Artificial Lumbar Disc Replacement
Transcription
Artificial Lumbar Disc Replacement
Horizon Scanning Report Artificial Lumbar Disc Replacement (update) January 2006 <TITLE OF REPORT> - <MONTH YEAR> © Commonwealth of Australia [2006] This work is copyright. You may download, display, print and reproduce this material in unaltered form only (retaining this notice) for your personal, non-commercial use or use within your organisation. Apart from any use as permitted under the Copyright Act 1968, all other rights are reserved. Requests and inquiries concerning reproduction and rights should be addressed to Commonwealth Copyright Administration, Attorney General’s Department, Robert Garran Offices, National Circuit, Canberra ACT 2600 or posted at http://www.ag.gov.au/cca Electronic copies can be obtained from http://www.horizonscanning.gov.au Enquiries about the content of the report should be directed to: HealthPACT Secretariat Department of Health and Ageing MDP 106 GPO Box 9848 Canberra ACT 2606 AUSTRALIA DISCLAIMER: This report is based on information available at the time of research and cannot be expected to cover any developments arising from subsequent improvements to health technologies. This report is based on a limited literature search and is not a definitive statement on the safety, effectiveness or costeffectiveness of the health technology covered. The Commonwealth does not guarantee the accuracy, currency or completeness of the information in this report. This report is not intended to be used as medical advice and it is not intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute for a health professional's advice. The Commonwealth does not accept any liability for any injury, loss or damage incurred by use of or reliance on the information. The production of this Horizon scanning report was overseen by the Health Policy Advisory Committee on Technology (HealthPACT), a sub-committee of the Medical Services Advisory Committee (MSAC). HealthPACT comprises representatives from health departments in all states and territories, the Australia and New Zealand governments; MSAC and ASERNIP-S. The Australian Health Ministers’ Advisory Council (AHMAC) supports HealthPACT through funding. This Horizon scanning report was prepared by staff from the Australian Safety and Efficacy Register of New Interventional Procedures – Surgical (ASERNIP-S). 2 Table of Contents Background ......................................................................................1 Background to the Condition ...................................................................... 1 Description of the Technology ................................................................... 1 Treatment Alternatives.....................................................................5 Existing Comparators ................................................................................... 5 Clinical Outcomes............................................................................6 Effectiveness .................................................................................................. 6 Safety.............................................................................................................. 12 Potential Cost Impact .................................................................... 18 Cost Analysis ................................................................................................ 18 Ethical Considerations ................................................................... 18 Informed Consent ....................................................................................... 18 Access Issues ................................................................................................ 18 Training and Accreditation ............................................................ 18 Training ......................................................................................................... 18 Clinical Guidelines....................................................................................... 19 Limitations of the Assessment ....................................................... 19 Search Strategy Used for Report ............................................................... 19 Availability and Level of Evidence ........................................................... 20 Sources of Further Information...................................................... 21 Impact Summary............................................................................22 Conclusions ....................................................................................22 References ......................................................................................24 Appendix A: Table of Key Efficacy and Safety Findings..............29 Artificial lumbar disc replacement Background Background to the Condition Lower back pain can result from many factors, including: structural disease, neoplasms, referred pain to the spine, infection, inflammatory disease, and metabolic disorders (Speed 2004). Most types of lower back pain are associated with degeneration of the intervertebral disc (Fairbank 2002). Numerous therapies are available to treat lower back pain, including analgesic and antiinflammatory medication, behavioural and exercise therapies, surgery and spinal cord stimulation (Boden et al. 2004; Bogduk 2004). Surgical management has been mostly reserved for patients in whom other treatment options have failed. The main surgical treatment is fusion of the affected vertebral disc space, which was also used in other joints (eg. knee, hip) until reliable arthroplasty techniques were developed (Szpalski et al. 2002). Lumbar arthroplasty, or replacement of the disc with an artificial intervertebral disc, has potential advantages. These include maintenance of a more physiological range of movement and load distribution in the lumbar spine (Boden et al. 2004). The number of patients receiving artificial lumbar disc replacements has dramatically increased in recent years, with an ASERNIP-S report and a systematic review of the literature published in 2003 (de Kleuver et al. 2003). However, a number of studies have been published in the intervening period and this report is an update including more recently published results. Description of the Technology The intervertebral disc is not a simple joint, but a mixed structure consisting of a peripheral collagenous band (annulus fibrosus), uniting the adjacent vertebral endplates, and a central core (nucleus pulposus). (Szpalski et al. 2002) The artificial disc needs to: restore disc height and decompress neural structures; realign vertebral bodies; and by precise positioning of the device, restore the relationship between sagittal balance, movement and the guiding function of the facet joints. In addition, artificial discs need to have a long lifespan as a patient may live for many years after implantation of the disc. While experimental techniques for disc replacement have been used since the 1950s (Blumenthal et al. 2002), major development of artificial lumbar discs only began in the 1980s (Boden et al. 2004). 1 Artificial lumbar disc replacement This report is restricted to the artificial lumbar intervertebral discs which have been used clinically. These include: LINK SB Charité The artificial lumbar disc with the longest record of use and greatest number of cases worldwide is the Charité III prosthesis. In September 1984, the Charité I artificial disc was implanted for the first time in a patient at the Charité Hospital in Berlin (Link 2002). The Mark –I and –II implants were manufactured in the former German Democratic Republic only, had problems with migration and metal fatigue fractures, and were never commercially available. LINK (Waldemar Link GmbH and Co, Hamburg, Germany) started production of the LINK SB Charité III disc in 1987, with the company acquired by DePuySpine in June, 2003. The Charité III (DePuySpine, Inc. Raynham, Massachusetts, USA) artificial disc has been widely used in Europe and the United Kingdom. The US FDA accepted the premarket approval application for the Charité III artificial disc on June 3, 2004, with conditions including: following the patients enrolled in the investigational device exemption (IDE) study for at least two years; providing patients with documentation describing the implant; a post market in vitro study to assess wear debris; and a consideration of required surgeon training (FDA 2004). The Charité III disc consists of a biconvex ultra-high-molecular-weight polyethylene nucleus with a radio-opaque metallic ring. This interfaces with two endplates of cobaltchromium-molybdenum alloy, coated with titanium and hydroxyapatite and primarily fixed by ventral and dorsal teeth. The plates are currently available in five footprint configurations adaptable to the size of the vertebral endplates, each with four available angles (0,5, 7.5 and 10o), allowing for built-in lordosis with variations of 0o to 20o (Geisler et al. 2004). Charité III artificial disc (used with permission of DePuySpine Inc., USA) 2 Artificial lumbar disc replacement ProDisc II The ProDisc was developed by Dr Thierry Marnay, a French spine surgeon, in the late 1980s. It was developed by Spine Solutions Inc., later acquired by Synthes-Stratec in February, 2003. ProDisc II (Synthes-Stratec, Oberdorf, Switzerland) was launched in the European market in December 1999, and since that time more than 2000 ProDisc devices have been implanted in Europe (Boden et al. 2004). A multicentre FDA IDE study began in the US in October 2001. In February, 2003, the ProDisc® was being sold in 26 countries in Europe, Asia Pacific, Latin America and South Africa (Synthes-Stratec 2003). The ProDisc consists of two metal alloy endplates with midline keels. These are impacted into the surgically evacuated disc space, then an ultra-high molecular weight polyethylene domed component is snap-fitted into the inferior endplate. Assembly is performed inside the disc space with the space internally distracted (separated). There are two endplate sizes (medium and large), three heights of the polyethylene component (10, 12 and 14 mm) and two lordosis angles (6o and 11o). Minimal access approaches are possible and the ProDisc II is the only artificial disc being investigated for multiple level lumbar disc disease (spine-health.com 2004). Maverick The Maverick (Medtronic Sofamor Danek) artificial disc is a two piece metal-on-metal design, using a smaller and more posteriorly placed rotational centre. (Boden et al. 2004) Two large keels are used for rotational control, similar to the ProDisc II. The cobaltchromium-alloy components are coated with hydroxyapatite. A four-in-one guide instrument maintains intraoperative lordosis, measures depth and height distraction and guides chiselling during insertion. More than 120 Maverick discs have been implanted in Europe (Boden et al. 2004), where clinical series are now being studied. A nationwide US clinical trial was started in April 2003, to assess the safety and efficacy of the disc. FlexiCore The FlexiCore artificial disc was developed by SpineCore, which was acquired by Stryker in July 2004. The FlexiCore disc (Stryker Corp. Kalamazoo, MI, USA) is a metal-onmetal device which is inserted as a single unit. The superior and inferior parts are linked by a ball-and-socket joint, and can be implanted from a straight anterior or anterolateral direction. This offers the ability to manipulate the position of the implant within the intervertebral space. Domed baseplate surfaces are shaped to approximate the concavities of the vertebral body endplates, and coated with titanium plasma spray to assist bone ingrowth. A US FDA IDE study is currently underway for patients with single-level disc disease. 