized, stored in a retrieval system, adapted, or translated into any language in any form by any means without the written permission of Paradigm. Trademarks, service marks, products names, company names or logos of Paradigm are protected by trademark and other laws of the United States, as well as international conventions and the laws of other countries.

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