3 Artificial lumbar disc replacement Acromed Acroflex Clinical results using Acroflex Acromed (DePuy Acromed, Raynham MA, USA) artificial discs were published in 1993 (Enker et al. 1993). This publication states that the disc was being re-designed so that only a single piece of rubber was used as the inner core component. AcroFlex discs made from titanium/polyolefin have been implanted into patients in Adelaide, Australia (Freeman et al. 2001). However, clinical development of this disc has been terminated. Since there are patients in whom this disc has been implanted, the clinical studies are included in this report. The Procedure The precise method of implantation of the artificial lumbar disc can vary. Generally, an anterior retroperitoneal approach is used, via a small incision below the umbilicus. Once the disc is visualised, it is either partially or fully excised (depending on the prosthesis used). In most cases the vertebral endplates and surrounding spinal ligaments are preserved. Minimally invasive approaches for implantation of the Charité III and ProDisc II have also been used (Buttner-Janz 2002; Mayer et al. 2002). Intended Purpose The purpose of the artificial lumbar intervertebral disc is for replacement of the disc where surgically indicated, i.e. in patients with diseases involving the lumbar intervertebral disc. Clinical Need and Burden of Disease • • It has been recently estimated approximately 79% of Australian adults suffer from lower back pain at some time during their life (Walker et al. 2004). Patients who may benefit from artificial lumbar disc replacement are those with severe back pain, where other treatments have not been successful. These patients may not have any other treatment options. Stage of Development • • The FDA in the US have recently approved the use of the Charité III artificial disc, with a requirement for DePuy Spine to conduct a post-approval study to assess the product’s long-term safety and effectiveness, including its impact on other discs and on the bony structures on the back of the spine (FDA 2004). The FDA is expected to have approved the ProDisc II artificial disc by 2005, and several other companies are also developing artificial lumbar discs for clinical use. The Charité artificial lumbar disc has had TGA approval in Australia since 1995 (ARTG Number 96121; Product ID 115765). As of September 2004, over 600 4 Artificial lumbar disc replacement • • • Charité artificial lumbar discs have been implanted in Australia (personal communication). The ProDisc II artificial lumbar disc is being marketed in Australia by Taylor Bryant (Taylor Bryant 2004). As of March 2004, the Medicare Benefits Branch has agreed to fund disc replacement surgery as an interim measure until the FDA research findings are released, when ongoing funding will be reviewed. The MBS item numbers 48660 or 48669 in association with 48684 for spinal disc replacement have been recommended for use. The Medical Services Advisory Committee (MSAC) recently commenced an analysis of spinal disc replacement, with the findings expected to be released in 2005. Treatment Alternatives Existing Comparators There are many non-surgical alternatives for lumbar intervertebral disc disease (eg. physiotherapy, analgesia, anti-inflammatory medication), however, some patients remain in considerable pain with surgery the only remaining option. The main surgical treatment used has been spinal fusion, with proposed advantages of prosthetic disc replacement compared with spinal fusion being: • • • • • Maintenance of range of motion for the affected spinal unit. Proper kinematics and load sharing properties of the functional spinal unit could be maintained. Mobility of adjacent discs may be preserved, which could delay the onset of accelerated degenerative changes in adjacent levels, a common occurrence following spinal fusion. Sources of autoimmune and or inflammation-provoking substances emanating from the degenerated disc may be removed if the disc itself is excised and replaced. There is a lack of predictable pain relief following spinal fusion. Unsatisfactory results from spinal fusion, such as pseudoarthrosis and bone graft donor site complications, could be avoided (Boden et al. 2004). The other relatively new surgical option for patients with lumbar intervertebral disc disease is disc nucleus replacement, which may allow less invasive surgery to be performed versus replacement of the entire disc (Bertagnoli and Schonmayr, 2002). This procedure is beyond the scope of the present report. 5 Artificial lumbar disc replacement Clinical Outcomes There were 28 studies in total identified: one systematic review; 17 studies using the Charité III (two RCTs, one non-randomised comparative study and 14 case series); 7 studies using the ProDisc II (two single centre reports from the multicentre RCT and five case series); one case series using the Maverick disc; and two studies used two different Acroflex artificial discs. Effectiveness Clinical outcome The definition of clinical success varied between the studies; in some studies the criteria used to define success were not stated at all. Results are given according to the clinical success reported in each study, but it should be noted these numbers may not be directly comparable. Details of the individual study profiles are given in Appendix A. Charité III The RCT conducted by Blumenthal et al. (2005) comparing the Charité III artificial disc versus spinal fusion surgery with the BAK titanium cage (control) reported that patients of the Charité III group achieved a statistically greater improvement (p<0.05) in ODI and VAS scores compared to the control group at all time points except for the 24 month follow-up. Overall clinical success (defined by ≥25% improvement in ODI scores at 24 months compared to preoperative scores, no device failure, no major complications and no neurological deterioration compared to preoperative status) was achieved in 57.1% of patients in the Charité III group and 46.5% of the control group (p<0.0001). In the subset patients who completed the 24 months follow-up, overall clinical success was significantly greater in the Charité III group (63.6%) compared to the control group (56.8%) (p=0.0004). Neurological complications from this study was described previously by Geisler et al. (2004), where no significant differences in neurological status were reported between the groups (79% (141/179) of Charité III versus 82% (65/79) of BAK patients had no change in neurological status at 24 months) (Geisler et al. 2004). In a case series, Muschik & Meergans compared patients having Charité replacement discs because of degenerative disc disease (DDD) or postnucleotomy syndrome (PNS) (Muschik and Meergans 2003). There were 79% (23/29) of DDD patients with a complete or satisfying improvement versus 40% (4/10) in the PNS group. 6 Artificial lumbar disc replacement In 12 of the 17 case series with clinical outcome reported, Charité disc replacement resulted in 0% to 100% of patients achieving clinical success, with a median value of 75% (see Table 1). In four studies the clinical success was not stated. The lowest rate of success was in a study in which patients with complications were admitted to a specialist centre, therefore the group were a biased sample (van Ooij et al. 2003). Unsatisfactory results were found in 0% to 100% of patients, with a median value of 11%. Table 1: Clinical outcomes after Charité disc replacement in the included case series Study Caspi et al. 2003 David 2003 Kim et al. 2003 Muschik & Meergans 2003 Pimenta et al. 2003 Su et al. 2003 van Ooij et al. 2003 Buttner-Janz et al. 2002 Hopf et al. 2002 Scott-Young & Tan 2002 Sott et al. 2000 Zeegers et al. 1999 LeMaire 1997 Mean follow-up Patient no Clinical Success* 1-11 months 26 months 53 months n=20 n=21 n=5 DDD: n=29 PNS: n=10 n=55 n=31 n=26 6 months-13 years 14.7 months 20 months 48 months minimum 2 years 51 months n=20 n=35 n=86 n=14 n=46 n=105 68% 100% 100% DDD: 79% PNS: 40% not stated 94% 46% mean 53 months (range 1 month-10 yrs) 0% mean 91 months (range 15-157 months) 95% not stated 84% 71% 70% 79% 48 months 4 years >6 months 2 years Unsatisfactory outcome 20% 0% 0% DDD: 21% PNS: 40% not stated 0% 100% mean 91 months (range 15-157 months) 5% not stated 14% 30% 15% Ross et al. 1997 3 years not stated not stated Cinotti et al. 1996 3.2 years n=46 63% 7% Griffith et al. 1994 11.9 months n=93 not stated not stated David et al. 1993 minimum 1 year n=22 65% not stated *: clinical success as defined by the authors; DDD: degenerative disc disease: PNS: post-nucleotomy syndrome ProDisc II Two separate centres have published initial results from the FDA IDE multicentre RCT comparing ProDisc II implantation versus spinal fusion. In both studies the VAS and Oswestry scores significantly decreased in both groups, with a more rapid reduction in the ProDisc II patients. The ODI score was significantly reduced by 3 months in the ProDisc II versus 6 months in the fusion group, but at 24 months the ODI scores were 25.8 in the Charité group versus 30.1 in the BAK group (p=0.54) (Delamarter et al. 2003). There were five case series using the ProDisc II artificial disc. Clinical success ranged from 0% to 100%. The 0% success was in a report of only two patients, both having complications (Aunoble et al. 2004). Without this study, success rates were 83% to 100%. In one study the surgery was performed using a minimally invasive technique (Mayer et al. 2002). 7 Artificial lumbar disc replacement Table 2: ProDisc II Clinical Results Study Bertagnoli et al. 2005 Aunoble et al. 2004 Tropiano et al. 2003 Bertagnoli & Kumar 2002 Mayer et al. 2002 Mean follow-up 31 months (median) 4-20 months 1.4 years 3 months to 2 years 5.8 months Patient no 104 Clinical Success 96% Unsatisfactory outcome 4% 2 53 108 0% 100% 98% 100% 0% 0% 34 83% 17% Other implants In Enker et al. (1993) six patients received Acroflex Acromed discs (AcroMed Corporation, Cleveland, USA), with good to excellent results in three patients, fair results in one patient, and a poor result in two patients. Freeman et al. (2001) used an AcroFlex disc in eleven patients, with an average improvement of 39% in VAS and 12 points in ODI score at a minimum of 12 months follow-up. One paper in abstract form only was available describing clinical use of the Maverick disc prosthesis. Discs were implanted in 30 patients, with an 86% improvement in Oswestry score at one year, and a reduction in VAS (LeHuec et al. 2003). Hospital stay and operative times Charité III Hospital stay and operative times were reported in subgroups of the RCT comparing Charité III versus BAK surgery. In Blumenthal et al. (2003) the operative times in the first 57 Charité III patients were a mean of 95.2 minutes at L4-L5 (n=12) and a mean of 74.4 minutes at L5/S1 (n=45, p<0.05). In McAfee et al. (2003) times were only given for the combined groups and not for the separate procedures. Surgery length for the combined groups was a mean of 88.4 minutes (range 57-137 minutes) and hospital stay a mean of 3.03 days (range 2-6 days) (n=41 Charité III and n=19 BAK, total n=60) (McAfee et al. 2003a). In the 2005 update, Blumenthal et al. (2005) reported a mean operative time of 110.8 minutes for Charité III patients (n=205) with mean hospital stay of 3.7 days. Operating times were stated in two case series: a mean of 180 minutes (Kim et al. 2003) and 86 minutes (Hopf et al. 2002). Length of hospital stay was given in only one study, with a mean of 16.8 days (Hopf et al. 2002). 8 Artificial lumbar disc replacement ProDisc II In a subgroup of the RCT, hospital stay and operative times were reported to be shorter in the ProDisc II versus fusion patients (Zigler 2003). In the ProDisc II case series, mean operative times were 104 (Tropiano et al. 2003) to 131 minutes (Mayer et al. 2002); mean hospital stay was 9 days (Tropiano et al. 2003) to 12 days (Mayer et al. 2002). Acroflex In the study using the more recent Acroflex disc, mean operating time was 135 minutes and hospital stay 6.3 days (Freeman et al. 2001). Range of Motion Range of Motion measures the degree to which a patient can perform movement of flexion, extension, lateral bending, and spinal rotation. The range of motion was most commonly measured using flexion-extension radiographs. Charité III Patients with the Charité disc had greater flexion-extension range of motion at 24 months versus the BAK patients (mean 7.4o [5.28o] (n=179) versus 1.1o [0.87 o] (n=79) (assumption made that all patients at 24 months had flexion-extension measurements performed). (Geisler et al. 2004) Patients with the Charité disc had greater flexion-extension range of motion at 24 months versus the BAK patients (mean 7.4o [5.28o] (n=179) versus 1.1o [0.87 o] (n=79) (assumption made that all patients at 24 months had flexion-extension measurements performed). McAfee et al. (2005), reported that Charité III patients attained a 113.6% improvement in range of motion at 24 months (measured by lateral flexion/extension films) compared to preoperative measurements (13.6% increase). Six case series reported vertebral mobility following Charité III implantation. Average mobility values of 9o or 12o (Cinotti et al. 1996; David 2003; Su et al. 2003) or a range of 3o to 9o (Caspi et al. 2003) were found. In Buttner-Janz et al. (2002) the mean value for unisegmental implantation was 6.8o and for bisegmental implantation 5.8o (Buttner-Janz et al. 2002). LeMaire (1997) reported the range of motion at L4/L5 was 12o and 9.5o at L5/S1. Mobility in patients following Charité III implantation for degenerative disc disease was 8o , and 6o for patients with postnucleotomy syndrome (Muschik and Meergans 2003). 9 Artificial lumbar disc replacement ProDisc II In the study reporting initial results from the RCT, at six to 15 months follow-up Delamarter et al. (2003) found greater motion at the L4/L5 segment in ProDisc II (n=35) versus fusion patients (n=18, p<0.05). A similar trend was seen at L5/S1, but this did not reach statistical significance. In another subgroup, Zigler et al. (2003) stated that at six months ProDisc II patients (n=28) had significant improvement in range of motion compared to preoperative values, and better motion than the fusion patients (n=11). Two case series reported range of motion after ProDisc II implantation. In Tropiano et al. (2003) values were 8o at L5/S1 (range 2-12o) and 10o at L4/L5 (range 8-18o) (n=53). The other study reported average range of motion at four levels: 12o (range 9-15o) at L2/L3; 10o (range 8-15o) at L3/L4; 10o (range 9-13o) at L4/L5; and 9o (range 2-13o) at L5/S1 (n=108) (Bertagnoli and Kumar 2002). 10 Artificial lumbar disc replacement Other implants Enker et al. (1993) stated patients with Acroflex Acromed implants had an average lateral flexion/extension of 8o (range 2-16o). No values were given by Freeman et al. (2001), although it was stated that ten of eleven patients had satisfactory movement of the vertebral motion segment, as shown by cinefluoroscopy (Freeman et al. 2001). In the one study using the Maverick implant, the range of motion was a mean of 6o [4o] (range 3-12o) (LeHuec et al. 2003). Secondary Surgery Charité III In a subgroup of the RCT, McAfee et al. (2003) reported no patients required additional spinal reconstructive surgery in either the Charité III (n=41) or BAK (n=19) groups at one to three years follow-up. Blumenthal et al. (2005) reported that device failures necessitating reoperation, revision or removal was detected in 11 Charité patients (5.4%). In addition to this, approach related complications were noted in 20 (9.8%) Charité patients. In the Charité III case series, secondary surgery was reported in nine studies (see Table 4). The incidence of secondary surgery was between 0% and 56%. Reasons for further surgery included disc migration (Caspi et al. 2003), endplate fracture (LeMaire et al. 1997) and insertion of a smaller prosthesis (Cinotti et al. 1996). In a group of referred patients with complications, 56% had secondary surgery, with four patients having removal of the prosthesis and secondary salvage procedures in another 11 patients (van Ooij et al. 2003). Table 4: Secondary surgery in case series following Charité III implantation Study Caspi et al. 2003 Re-operation 10% (2/20) Kim et al. 2003 Muschik & Meergans 2003 Van Ooij et al. 2003 0% (0/5) 5% (2/39) 56% (15/27) Zeegers et al. 1999 24% (12/50) LeMaire 1997 1% (1/105) Ross et al. 1997 Cinotti et al. 1996 Griffith et al. 1994 4.3% (2/46) 2% (1/46) 3% (3/93) Reason Disc migration related to incomplete severing of post-longitudinal ligament (n=1) and fracture of the lower endplate (n=1). Posterior subluxation of the implant (n=1) and fusion after 4 months (n=1). Removal of prosthesis (n=4) and second spinal reconstructive salvage procedure (n=11) At segment with prosthesis (n=6); at another level (n=1) or because of complications (n=3). Revised to fusion because of an endplate fracture. not stated Revised to a smaller prosthesis. Revised to percutaneous nucleotomy, foraminoplasty and A-P spinal fusion 11 Artificial lumbar disc replacement ProDisc II Delamarter et al. (2003) reported no patients required revision surgery after either ProDisc II or spinal fusion surgery. Two case series reported secondary surgery following ProDisc II implantation. In Aunoble et al. (2003) both patients had spinal fusion surgery because of dislocation of the polyethylene core of the artificial disc (Aunoble et al. 2004). Tropiano et al. (2003) found 6% (3/53) of patients required secondary surgery, one for a vertebral body fracture and two patients for malposition of the disc prosthesis (Tropiano et al. 2003). Other implants In Enker et al. (1993) there was one patient (1/6) requiring re-operation as a result of a fracture through the rubber core of the Acroflex Acromed artificial disc. Freeman et al. (2001) did not state whether or not secondary surgery was necessary in any patients. Le Huec et al. (2003) reported no patients required removal or revision of the Maverick artificial disc out of thirty patients followed up to one year postoperatively. Safety Many of the complications following artificial lumbar disc replacement are the same as after any form of lumbar surgery, for example damage to the blood vessels or nerves in the area of surgery. However, there were also device specific complications, such as disc migration or dislocation, and device failure. Charité III In the RCT, no difference was seen in neurological adverse events in patients having Charité III versus BAK surgery (16.6%, 34/205 of Charité III versus 17.2%, 17/99 of BAK patients) (Geisler et al. 2004). Of these, 1.5% (3/205) of events in the Charité III patients were related to the device, with one (a nerve root injury) classified as severe. A centre participating in this RCT also presented results from their cohort, reporting one death unrelated to the spinal procedure, and one patient with postoperative small bowel obstruction of uncertain origin (McAfee et al. 2003a). It was stated adhesions of the greater omentum were found at surgery, and that the use of the self-retaining Thompson retractor to retract the bowel is now ‘curtailed’. It was not stated which groups these patients were from. In the total cohort there was one case each of: retrograde ejaculation, depression, adynamic ileus requiring a nasogastric tube, adynamic ileus not requiring a nasogastric tube, urinary tract infection, epididymitis, lateral epicondylitis and degenerative changes at the vertebral level above (McAfee et al. 2003b). 12 Artificial lumbar disc replacement The 2005 update by Blumenthal et al. (2005) on this RCT reported no serious device failures that resulted in death or injury. However, device failures that resulted in reoperation, revision or removal occurred in 11 Charité III patients (5.4%). Collapse or subsidence of the Charité III disc into adjacent vertebrae occurred in 7 (3.4%) patients and there was one case (0.5%) of implant displacement (Blumenthal et al. 2005). 13 Artificial lumbar disc replacement Table 3: Charité III complications in case series Study Patient no 20 Total complications Device related complications 5 (25%) David 2003 Kim et al. 2003 Muschik & Meergans 2003 21 5 39 2 (10%) 0% 4 (10%) Pimenta et al. 2003 55 11 (20%) Su et al. 2003 31 not stated 27 (early) 26 (late) 9 (33%) early 26 (100%) late Buttner-Janz et al. 2002 Hopf et al. 2002 Scott-Young & Tan 2002 Sott et al. 2000 20 35 86 14 Zeegers et al. 1999 46 9 (45%) not stated not stated 1 (7%) minor complication 8 (15%) permanent LeMaire 1997 105 11 (10%) Cinotti et al. 1996 46 21 (46%) Griffith et al. 1994 93 53 (57%) total 30 (32%) not device related 16 (17%) equivocal 2 (10%) disc migrations (n=2) and device failure (n=1) not stated 0% 1 (3%) posterior subluxation of the implant (n=1) 2 (4%) implant subsidence (n=2) 1 (3%) displacement of core without clinical symptoms (n=1) 2 (7%) early 1 (3.5%) asymmetrical insertion 1 (3.5%) dislocation of disc 26 (100%) late 18 (67%) subsidence 2 (7%) disc migration 10 (38%) prosthesis too small 1 (3.5%) disc dislocation 2 (7%) device breakage 1 (3.5%) subluxation 3 (12%) overdistraction of segment not stated not stated not stated 1 (7%) implant migration 2 (4%) poor implantation 3 (3%) 46 (44%) varying disc migration (not clinically significant) 1 (2%) disc migration 4 (9%) undersized prosthesis 9 (20%) subsidence on radiograph 1 (1%) implant failure 5 (4%) implant migration 1 (1%) implant dislocation Caspi et al. 2003 van Ooij et al. 2003 Complications were reported in 13/15 of the other Charité III case series (see Table 3). Total complications rates ranged from 0% to 100%. The zero complication rate was from a study including only five patients, while van Ooij et al. (2003) reported a selected group of 26 patients, all presenting at a specialist clinic with complications. Disregarding these two studies, complication rates were between 10% (David 2003; LeMaire et al. 1997; Muschik and Meergans 2003) and 52% (Griffith et al. 1994) in the remaining studies. 14 Artificial lumbar disc replacement Device-related complications were between 0% (Kim et al. 2003) and 100% (van Ooij et al. 2003) in the Charité III case series. The most common complication in van Ooij et al. (2003) was subsidence of the disc, occurring in 67% of patients. Other complications included asymmetrical insertion, disc migration, the prosthesis being too small and device breakage. Without these two studies, device-related complications occurred in 3% (Su et al. 2003) to 10% (Caspi et al. 2003) of patients. Complications in these studies included: implant migration or dislocation, implant subsidence, poor implantation, and incorrect size of prosthesis used. Implant failures were reported in three studies (Caspi et al. 2003; Griffith et al. 1994; van Ooij et al. 2003). Caspi et al. (2003) stated migration of the disc was because of incomplete severing of the post-longitudinal ligament in one patient and following a small fracture of the lower endplate in another patient; in both cases a larger prosthesis was inserted. ProDisc II Two studies presented initial results from their centres, involved in the multicentre RCT comparing ProDisc II implantation versus spinal fusion. Neither study reported total complications rates in the patients. In Delamarter et al. (2003) there were no incidents of implant migration, breakage, or mechanical failure after disc replacement. Bertagnoli et al. (2005) reported no incidents of device related complications while the other four case series reported complications following ProDisc II implantation. Total complication rates were between 1% and 9%. (Bertagnoli and Kumar. 2002; Mayer et al. 2002; Tropiano et al. 2003). Device-related complications were between 0% (Bertagnoli and Kumar 2002) and 100% (Aunoble et al. 2004). In the latter study only two patients were included, both of whom had dislocation of the disc. Table 4: ProDisc II Complications Study Aunoble et al. 2004 Tropiano et al. 2003 Bertagnoli & Kumar 2002 Mayer et al. 2002 Patient no Total complications 2 100% 53 108 34 5 (9%) 1 (1%) 3 (9%) Device related complications 100% dislocation of disc 3 (6%) 0% 0% Other implants: In Enker et al. (1993) there was one patient (1/6) with an implant failure, a fracture through the rubber core of the Acroflex Acromed artificial disc. However, there were no cases of local or systemic complications. Freeman et al. (2001) stated there was an early partial displacement of the AcroFlex artificial disc in 1/11 patients, but no operative complications occurred. In thirty patients with a Maverick disc prosthesis, there was one complication (3%) unrelated to the disc implant, an injury to the ureter (LeHuec et al. 2003). At one year postoperatively there was no evidence of either disc subsidence or migration. 15 Artificial lumbar disc replacement Bleeding and related complications Charité III In the RCT comparing Charité III versus BAK surgery approximately two thirds of cases during disc space distraction for Charité III implantation showed some epidural bleeding or significant bone bleeding along the posterior edge. This was managed by placing strips of Avitene in the disc space and compressing them. In the first 57 consecutive Charité patients as part of this RCT, Blumenthal et al. (2003) stated mean blood loss was 266 ml from L4/L5 (n=12) and 101 ml from L5/S1 (n=45), with a significant difference in blood loss between the two levels (p<0.05) (Blumenthal et al. 2003). In the 2005 report on this RCT, Blumenthal et al. (2005) reported a mean blood loss of 205ml in Charité III patients. In David (2003) there was one case (1/21, 5%) of epidural vein bleeding. LeMaire et al. (1997) stated that 5% (5/105) of patients had vascular complications, although further details were not given. Mean blood losses reported were 125 ml (Hopf et al. 2002) and 300 ml (Kim et al. 2003). Griffith et al. (1994) reported vein injury occurred in 17% (16/93) of patients. An aortic lesion (1/50, 2%) was reported in Zeegers et al. (1999), related to removal of the prosthesis. Haematomas occurred in 12 patients in this study, with a retroperitoneal haematoma in one patient (Zeegers et al. 1999). ProDisc II Blood loss was not reported in the RCT comparing ProDisc II implants with spinal fusion surgery (Delamarter et al. 2003; Zigler 2003) and was given in only one case series using this device with a minimally invasive approach: mean blood loss was 117 ml per level, with a range of 30 to 350 ml (Mayer et al. 2002). Bertagnoli et al. (2005) reported two cases of retroperitoneal hematomas and a single subcutaneous hematoma during the perioperative period. Bone-related changes Charité III A single centre involved in the multicentre RCT comparing Charité III versus BAK surgery reported one patient (1/41, 2%) had significant postoperative heterotopic ossification (Class 2) with ectopic bone within the disc space, which did not affect motion (McAfee et al. 2003b). Blumenthal et al. (2005) reported one case (1/205, 0.5%) of annulus ossification and one case (1/205, 0.5%) of calcification resulting in bridging trabecular bone. 16 Artificial lumbar disc replacement In Muschik & Meergans et al. (2003) one patient (1/39, 3%) had a spinal fusion four months after Charité III implantation. Caspi et al. (2003) found spontaneous ossification of the intervertebral anterior ligament in two patients (2/20, 10%), the progression of which was halted by intensive physiotherapy. In David (2003) there was one patient (1/21) with incomplete peripheric ossification with no secondary fusion. In their series of patients with complications, van Ooij et al (2003) found: 12 cases (44%) of degenerative disc disease at another level (in seven cases this was present before the surgery); one (4%) spontaneous fusion at the level of the prosthesis eight years postoperatively; 11 cases (41%) of facet joint arthrosis and three cases (11%)of hyperlordosis of the operated segment. LeMaire et al. (1997) reported 4% (4/105) of bone complications: one case of endplate fracture with revision to spinal fusion; one lower endplate subsidence as a result of osteoporosis; and two cases of periprosthetic ossifications. Cinotti et al. (1996) found 15% (7/46) cases of perianular ossification, stating these did not affect the clinical outcome. ProDisc II No bone-related complications were reported in patients enrolled in the RCT comparing ProDisc II implantation versus spinal fusion (Delamarter et al. 2003; Zigler 2003). No perianular ossifications or degenerative changes at levels adjacent the disc replacement or at the facet joints occurred in Tropiano et al. (2003). In this study mean lumbar lordosis was 56.7o (range 30-72o) before surgery and 61.9o (range 46-72o) after surgery. No cases of postoperative fusion were found in Mayer et al. (2002). Other discs There were two cases of anular ossification after Acroflex Acromed implantation: one with autofusion of the joint, the other with angular motion still present on flexion/extension radiographs. No patients had vertebral endplate erosions, sclerosis, vertebral boy remodelling or adjacent level disc degeneration. One late case (1/11) of heterotopic calcification occurred after AcroFlex artificial disc implantation (Freeman et al. 2001). There was no evidence of spondylotic bridging of the implant disc space at one year after insertion of Maverick artificial discs (LeHuec et al. 2003). 17 Artificial lumbar disc replacement Potential Cost Impact Cost Analysis • The Charité artificial lumbar disc implant costs approximately $7000 (AUS; two endplates and one sliding core). This does not include associated costs related to the surgery itself plus care and rehabilitation of the patient. • ECRI have estimated total artificial disc replacement surgery costs between $40,000 and $50,000 (US) (ECRI 2004). • It has been recently calculated the direct annual costs of low back pain in Australian adults is 1.02 billion dollars (AUS) with indirect costs of 8.15 billion dollars (AUS) (Walker et al. 2003). If intervertebral lumbar disc replacement proves to be effective, the result may be an overall reduction in cost to the community. However, no formal cost evaluations have been found. Ethical Considerations Informed Consent Patients should be informed the procedure is still relatively new, and that its longer term safety and efficacy is not yet properly established. There are no known clinical trials in Australia involving artificial lumbar intervertebral disc implantation. Access Issues The technology is likely to be limited to major centres in Australia. Training and Accreditation Training Surgeons are required to be certified, including attendance of a two day workshop, before using the ProDisc II artificial disc in Australia (personal communication, Zacks Khan, Taylor Bryant). Since implantation of an artificial lumbar intervertebral disc is technically difficult, surgeons should be required to undergo specialist training before performing the procedure. 18 Artificial lumbar disc replacement Clinical Guidelines No clinical practice guidelines which include lumbar intervertebral disc replacement were located. Limitations of the Assessment Methodological issues and the relevance or currency of information provided over time are paramount in any assessment carried out in the early life of a technology. Horizon scanning forms an integral component of Health Technology Assessment. However, it is a specialised and quite distinct activity conducted for an entirely different purpose. The rapid evolution of technological advances can in some cases overtake the speed at which trials or other reviews are conducted. In many cases, by the time a study or review has been completed, the technology may have evolved to a higher level leaving the technology under investigation obsolete and replaced. A Horizon Scanning Report maintains a predictive or speculative focus, often based on low level evidence, and is aimed at informing policy and decision makers. It is not a definitive assessment of the safety, effectiveness, ethical considerations and cost effectiveness of a technology. In the context of a rapidly evolving technology, a Horizon Scanning Report is a ‘state of play’ assessment that presents a trade-off between the value of early, uncertain information, versus the value of certain, but late information that may be of limited relevance to policy and decision makers. This report provides an assessment of the current state of development of artificial lumbar disc replacement, its present and potential use in the Australian public health system, and future implications for the use of this technology. Search Strategy Used for Report A systematic search of MEDLINE®, PREMEDLINE®, EMBASE, Current Contents, PubMed, Cochrane Library and Science Citation Index was conducted, from the inception of the databases until September 2004. The York Centre for Reviews and Dissemination, Clinicaltrials.gov, National Research Register, relevant online journals and 19 Artificial lumbar disc replacement the Internet were also searched in September 2004. Searches were conducted without language restriction. Articles were obtained if the abstract contained safety and efficacy data on artificial lumbar disc replacement in the form of randomised controlled trials, other controlled or comparative studies, case series and case reports. The English abstracts of foreign language papers were included if they contained safety and efficacy data. Availability and Level of Evidence List of studies found: Total Studies 29 Systematic Review 1 20 Artificial lumbar disc replacement Table 6 Studies included in review Charité III ProDisc II Randomised controlled trials 1 2 Case Series 16 5 Studies identified but not recovered 1 Maverick Acroflex 1 2 The papers from the systematic review (de Kleuver et al. 2003) have been included in the current report, except for one paper by Wittig et al. (1989). This study used the Charité III artificial disc in 13 patients (14 disc replacements). Follow-up was nine months; clinical outcomes were not reported, and six of 13 patients required secondary surgery. A recent Health Technology Literature Review from Canada, including both artificial cervical and lumbar intervertebral discs, was also found (Medical Advisory Secretariat 2004). Sources of Further Information RCTS in progress RESORD (Randomised European Study on Replacement of the Disc) Contact Person: Mr ERS Ross, Hope Hospital, Salford UK M6 8HD, Telephone +44 161 787 1191 or email at [email protected] ProDisc II IDE Study The multicentre FDA study was started in the US in October 2001. There are currently 18 US sites participating in a large scale prospective RCT comparing clinical outcomes between patients receiving circumferential fusions and the ProDisc II total disc replacement (at a 1:2 ratio) for one- and two-level degenerative disc disease in the lumbosacral spine L3-S1 vertebral segments. The enrolment goal was 500 patients, with approximately 300 patients in the US having received a ProDisc implant in January 2003 (Delamarter et al. 2003). The final results from this trial have not yet been published. Maverick IDE Study The FDA IDE study was commenced in April 2003. The clinical study will compare the safety and effectiveness of the Maverick® artificial disc and spinal fusion surgery (2:1 21 Artificial lumbar disc replacement ratio) at one level between L4-S1. This study is still recruiting patients (www.spineuniverse.com 2004). Flexicore IDE Clinical Study A US clinical trial for the FlexiCore™ artificial disc was announced in August, 2003 by SpineCore Inc. (SpineCore 2003). In July 2004, when Stryker acquired SpineCore Inc., it was stated submission of a PreMarket Approval application to the FDA for the FlexiCore™ was expected to occur in 2007 (PRNewswire-FirstCall/ 2004). Impact Summary • Artificial lumbar intervertebral discs, if successful, could result in substantial gains to the community as back pain occurs in approximately 79% of Australian adults. Some patients with severe pain cannot work, and their overall quality of life is poor. Current surgical options, including spinal fusion, offer limited benefit. • Economic gains resulting from artificial lumbar intervertebral discs may be a consequence of people being able to resume work, and having less pain and requirement for medical treatments. Social gains include patients having a higher quality of life, and being able to take a more active role in their community. • Despite the potential benefits of artificial disc replacement, ECRI (formerly the Emergency Care Research Institute) predicted in one of their Health Technology Forecasts ™ released in June, 2004, that total artificial disc technology will not have as large an impact as disc nucleus replacement, as the latter can be performed using minimally invasive techniques (ECRI 2004). Conclusions This report has reviewed the current research findings of artificial lumbar intervertebral disc implantation. Most of the available data relate to two artificial discs: the Charité III and ProDisc II prostheses. In a single RCT, Charité III implantation appeared to be superior to BAK surgery in terms of clinical outcome, such as Oswestry score. A median of 75% of patients had good to excellent outcomes in 12 case series. Less evidence was available for the ProDisc II artificial disc, results only available for individual centres from the ProDisc II RCT. VAS and Oswestry scores appeared to be reduced more rapidly in patients after ProDisc II versus fusion surgery, however, no clinical benefits of the artificial disc versus spinal fusion were stated. Clinical success ranged from 0% to 100% in the four case series. 22 Artificial lumbar disc replacement Safety issues relating to implantation of the device were reported in a number of studies. In the RCT, Charité III implantation did not result in any increase in neurological adverse events versus BAK surgery. A low incidence (1.5%, 3/205) of device-related neurological adverse events was reported. Device-related complications ranged from 0% to 96% in the case series, with 96% reported in a selected group of patients admitted to a specialist centre with complications after disc replacement surgery. Without this study, device-related complications ranged from 3% to 10% of patients. Complications were not well reported in the subgroups of the ProDisc II RCT. In the three ProDisc II case series with more than two patients, device-related complications were 0% in two studies and 6% in the third. Total complication rates were 1% to 9%. Insufficient evidence was available using the Maverick or Acroflex artificial lumbar intervertebral discs to make any conclusions regarding their safety or efficacy. Special training is likely to be necessary before surgeons perform this procedure. In the publication from the Charité III RCT it was stated “artificial disc replacement is one of the most challenging procedures in spine surgery in the senior author’s experience” (Geisler et al. 2004). The correct patient selection appears crucial in gaining the best results from implantation of artificial lumbar intervertebral discs. Younger patients with single disc disease, limited degenerative joint changes and without previous spinal surgery are prime candidates for the procedure. Exclusions would include patients with osteoporosis, facet joint arthrosis or severe scoliosis. All patients selected for surgery should have proven disc pain eg. positive provocative discography, and have attempted conservative treatment options for at least six months. The development of artificial disc arthroplasty has garnered significant interest from the medical community but the true safety and effectiveness of these devices are not fully known. From the studies retrieved, that there is no doubt that these artificial discs are capable of restoring range of motion to the disc, at least in the short term. However, restoration of disc range of motion does not always translate to pain relief or improved function. In addition to this, it is not known if the extra few degrees in range of motion offered by disc replacement instead of fusion is functionally significant when considering the motion available at adjacent disc levels and hips. Other concerns include the resilience of these artificial disc towards wear and tear, a disc prosthesis may be expected to withstand more than 100 million cycles in its lifetime and no artificial disc models have been tested this extensively (Frazer et al. 2003). In addition to this, adjacent level degeneration after disc replacement has not been studied extensively, the assessment by Cinotti et al. (1996) where no adjacent level degeneration was identified at 2 years followup is somewhat misleading when more than 75% of their original cohort was not investigated (Fraser et al. 2003). Further studies will be needed to fully assess the factors influencing the outcomes of lumbar intervertebral disc replacement, and the safety and efficacy of the procedure. 23 Artificial lumbar disc replacement References Aunoble S, Donkersloot P, Le Huec JC. Dislocations with intervertebral disc prosthesis: two case reports. European Spine Journal 2004;13:464-7 Bertagnoli R, Yue JJ, Shah RV, Nanieva R, Pfeiffer F, Fenk-Mayer A, Kershaw T, Husted DS. The treatment of diabling single-level lumbar discogenic back pain with total disc arthroplasty utilizing the Prodisc prosthesis. Spine 2005;30(19):2230-2236. Bertagnoli R and Kumar S. Indications for full prosthetic disc arthroplasty: a correlation of clinical outcome against a variety of indications. European Spine Journal 2002; 11(Suppl 2):S131-6 Bertagnoli R and Schonmayr R. Surgical and clinical results with the PDN prosthetic disc-nucleus device. 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Low back pain in Australian adults: the economic burden. Asia Pac J Public Health 2003;15[2]:79-87 Walker BF, Muller R, Grant WD. Low back pain in Australian adults: prevalence and associated disability. J Manipulative Physiol Ther 2004;27(4):238-244. 27 Artificial lumbar disc replacement Wittig C, Muller RT, Staudte HW. Bandscheibenprosthese SB Charite, erfolge und misserfolge an hand von fruhergebnisse. Med Orthop Technik 1989;109:70-74 Zeegers WS, Bohnen LM, Laaper M, Verhaegen MJ. Artificial disc replacement with the modular type SB Charite III: 2-year results in 50 prospectively studied patients. European Spine Journal. 1999;8(3):210-217. Zigler JE. Clinical results with ProDisc: European experience and U.S. investigation device exemption study. Spine 2003;28(20):S163-6 Zigler JE, Burd TA, Vialle EN, Sachs BL, Rashbaum RF, Ohnmeiss DD. Lumbar spine arthroplasty: early results using the ProDisc II: a prospective randomized trial of arthroplasty versus fusion. Journal of Spinal Disorders & Techniques. 2003;16(4):352-361. 28 Artificial lumbar disc replacement Appendix A: Table of Key Efficacy and Safety Findings Charité III Study details Key efficacy findings Key safety findings Appraisal/Comments Randomised Controlled Trial (Charité III) Geisler et al. 2004, USA (studies included: McAfee et al. 2003a and 2003b; Blumenthal et al. 2003 304 patients Charité: n=205 BAK: n=99 14 clinical centres Charité L4/L5 61/205 (29.7%) L5/S1 144/205 (70.3%) No intergroup differences. BAK 32/99 (32.3%) 67/99 (67.7%) Follow-up: Clinical and radiographical evaluation at 6 weeks and 3, 6, 12 and 24 months. Implant: SB Charité III Comparison: Patients had Charité disc replacements (Charité) or lumbar interbody fusion involving BAK cages and iliac crest bone graft (BAK). Selection criteria: Primary inclusion criteria included: single-level degenerative disc disease at L4/L5 or L5/S1 confirmed by MRI and provocative discography; age 18 to 60 years; ODI score ≥ 30; back pain VASrated score ≥ 40 with no radicular component (referred leg pain was Neurological changes Neurological status: change from baseline 6 months No change Significantly improved Slightly improved Slightly deteriorated Significantly deteriorated total missing 12 months No change Significantly improved Slightly improved Slightly deteriorated Significantly deteriorated total missing 24 months No change Significantly improved Slightly improved Slightly deteriorated Significantly deteriorated total Adverse neurological events (NAEs): Charité No (%) BAK No (%) 147 (77) 6 (3) 67 (76) 5 (6) 27 (14) 9 (10) 9 (5) 4 (5) 1 (1) 3 (3) 190 15 88 11 153 (82) 5 (3) 61 (75) 2 (2) 19 (10) 12 (15) 8 (4) 6 (7) 2 (1) 0 187 18 81 18 141 (79) 2 (1) 65 (82) 0 19 (11) 10 (13) 13 (7) 3 (4) 4 (2) 1 (1) 179 79 Factor No of NAEs No of patients with NAEs Major NAE burning or dysesthetic leg pain motor deficit in index level nerve root injury Minor NAE numbness in index level numbness in sacral nerve distribution Other NAE numbness in peripheral nerve or nonindex level positive Waddell signs reflex change mechanical signs (straight leg raising test) Charité No (%) 38 34 (16.6) BAK No (%) 20 17 (17.2) 10 (4.9) 5 (2.4) 4 (4.0) 3 (3.0) 4 (2.0) 1 (1.0) 1 (0.5) 20 (9.8) 20 (9.8) 0 8 (8.1) 7 (7.1) 0 1 (1.0) 8 (3.9) 5 (2.4) 8 (8.1) 4 (4.0) 1 (0.5) 1 (1.0) 2 (1.0) 0 2 (2.0) 1 (1.0) Device-related neurological events: No of NAEs Charité No (%) 3 (1.5)a BAK No (%) 0 a: one event (nerve root injury) was classified as severe. Bleeding: In approximately two thirds of the cases during disc space distraction, some epidural bleeding or Potential for Bias: Randomisation was performed according to a random number generator. (McAfee et al. 2003a). The method of allocation concealment was not stated. In one of the centres involved in the study an independent nurse practitioner of physician’s assistant interviewed the patient and administered the Oswestry and VAS scores. (McAfee et al. 2003a) At 6 months there were 190 Charité III and 88 BAK patients; at 12 months 187 Charité III and 81 BAK patients; and at 24 months 179 Charité III and 79 BAK patients remained. There were more patients missing in the BAK (20/99, 20%) versus Charité III groups (26/205, 13%) which may have biased the result. There were no significant differences in age or sex between the two groups. Outcome measures and their validity: All outcome measures used were well validated. Other comments: “…precise placement is crucial to the proper functioning of the Charité prosthesis. For best results and to mimic the normal instantaneous axis of rotation of a normal intact disc, the Charité device must be placed approximately 3 to 3 mm posterior to the center of the disc space and as close to the exact center as possible in the coronal plane. Large 29 Artificial lumbar disc replacement permitted); and failed nonoperative treatment of at least 6 months duration. Primary exclusion criteria: Previous thoracic or lumbar fusion; multilevel degenerative disc disease; facet joint arthrosis; noncontained herniated nucleus pulposus; osteoporosis; spondylolisthesis slip >3mm; scoliosis > 11o; and midsagittal stenosis < 8mm. missing 26 20 No significant intergroup differences. ODI score: Mean preoperative 24 months Mean change Charité 54.6 (n=205) 25.8 (n=179)a -24.8 BAK 52.1 (n=99) 30.1 (n=79) -22.0 From McAfee et al. 2003 (n=60: Charité n=41, BAK n=19) a: number extrapolated from patients remaining at 24 months. At all time points the ODI score was significantly reduced in the Charité patients. There was a significant difference in the Charité versus BAK ODI scores at 3 and 6 months, but not from 12 months. 25% improvement in ODI score: 24 months Charité 62% (n=179) BAK 49%* (n=79) *: p=0.0354; numbers extrapolated from total patients. There were significantly more patients with an improvement in ODI score of 10 points or more from 3 to 24 months in the Charité versus BAK patients (p<0.05). VAS score: Mean preoperative 24 months Mean change Charité 72 (n=205) BAK 71.8 (n=99) 30.6 (n=179)a -41.4 (-57.5%) 36.3 (n=79) -35.5 (-49.4%) a: number extrapolated from patients remaining at 24 months. 20 point improvement in VAS score: 24 months Charité 65% (n=179)a significant bone bleeding along the posterior edge occurs, which was easily managed by placing strips of Avitene in the disc space and compressing them down against the remaining posterior longitudinal ligament. BAK 56%* (n=79) Estimated blood loss (McAfee et al. 2003): n=60: Charité n=41, BAK n=19 Mean 289.5 ml (range 50-1800 ml) Mortality: One death unrelated to the spinal procedure (? group). Other complications: In the Charité group there were no dislodgements of the prostheses, no cases of significant subsidence, no evidence of prosthetic loosening and no late infections. deviations from this placement may yield less than ideal results.” This trial has been criticised for using BAK surgery as a comparison, as this is no longer the best method of fusion, but a literature search was included in the study to provide results from other forms of fusion surgery.” “At the time of publication, new thirdgeneration instrumentation for implantation of the Charité device will allow for an intuitive, straightforward implantation of the prosthesis.” Discography should be performed prior to any form of artificial disc replacement. It was stated “surgeon training is essential for good clinical and functional outcomes”. The study protocol indicated surgeons at each study site should perform five training cases prior to randomisation (71 training cases were performed). One patient had postoperative small bowel obstruction of uncertain origin: (? group). Found adhesions of greater omentum at surgery, now use of the self-retaining Thompson retractor to retract the bowel is ‘curtailed’. One patient had significant postoperative heterotopic ossification (Class 2), with ectopic bone within the disc space which did not affect motion. In the total cohort there was one case each of: retrograde ejaculation, depression, adynamic ileus requiring a nasogastric tube, adynamic ileus spontaneously resolving without a nasogastric tube, one urinary tract infection, one case of epididymitis, one case of lateral epicondylitis and one case of degenerative changes at the vertebral level above. From Blumenthal et al. 2003 (n=57 first consecutive Charité cases) 30 Artificial lumbar disc replacement *: p=0.1028; a: number extrapolated from patients remaining at 24 months. Flexion-extension range of motion: 24 months Charité 7.4 ± 5.28o (n=179)a BAK 1.1 ± 0.87o (n=79) Blood loss (ml): L4-L5 L5-S1 All levels n=12 n=45 n=57 265.9 101.4* 134.3 *: p<0.05 versus L4-L5 level Mean ± SD; a: number extrapolated from patients remaining at 24 months. Re-operation: No patients in either group required additional spinal reconstructive procedures at 1 to 3 years follow-up. From McAfee et al. 2003 (n=60: Charité n=41, BAK n=19) Surgery length n=60: Charité n=41, BAK n=19 Mean 88.4 minutes (range 57-137) Hospital stay n=60: Charité n=41, BAK n=19 Mean 3.03 days (range 2-6) From Blumenthal et al. 2003 (n=57 first consecutive Charité cases) Operating time (min) L4-L5 L5-S1 n=12 n=45 95.2 74.4* *: p<0.05 versus L4-L5 level All levels n=57 78.7 31 Artificial lumbar disc replacement Study details Randomised controlled trial Blumenthal et al. (2005) USA Prospective, randomized, non-blinded, FDAapproved study at 14 investigational sites in USA. 304 patients (Investigational group: 205, control group: 99) Follow-up: Clinical assessments were conducted at 6 weeks prior to surgery and at 3, 6, 12 and 24 months post-surgery. At 12 months the follow-up rate was 95.8% of the investigational group and 94.2% of the control group. At 24 months 91.5% of the investigational group and 89.2% of the control group were available for assessment. Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: Single-level symptomatic degenerative disc disease at L4-L5 or L5-L1 confirmed by provocative discography, back and/or leg pain without nerve root compression (radiculopathy) with a visual analog scale (VAS) score ≥40 and an ODI score ≥30, ability to tolerate an anterior abdominal approach, and failure to respond to nonfusion treatment for a period of 6 months. Exclusions: Previous thoracic or lumbar fusion, current or prior fracture at L4,L5, or S1, symptomatic multilevel disc degeneration, osteoporosis, spondylolisthesis >3mm, spondylosis, and scoliotic deformity >11º. Key efficacy findings Key safety findings Appraisal/Comments Surgery No significant difference was noted between the two patient groups for mean operative time and mean blood loss. Complications The incidences of neurological complications were not different between groups. Potential for bias Random allocation of patients was done by a contract research organisation using SAS software in a 2:1 ratio. Pain in bone graft donor site was experienced by 18 (18.2%) control patients. The investigator, key office staff and operating room staff were not blinded to group assignment. Patients were only blinded until after the surgery. This may have affected the results of the patient’s satisfaction survey. Hospital stay was significantly lower (p=0.0039) for the investigational group (3.7 days) versus the control group (4.2 days) Mean Oswestry Disability Index Period Preop. Mean %imp from preop 6 wks Mean %imp from preop 3 months Mean %imp from preop 6 months Mean %imp from preop 12 months Mean %imp from preop 24 months Mean %imp from preop Investigational Control 50.6 0 52.1 0 37.7 23.9*(**) 43.7 12.7*(**) 29.9 40.2*(**) 37.4 25.7*(**) 27.5 46.2*(**) 35.8 30.8*(**) 26 48.8*(**) 31.8 37.9*(**) 26.3 48.5* 30.5 42.4* Device failures occurred in 11 (5.4%) investigational patients and 9 (9.1%) control patients. Approach related complications occurred in 20 (9.8%) investigational group patients and 10 (10.1%) control group patients. Overall complication rates did not differ between groups. Outcome measures and their validity: All outcome measures used were well validated. Other comments At 24 months, 185 patients were available for assessment in the investigational group while 82 patients were available in the control group. Note: * indicates significant difference of Intra group to preop; (**) indicates significant difference between groups 32 Artificial lumbar disc replacement Mean Visual Analog Scale Scores Period Preop. Mean %imp from preop 6 wks Mean %imp from preop 3 months Mean %imp from preop 6 months Mean %imp from preop 12 months Mean %imp from preop 24 months Mean %imp from preop Investigational Control 72 0 71.8 0 36.4 35.9*(**) 44.1 27.7*(**) 35.7 35.7*(**) 44.5 27.4*(**) 33.1 39*(**) 43.9 28.2*(**) 32.9 39.1*(**) 40.4 30.9*(**) 31.2 40.6* 37.5 34.1* Note: * indicates significant difference of Intra group to preop; (**) indicates significant difference between groups Patient Satisfaction Period 12 months 24 months Investigational 71.3% 73.7% Control 59% 53.1% No significant difference was observed between the two groups with regards to patient satisfaction (p = 0.0559). Whether patients would undergo the same treatment Period 12 months 24 months Investigational 73.4% 69.9%* Control 57.7% 50.0% The investigational group had significantly higher 33 Artificial lumbar disc replacement proportion of patients who would have the same treatment again compared to the controls at 24 months (p=0.0063). Clinical success Overall clinical success was achieved in 57.1% of patients in the investigational group and 46.5% in the control group (p<0.0001). In a subgroup of patients who completed 24 months follow-up, significantly higher clinical success was noted in the investigational group (63.6%) compared to controls (56.8%) (p=0.0004). Rate of clinical success (defined by ≥25% improvement in ODI scores at 24 months compared to preop scores) was significantly higher in the investigational group (63.9%) compared to the controls (50.5%) (p=0.0338). Narcotic medication use Investigational Control p=0.0083 Proportion of patients using narcotics to control pain (overall) 72.2% 85.9% In subgroup of patients who achieved clinical success: Investigational Control p=0.0428 Proportion of patients using narcotics to control pain (at 24 months) 64.0% 80.4% 34 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Randomised controlled trial McAfee et al. (2005) USA Operative level Range of Motion (ROM) None stated Potential for bias The randomisation process was the same as Blumental et al. (2005). This study was performed on the same patient cohort. Prospective, randomized, non-blinded, FDAapproved study at 14 investigational sites in USA. 304 patients (Investigational group: 205, control group: 99) Follow-up: Clinical assessments were conducted at 6 weeks prior to surgery and at 3, 6, 12 and 24 months post-surgery. Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Mean ROM was equivalent in both groups pre-surgery. At 3 months post-surgery, ROM decreased in both groups. However, ROM for the investigational group began to increase from months 6 to 24. ROM for the control group continued to decrease from months 6 to 24. At 6 months, ROM in the investigational group was 92.4% of pre-operative ROM. At 24 months, ROM in the investigational group was 113.6% of pre-operative ROM. Surgical Placement Selection criteria: Single-level symptomatic degenerative disc disease at L4-L5 or L5-L1 confirmed by provocative discography, back and/or leg pain without nerve root compression (radiculopathy) with a visual analog scale (VAS) score ≥40 and an ODI score ≥30, ability to tolerate an anterior abdominal approach, and failure to respond to nonfusion treatment for a period of 6 months. Exclusions: Previous thoracic or lumbar fusion, current or prior fracture at L4,L5, or S1, symptomatic multilevel disc degeneration, osteoporosis, spondylolisthesis >3mm, spondylosis, and scoliotic deformity >11º. Outcome measures and their validity: All outcome measures used were well validated. Other comments A mean ROM of 7.5º was reported at 24 months. This includes subjects with suboptimally placed Charite discs, therefore suggesting that the disc is quite forgiving in terms of placement and proper function. At 24 months follow-up: 82.9% of patients were graded as having ideal placement (Group I) 10.7% were graded as having suboptimal placement (Group II) 6.2% were graded as having poor placement (Group III) However, the authors stated that if the placement is poor enough to be 5mm or more off axis in wither the midsagittal or coronal planes, the flexion/extension ROM will be negatively affected. Correlation of surgical placement with clinical outcomes Mean ODI scores (at 24 months) improved with the degree of technical accuracy. Technical accuracy groups Group I Group II Group III P<0.05 Mean ODI 24.1 30.3 36.3 35 Artificial lumbar disc replacement Mean VAS scores (at 24 months) improved with the degree of technical accuracy. Technical accuracy groups Group I Group II Group III p=0.016 Mean VAS 28.3 35.4 48.4 Correlation of surgical placement with operative level ROM Technical accuracy groups Group I Group II Group III Flexion/extension ROM 7.12º ± 4.06º 7.47º ± 4.41º 3.15º ± 3.51º A significant difference was observed between both ideal (group I) and suboptimal (group II) and poor placement (group III) regarding flexion/extension ROM (p=0.003). Disc space height and subsidence The Charite disc was significantly more effective than the BAK controls in restoring height of the collapsed disc space at L4-L5 and L5-S1 (p<0.05). 36 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Migration of disc: 2/20 (2 days after surgery due to incomplete severing of the postlongitudinal ligament in 1 patient and 2 weeks post-surgery due to small fracture of the lower endplate in the other). Potential for bias: It was not stated whether the patients were consecutive or a selected group. Case series Caspi et al.6 2003, ISRAEL n=20 (23 prostheses) Segment No L4/L5 and L5/S1 3 Single level 17 Follow-up: 48 months Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: All patients had suffered low back pain with/without radicular pain for at least 5 years. Three patients had undergone previous surgery by a posterior approach. Preoperative Xrays showed narrow disc space and discography as a pain provocative and memory test was performed in all patients. MRI was used to analyse the diseased disc and to eliminate a residual posterior compression from scar tissue in the failed back that was operated on. Clinical results: Result No Excellent 11 Good 4 Fair 3 Poor 4 Total patients add up to 22? a: 1 patient had secondary fusion and 1 is waiting for surgery. “The postoperative Xrays showed good results, and after further investigation it became apparent that all four were in different stages of ligation.” (it is uncertain what the authors mean by ‘ligation’) Return to work: Completely disabled Resumed physical labour Returned to light and sedentary work No 4 1 15 Range of segmental motion: Average 3-9o Device Failure: There was a small fracture of the lower endplate (leading to disc migration) in 1 patient. Spontaneous ossification of the intervertebral anterior ligament: Observed in 2 patients, its progression was halted by intensive physiotherapy. Other complications: Intraoperative laceration of the ureter and thrombosis of the iliac artery Infection Sexual complications Outcome measures and their validity: There was no mention of how the clinical results were obtained, whether it was the patients’ subjective feelings or if a validated grading system was used. Other comments: It was stated that the largest possible disc prosthesis was chosen for insertion (in most cases measuring 9.5mm). “The main indication for lumbar disk prosthesis is chronic lower back pain due to disk degeneration in young patients (up to age 55). The lumbar disk prosthesis is indicated for patients under the age of 55 due to bone quality and status of posterior facet joints.” No 1 0 0 Re-operation: 2/20 (10%) because of disc migration, larger prostheses were implanted. 29 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Measures of Pain: No measures of pain reported. Only one patient had moderate radicular pain in the long term (much less than after recurrent posterior surgery). Complications: One case of epidural vein bleeding and one case of incomplete peripheric ossification with no secondary fusion. Potential for bias: The method of patient selection was not stated, therefore whether the patients are likely to have been a biased sample could not be assessed. Case series David 2003, FRANCE (abstract) n=21 Segment L5/S1 L4/L5 No 14 7 Operated on between 1993 and 2001 Follow-up: Average of 4 years Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: Patients with severe sciatica with a recurrent hernia two years (on average) after posterior surgery for disc hernia at the same level. All had chronic low back pain with a fair result after the first surgery. Hernia confirmed by MRI and discography-CT; sometimes through the posterior ligament but the disc was not extruded. Some patients had some bone reaction (n=9; Modic sign). Mobility: All prostheses had on average 12o on flexion/extension films and 5 o on bendings. Work: 19/21 (90%) of patients recovered and returned to the same job. Stauffer-Coventry-Cauchoix classification: Excellent: 9/21 (43%) Good: 12/21 (57%) Outcome measures and their validity: The Stauffer-Coventry Index is a clinical surgical outcome measure, designed for administration after surgery and consisting of four multiple choice self-report questions regarding pain reduction, return to work, limitations of physical activities and medication usage. (assumed the StaufferCoventry-Cauchoix classification is a French version of this, but could not find further information) Other comments: This study was in abstract form only, limiting the amount of information about the study. 30 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Operating time: Mean 180 minutes Blood loss: Mean 300 ml Outcome: All four patients with neurological compromise had marked improvement of symptoms within their hospital stay, with improvement maintained to the last follow-up. Perioperative complications: None Potential for bias: This was a small group of only five patients. These patients were selected from 11 patients with surgery, and it is possible the 6 patients not included had poorer outcomes. Case series Kim et al. 2003, KOREA n=5 (11 patients had surgery but results only given for 5) Surgery since January 2002 Segment No L1-L2 1 L3-L4: 2 L5-S1 1 L3-L4-L5: 1 (except for one patient, all juxtafusional degenerations were superior to the previous fusion or nonunion) Follow-up: Radiographs taken on day 1 and at 1,3, 6 and every 6 months postoperatively. Follow-up > 6 months in all patients. Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: Patients with symptomatic juxtafusional degeneration syndrome undergoing surgical treatment have had artificial disc replacement unless contraindicated. Indications were neurologic disturbance (neurogenic intermittent claudication, radiculopathy) and/or severe back pain compromising the activities of daily living and not responding to prolonged conservative treatment of ≥ 6 months. All patients had radiographs, bone mineral density measurements, lumbar MRI and CT scans before surgery. Exclusions: target level higher than L1-L2, fractured vertebral body, severe facet joint degeneration, posterior element incompetence resulting in antero retrolisthesis, infection, significant spinal misalignment or disc space tilting and/or wedging in the coronal and sagittal plane, and negative provocative discography. ODI Score: Preoperative 1 month 3 months 6 months 64% 31% 25% 24% Technical failure: None requiring re-operation, and no implant subsidence or dislocation at 6 months follow-up. Outcome measures and their validity: Outcome measures appeared to be using well accepted measures. Other comments: MacNab’s criteria: Overall clinical improvement using MacNab’s criteria was excellent in three and good in two patients at 6 months follow-up. Re-operation: There were no technical failures or complications that needed a reoperation. 31 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Clinical improvement: Complete or satisfying improvement: DDD PNS: 4/10 23/29 (79%) 4/10 (40%) Improved in part: DDD PNS 0/29 (0%) 2/10 (20%) No benefit: DDD PNS 6/29 (21%) 4/10 (40%) Complications: There were 10% complications in both groups, including 2 fractures of a small fragment of the dorsal wall of the vertebral body, 1 posterior subluxation of the implant, 1 fusion after 4 months. Potential for Bias: Study is in abstract form only with minimal detail of the procedures and results. It was not stated how patients were selected. Case series Muschik & Meergans 2003, GERMANY 39 patients 29 with degenerative disc disease (DD) and 10 with postnucleotomy syndrome (PNS) 2000 to 2002 Segment No L5/S1 27 L4/L5 8 L4/L5 and L5/S1 4 Follow-up: 2 + 1 years (not sure if 1 year is the SD) Implant: SB Charité III Comparison: Patients having Charité disc replacements had either degenerative disc disease (n=29) or postnucleotomy syndrome (n=10). Selection criteria: Patients whose operation was < 12 months ago were excluded. Mobility: DDD PNS 8+2o 6+2o Note type of variance not stated. Neurological deficits: No neurological deficits were observed in either group. Outcome measures and their validity: Details of the types and methods of testing were not included in the abstract. Other comments: Authors conclude the indications for artificial disc replacement in patients with postnucleotomy syndrome ‘remain unclear’. Relordisation of operated segments: DDD PNS 9o 9o Re-operation: 1/39 (3%) because of a posterior subluxation of the implant. 32 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings None stated Intraoperative complications: Appraisal/Comments Case series Pimenta et al. 2003, BRAZIL n=55 (67 implants) January-December 2002 Segment No L2/L3 1 L3/L4 4 L4/L5 30 L5/S1 32 1 replacement 2 replacements 3 replacements No 44 10 1 Endplate fracture due to excessive distraction Iliac vein lesions Ureter lesion No 1 2 1 Postoperative complications: Abdominal hernia Implant subsidence Seroma Transitory premature ejaculation Foraminotomies due to fibrosis (in cases of previous spinal surgery) No 1 2 1 1 2 Potential for bias: Study is published in abstract form only, limiting the amount of information which was given. Outcome measures and their validity: Limited outcomes were given and no efficacy outcomes were reported. Other comments: The authors state ‘we recommend intraoperative assistance of a surgeon experienced in the retroperitoneal space to avoid possible eventualities.’ Follow-up: 1 to 11 months Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: Patients had degenerative disc disease (n=35), previous spinal surgery (n=7), pathology on the vertebra adjacent to fusion (n=6), previous failed PDN (n=4), isthmic spondylolisthesis (n-2) and a non-union at the level of fusion (n=1). Cases related to prosthesis: n=2 (4%) Cases related to any spinal surgery: n=9 (16%) 33 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Clinical outcome: Result No (%) Excellent 23/31 (74%) Good 6/31 (29%) Fair 2/31 (10%) Disc displacement: A slight displacement of the core occurred in one case without any clinical symptoms and signs. Potential for bias: This study was available only in abstract form, it was difficult to determine if the patient group was biased and how patients were selected. Case series Su et al. 2003, CHINA n=31 (37 discs) April 1998 to April 2000 Follow-up: Mean 26 months (range 17 to 41 months) Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: Patients had lumbar disc degenerative diseases and lumbar disc herniation with disc space narrowing. No Disc degenerative disease 16 (18 discs) Disc herniation with disc 13 (17 discs) space narrowing Recurrent disc herniation 2 Mobility of operated area: Degrees Anterior flexion 4.0 Posterior flexion 5.1 Total 9.1 Intervertebral disc space: Operated disc space was an average of 4.2 mm higher than before surgery. Outcome measures and their validity: The method of measuring clinical outcome was not stated, it may have been only a subjective measure. Other comments: . 34 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings It was stated there was a “lack (of) information concerning the pain level and functional status prior to the disc replacement, but all patients told us that they preoperatively suffered serious and constant back pain and leg pain for considerable time periods”. Early complications: Complication No Dislocation of disca 1/27 Abdominal wall/ retroperitoneal 4/27 haematoma Retrograde ejaculation, libido loss, 1/27 erectile dysfunction/hypoaesthesia Erectile dysfunction 1/27 (without retrograde ejaculation) Asymmetrical insertion 1/27 (with no pain relief) a: L5-S1 prosthesis dislocated anteriorly within 1 week. 9/27 (33%) of patients had early complications. Appraisal/Comments Case series van Ooij et al. 2003, THE NETHERLANDS n=27 early (n=26 late) 1995Segment No L4/L5 12 L5/S1 6 L2/L3 1 L3/L4 1 L4/L5 and L5/S1 5 L3/L4, L4/L5 and L5/S1 1 L5/L5 (?L4/L5) 1 3 L4/L5a a: preceded by an anterior fusion of L5/S1 Preceding the surgery: Percutaneous nucleotomy of the same level: n=3 Posterior undercutting facetectomy: n=2 Herniated disc surgery: n=1 Follow-up: Mean 53 months (range 11127 months) (Mean 91 months, range 15-157 months, in 26 patients with mid- and long-term evaluation) Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: Patients at a tertiary university referral center with persisting back and leg complaints after a disc prosthesis at another institution. Good initial result: 12/26 (46%; 1 month to 10 years) No benefit: 14/26 (54%) (In one patient there was early subluxation of the prosthesis) Re-operation: 15/27 (56%) Removal of prosthesis in 4 patients and a second spinal reconstructive salvage procedure in 11 patients. Late complications: Complication No Degenerative disc disease at another 12a level Fusion at level of prosthesis 1b Facet joint arthrosis 11 Subsidence of the prosthesis 18c Subluxation 1d Anterior migration of the prosthesis 2e Prosthetic wear 1f Breakage of metal wire around the 2 polyethylene core Hyperlordosis of the operated 3g segment 100% of patients had late complications. a: in 7 patients degeneration was obvious on X-rays before the operation and in 7 patients adjacent level degeneration at previously sound levels was present after surgery. b: after 8 years of pain relief spontaneous fusion led to new symptoms, probably because of disc degeneration 2 levels higher. Potential for bias: These patients were a selected group with complications, the total number of patients operated on at the other institution was not stated, and therefore the incidence of complications could not be calculated. Outcome measures and their validity: No real efficacy results were given; the results given appeared to be subjective and did not use standardised measures such as the VAS score. Other comments: No data were available on the pain level and functional status of the patients prior to surgery. 35 Artificial lumbar disc replacement c: in 10 cases the prosthesis was definitely too small, and of adequate width and depth in 8 cases; the polyethylene core was radiographically never dislocated out of the metal plates) d: the core subluxated anteriorly and the L4-L5 segment above a formerly fused L5-S1 segment was blocked in extension. e: causing compression of the great vessels in 1 patient, the prosthesis was removed after 10 years; in 1 patient a posterior fusion was recently performed. f: after > 13 years the prosthesis at L4-L5 is showing radiological signs of wear, being subsided into L4 and surrounded by extensive sclerosis; CT scans showed fragmentation of surrounding bone and cyst formation, analogous to polyethylene wear effects around hip prostheses; the patient is severely handicapped but refuses further surgery. g: resulting in an opening of the facet joints in the superior part and a compression in the inferior part of the joints; this could be a cause of later facet joint arthrosis). 36 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Pain postoperatively: General Pain-free Reduction in pain No pain relief Leg Pain Reduction in patients with preoperative pain Negative straight leg test Recovered motor symptoms Total complication rate: General or specific complications: 9/20 (45% ) Potential for Bias: How patients were allocated to the groups was not stated. Case series Buttner-Janz et al.5 2002, GERMANY 20 patients (14 unisegmental, 6 bisegmental replacements) Follow-up: 46 months (6 months to 13 years) Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: All patients- postnucleotomy syndrome No 25% (5/20) 70% (14/20) 5% (1/20) 83% (15/18) 93% (14/15) 40% (2/5) Segmental/sagittal total range of motion: Unisegmental: implantation mean 6.8o (range 0-20o) Bisegmental implantation: mean 5.8o (0-14 o) in second disc segment. Neighbouring segments with the best function had a range of motion of 6.8o Outcome measures and their validity: Validity of outcome measures (general pain, leg pain and ROM) are difficult to ascertain from abstract alone Other comments: Authors note the ‘stated general and specific complications had a definite influence on the results in one patient and a questionable influence on a second patient’ suggesting that complications related to the device are, in reality, lower than 45% (i.e. 2/20=10%) 37 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Analgesia Requirement: NSAID use decreased from 33 patients to 5 patients postoperatively. Blood loss: Mean 125 ml Potential for bias: Losses to follow-up noted (i.e. 25/35 patients had an angle of lordosis measurement). Patients were prospectively studied. Case series Hopf et al.6 2002, GERMANY 35 patients (24 unisegmental, 11 bisegmental). Follow-up: mean 14.7 months. Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: Unsuccessful conservative management of low back pain > 6 month. Age < 45 years, radiologic evidence of DDD with or without disc prolabation and positive for preoperative diagnostic measures. Scott-Young & Tan et al.7 2002, AUSTRALIA (abstract) 86 patients (113 prostheses) Results from one surgeon since 1996. Follow-up: mean 20 months (range 2 months to 5 years) Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: None stated Angle of Lordosis (L1-S1): Mean increased from 35.6 degrees to 42.6 degrees (20.2% increase) Outcome measures and their validity: How the angles of movement were measured was not reported Length of hospital stay: Mean 16.8 days Other comments: Authors note that ‘indication in patients with failed back surgery cannot be estimated yet’. They also note that ‘improvements of the instrumentation are mandatory’. Operating time: Mean 85.5 minutes Segmental Angle: Increased from an mean of 19 degrees to 30 degrees (57.5% increase) Results: Good to excellent 84% Complications: “Complications have the potential to be catastrophic but attention to surgical detail results in minimal complications which will be discussed in the body of the presentation.” Potential for Bias: It was not stated whether the patients were consecutive or a selected group. One surgeon performed all procedures, negating any intersurgeon variability. Outcome measures and their validity: Questionnaires including Roland-Morris and Oswestry, Visual Analogue Scores and SF36 Data were collected, but these results were not stated. The method of measuring the ‘good to excellent’ results was not stated. Other comments: It is difficult to analyse the study as it is only in abstract form. 38 Artificial lumbar disc replacement Study details Case series Sott et al.7 2000, UK 14 patients (with 15 prostheses). Follow-up: mean 48 months (range 18-68 months). Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: Patients with DDD accompanied by segmental instability. Key efficacy findings Key safety findings Appraisal/Comments Overall patient-reported outcome: (pain relief, return to employment and/or general physical activity): Result No Good 71% (10/14) Fair 14% (2/14) Poor 14% (2/14) No major complications. Some minor complications. Potential for Bias: Small sample size, it was not stated if the patients were consecutive or not. Outcome grouped by greater or less than 45 years of age did not influence outcome. Disc height restored in all cases. 1 patient – warmer left foot due to interference with left paravertebral sympathetic nerves. Implant migration: 7% (1/14) lower prosthetic endplate had sunk by 3 mm. Outcome measures and their validity: Stauffer and Coventry and Oswestry Disability scoring systems were used. Other comments: Authors noted that ‘in contrast to prior publications, age >45 years did not appear to adversely affect outcome’. 39 Artificial lumbar disc replacement Study details Case series Zeegers et al.8 1999, THE NETHERLANDS 50 patients (29 patients unisegmental, 18 bisegmental and 3 trisegmental) Follow-up: minimum 2 years Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: Patients with ‘symptomatic discopathies’; 54% had undergone previous spinal surgery. Key efficacy findings Key safety findings Appraisal/Comments Satisfactory clinical result: 32/46 (70%) Patients <45 years had a significantly better outcome. Result No Complications related to anterior approach: 15% of patients had side-effects or complications of a more permanent character. Potential for bias: Four patients lost to follow-up, this may have influenced the strength of some of the efficacy findings. Patients were studied prospectively and all operated on by the same surgeon, negating any inter-surgeon variability. It was not stated if the patients were consecutive or not. Improvement in leg pain at 2 years 64% (27/42) Improvement in low back 65% (30/46) pain Returned to work 81% (35/43) Able to reduce their analgesia 44% (15/34) Patients with no previous surgery and no other degeneration of spinal disorder (apart from symptomatic discopathy) had a positive clinical result of 80% at 2 year follow-up. Radiographic result at 2 years: Result No Good 74% (28/38) Fair 24% (9/38) Malpositioned implant 5% (2/38) Asymmetric position, 18% (7/38) clinically acceptable Hospital stay: All patients had supine bedrest for an average of 4 days (range 0-45 days) followed by a mean time to mobilization of another 7 days (range 1-45 days). Total hospital stay averaged 10 days (range 3-90 days) according to the protocol of the period. Range of motion: Flexion-extension range on lateral radiographs averaged 9o (range 2-17o) 2 years postoperatively (preoperative range of motion was an average of 9o, range 2-20o). Complications up to 2 years after surgery: Temporary Permanent n=44 n=8 Neurological (n=10) Dysaesthesia of 4 3 legs Paresis/muscle 1 — weakness Cramps in legs 2 — Wound/haematoma (n=17) Painful/numb 5 — scar Haematoma 12 — Abdominal problems (n=3) Retroperitoneal 1 — haematoma Visceral 1 — dysfunction Abdominal pain 1 — New or progression of old pain (n=5) Low back or 5 — leg pain Vegetative dysfunctions (n=8) Sympathectomy 3 4 effect Disturbance of 1 — miction (? micturition) Vascular problems (n=1) Aortal lesion (at 1 — removal of Outcome measures and their validity: Not stated for subjective measures. Other comments: In particular, patients with an isolated discopathy, who had not had previous back surgery and/or pathology at the same or another level benefited the most from surgery. “From our first and only patient with revision of the prosthesis in this series we learned about its difficulties and dangers.” It was noted the study included a learning curve for technique, criteria and patients selection. 40 Artificial lumbar disc replacement Re-operation rate: Type of re-operation No Re-operation at segment with prosthesis (n=6) Dorsal release 4 + ligamentoplasty (Graf) (1) arthrodesis of facet (1) joints Lateral decompression + (1) block of facet joints + facetectomy (1) Dorsal fusion* 2 At other levels (n=11) Percutaneous nucleotomy 2 Disc prosthesis 7 Discectomy 1 Dorsal release 1 Related to complications (n=3) Release of haematoma 2 Unsuccessful effort to 1a reposition prosthesis Fusion 1a Vascular surgery (aorta) 3a *: after partial removal of facet joint, with prosthesis in situ; a: same patient Table adapted from (Zeegers et al. 1999) Only 25% (3/12) benefited from reoperation. prosthesis) General complications (n=5) Infection of 4 — urinary tract Impotence, 1 — retrograde ejaculation Deep venous 1 — thrombosis Prosthesis (n=2) Malposition 1 1 Table adapted from (Zeegers et al. 1999) Note percentages were not given. Disc migration: No migration (>2mm) noted at 2 years in any of the prostheses. Disc space height: 14% of all levels with a prosthesis showed a decrease in height (> 25%) 2 years after surgery. (disc space height quotient of Farfan) No statistically significant difference in outcomes with regard to the following factors: • Prosthesis positioning • Uni vs Bi vs Tri Replacement • Pure vs post discectomy discopathy • Preoperative duration of low back pain • Good vs a fair technical result 41 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Relative gain: Gain >70 (good) 60-70 (fair) <60 (poor) Complications: Complication No Vascular problems 4.8% (5/105) Temporary 1.9% (2/105) neurological deficits Attributable to 2.9% (3/105) technique Bone 3.8% (4/105)a complications Total 10% (11/105) a: n=1 endplate fracture- revised to fusion n=1 lower endplate subsidence due to osteoporotic bone n=2 periprosthetic ossifications Potential for bias: Most results are reported for the entire group which contains uni, bi and trisegmental replacement patients. It may have been more valid to group the results by the number of segments replaced (ie uni, bi and tri groups). It was not stated if the patients were consecutive or not. Case series LeMaire9 1997, FRANCE 105 patients (154 prostheses implanted) Segment No L3/L4 6 L4/L5 72 L5/S1 76 Prostheses per patient No No prostheses patients 1 58 2 46 3 1 Follow-up: Mean 51 months Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: 50/105 (48%) had undergone 1 or more surgical procedures before the implantation. Time 3 months 1 year Final Work status: Work status % patients 79% 5.8% 15.2% Average relative gain 48.3% 72.8% 82.2% Sedentary workers 81% 17% Light workers 44% 35% Heavy workers 45% 26% 2% 21% 27% Same work Change of work unemployed Total: Work status Same work Change of work unemployed Total 60% 27% 13% Improvement in radicular pain: 96.6 % of patients at 3 months Improvement in back pain: 90.5% of patients at 3 months Prosthesis mobility in degrees: Flexion Extension L4/L5 L5/S1 9.65 6 3.4 3.5 Implant migration (%): Total L4/L5 L5/S1 Anteriorly 33 44 23.5 Centred 56.4 53.7 41.1 Posterior 10.6 2.3 17.6 Note: prosthesis position was measured as the difference between the centre of the prosthesis and the centre of the intervertebral disc (mm). Measurements ≥ 2mm were considered significant. There was a significant correlation between posterior joint pain and anterior positioning of ≥ 4mm. Outcome measures and their validity: Modified Stauffer-Coventry Rating scale used to measure ‘return to work’ and ‘quality of work’ outcomes. Details of this scale were given. Relative gain was calculated as = absolute gain/maximal gain minus preoperative score. Results considered good when relative gain was >70%; fair or satisfactory results were 60-70% gain and <60% was considered poor. Other comments: It was stated “Bad results were attributed to either incorrect indication (osteoporosis, posterior osteoarthritis, overlying thoracolumbar kyphosis), secondary progression of a posterior facet joint syndrome, or nonreturn to work, although the relative gain was equal to or great than 70%”. Lateral bending 4 3.2 42 Artificial lumbar disc replacement Re-operation: 1/105 (1%) because of an endplate fracture, surgery revised to fusion. Ross et al. 1997, UK 46 patients. Follow-up: mean 3 years (range 11-72 months) Oswestry Disability score: Improvement from 52.2 to 33.4 (p=0.001) Revision rate: 2/46 (4.3%) None stated. Potential for Bias: Four patients (9%) either lost to follow-up or had incomplete follow-up data sets. It was not stated if the patients were consecutive or not. Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Outcome measures and their validity: Oswestry Disability Score – validated measure Postal Questionnaire . Selection criteria: Patients deemed suitable for disc replacement using the Oswestry Disability Scoring Instrument Other comments: 43 Artificial lumbar disc replacement Study details Case series Cinotti et al.11 1996, ITALY 46 patients. (36 unisegmental patients and 10 bisegmental patients) Follow-up: minimum 2 years (mean 3.2 years, range 2-5 years) Segment L5/S1 L4/L5 L3/L4 L4/L5 and L5/S1 L3/L4 and L4/L5 No 20 14 2 8 2 Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: Patients were all operated on by the same surgeon. Patients had disc degeneration (n=22) or failed disc excision (n=24). Patients had MRI or CR scans showing a degenerated disc at one or two levels and a painful discography at the same levels. Exclusions: degenerative changes of the facet joints (as seen on CT or MRI scans), disc degeneration adjacent to a fused area and spondylolisthesis. Key efficacy findings Key safety findings Appraisal/Comments Clinical Results: Result No Excellent 24% (11/46) Good 39% (18/46) Fair 30% (14/46) Poor 7% (3/46) (using guidelines previously reported) Complications: Complication No Disc migration 1/46 (2%) Perianular 7/46a (15%) ossification Undersized prosthesis 4/46b (9%) Subsidence on 9/46 (20%) radiograph (without failure of prosthesis) Structural failures 0/46 (0%) (on radiograph) a: 3 patients had a malposition of the prosthesis in the sagittal plane; 4 patients developed spontaneous interbody fusion at the operated levels. b: implant collapsed into vertebral bodies Potential for bias: External assessor used for outcome measures of clinical results and success rate which should decrease bias. A single surgeon performed all procedures, negating any intersurgeon variability. It was not stated if patients were consecutive or not. Re-operation (fusion): Time No Soon after surgery 1/46 (2%) 2-4 years 7/46 (15%) Total 8/46 (17%) (8/17 patients with unsatisfactory results) Success Rate: 69% unisegmental 40% bisegmental (p=0.004) 77% (17/22) no previous back surgery 50% (12/24) previous back surgery (p=0.04) Vertebral motion: L5/S1 Operated level L4/L5 9o (range 0-15 o) 16 o (range 10-21 o) (p=0.003) Disc prosthesis proportion of the length of the endplate in the sagittal plane >80% (range 80-89%) (n=28) 60-76% (n=18) Average vertebral motion at the operated level 12 o It was stated ‘subsidence of the implants into the vertebral bodies and perianular ossifications did not affect the clinical outcome’. Outcome measures and their validity: Well defined definitions of outcomes which had been used in previous publications. Steps taken to optimise the accuracy of ROM measurements also reported. Other comments: Authors concluded that poor patient selection rather than prosthesis limitations was the primary cause of the failure. Authors also noted that the SB Charité III device does not appear to be suitable for implantation at two contiguous levels (unless an undersized prosthesis is placed at the second level or the second device is positioned more anteriorly to provide adequate disc space at both implanted levels). 6o (p=0.01) 44 Artificial lumbar disc replacement Placement Centrally/posteriorly Anterior Postoperative care Exercise 1 week postoperatively Corset for 3 months Vertebral motion (o) 12 5 Range of motion 11o 6 o (p<0.05) No degenerative changes were found at the levels adjacent to the disc replacement in 10 patients who had MRI at follow-up. Postoperative use of analgesics: Frequency No Occasional 9% (4/46) Continuous 26% (12/46) Resumption of work: Level No Same level 67% (31/46) Lower level 20% (9/46) Cannot work 9% (4/46) Unemployed 4.3% (2/46) 45 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Case series Griffith et al. 1994, USA, GERMANY, FRANCE, NETHERLANDS Pain relief: Significant number of patients experienced pain relief both in leg and back pain. (p<0.05) International multi-centre study with retrospective chart review. Leg Pain: 93 patients (139 implants) Segment No L3/L4 15 L4/L5 66 L5/L6 2 L5/S1 55 L6/S1 1 Single prosthesis in 53%, two prostheses in 45% and three prostheses in 2%. Follow-up: mean 11.9 (SD 8.3) months (range 1-37 months). A total of 3.2% (3/93) patients were lost to follow-up. Implant: SB Charité III (DePuy Spine, Johnson&Johnson, Raynham, MA, USA) Selection criteria: Patients from three European surgeons experienced in the implantation of the disc prosthesis participated in the study. Patients had L3-L4, L4-L5, L5-L6, L6-S1 replacements. They had degenerative disc disease, postnucleotomy syndrome, internal disc derangement, failed fusion, instability, or herniated nucleus pulposus. Patients with previous lumbar surgery were included. % reduction Right leg 48% (p<0.05) Left leg 41% (p<0.05) Straight 50% leg raising (p<0.01) test Significant improvement was found in terms of pain intensity compared to preoperative pain scores (p< 0.001). Surgeon A did not report analog pain scale scores. Self-reported walking distance: (%) Improved 39% Decreased 2% Same 58% Data unavailable from Surgeon A. Neurological weakness: 81% reduction in patients with weakness (p<0.01). 43% (3/7) with no preoperative back pain developed postoperative back pain Implant failure: 1% (1/93) minor core failure; a deformation of the metal ring surrounding the polyethylene core. Problems related to prosthetic choice: Implant migration: 5/93(4.3%) Implant dislocation: 1/93 (1% ) Other complications: Not related to device Equivocal (not able to decide if related to device) No 30/93 (32%) (phlebitis/leg thrombosis n=2; injured vein n=16) 16/93 (17%) Potential for bias: Losses to follow-up of three patients (3.2%) Unclear what measures were taken to standardise surgery and outcomes measurement at the various sites (for instance, one surgeon did not use the specified analogue pain scale) No detail given of whether the groups from each centre had similar characteristics. With retrospective chart review, some data may be inadvertently different or missing altogether and follow-up may be inconsistent. Outcome measures and their validity: Ten point analogue pain scale used. Other comments: Many complications noted but obvious care taken to document all complications which could possibly explain the seemingly high rates. The summary and analysis of data was performed by an independent research organization with no corporate affiliation to the manufacturer of the device or surgical investigators. Return to work status: Patients unable to work Preoperatively 40/92 (44%) Postoperatively 37/89 (42%) p=0.83 Results for work status varied between the surgeons. 46 Artificial lumbar disc replacement Re-operation rates: 3/93 (3% ) (revised to percutaneous nucleotomy, foraminoplasty and A-P spinal fusion respectively). Study details Case series David et al.13 1993, FRANCE 22 patients Follow-up: minimum 1 year Implant: SB Charité III Selection criteria: Cases included where fusion in situ is to be avoided (DDD with collapsed disc, failed backs and instability at a maximum of two levels) Key efficacy findings Key safety findings Appraisal/Comments 65% of patients had ‘good to excellent’ results. No loosening of the prosthesis or osteolysis at the bone-prosthesis interface has been noticed in patients with two or more years follow-up. Not stated Potential for bias: The method of patient selection was not detailed, and it was not stated if patients were consecutive or not. Segmental mobility remains on dynamic radiograph. Outcome measures and their validity: No validated measures were used, outcomes appeared to be subjective. Other comments: Author noted that disc replacement surgery is still ‘far from being routine’. 47 Artificial lumbar disc replacement ProDisc II Study details Key efficacy findings Randomised Controlled Trial Delamarter et al. 2003, USA VAS: Part of a multicentre prospective RCT (FDA IDE study). Artificial disc replacement (ProDisc): n=35 Fusion: n=18 1-level surgery ProDisc Fusion L3/L4 n=0 n=1 L4/L5 n=9 n=4 L5/S1 n=10 n=3 2-level surgery ProDisc Fusion L3/L5 n=1 n=0 L4/S1 n=14 n=10 Note: there is a mistake in the table as there should be 16 patients who had 2-level surgery in the ProDisc group. Follow-up: minimum 6 months (6 to 15 months). Clinic visits at 6 weeks, and 3, 6 and 12 months. Implant: ProDisc II (Spine Solutions) Comparison: Artificial disc replacement versus circumferential fusion (standard of care). Selection criteria: Inclusion criteria: age between 18 and 60 years, failed conservative treatment for at least 6 months; minimum Oswestry score of 40/100; and no more than one- or two- level degenerative disc disease from L3 to S1. Exclusions: patients with metal allergies, previous lumbar fusions, compromised vertebral bodies, ProDisc Fusion Preoperative 7.44 6.84 6 weeks 2.89a 4.74† 3 months 3.65 4.78‡ 6 months 4.38 3.96 a a: p<0.05 versus preoperative; †: p<0.01; ‡: p<0.001 Oswestry: Preoperative 6 weeks 3 months 6 months *: p<0.05 ProDisc 31.26 20.65 17.93 15.07 Fusion 30.67 25.00 25.00* 14.57 Range of Motion: ProDisc Mean [SD] range (degrees) Patients treated at L4/L5 Movement at L3/L4 Preoperative 5.48[5.31] -7.00-22.00 6 weeks 5.90[4.59] -1-17.00 3 months 2.55[6.20] -11.00-12.00 6 months 6.89[3.26] 3-13 Movement at L4/L5 Preoperative 7.04[5.60] Fusion Mean[SD] range (degrees) 5.00[2.89] 1.00-9.00 7.50[2.12] 6.00-9.00 Key safety findings Appraisal/Comments Implant failure: There were no incidents of implant migration, breakage, or mechanical failure after disc replacement. Potential for Bias: Randomisation was weighted 1:2 to receive either fusion or the artificial disc. All patients were blinded to the treatment until after the surgery. The average age, gender, narcotic use, smoking history, and worker’s compensation percentage were not statistically significant between the groups. The ADR group had a greater percentage of patients with pain >1 year than the fusion patients (100% vs 89%, p<0.04). The fusion group was smaller which may have influenced statistical significance in that group. Analysis limited to one site with relatively short follow-up time. Outcome measures and their validity: Outcome measurements were all well validated. The consistency of measurement of radiographic angular measurements was assessed by evaluating the untreated L3-L4 intervertebral segments- there were no significant differences before surgery and at 6 months and between groups. Other comments: 11.46[7.86] 48 Artificial lumbar disc replacement and severe facet degeneration. -5.00-18.00 7.62[4.21] -5.00-15.00 3 months 7.55[4.15] -1.00-17.00 6 months 10.11[3.33] 5.00-17.00 Patients treated at L5/S1 Movement at L3/L4 Preoperative 5.75[5.93] -7-22.00 6 weeks 4.88[3.97] -6.00-13.00 3 months 4.06[5.95] -11.00-10.00 6 months 6.23[1.06] 5.00-8.00 Motion at L5/S1 Preoperative 6.17[8.19] -25.50-16.00 6 weeks 5.42[5.80] -10.0-13.00 3 months 8.67[6.46] 1.00-24.00 6 months 7.62[4.43] 2-17.00 0.00-27.00 6 weeks 0.00[4.24] -3.00-3.00 4.75[3.96] -4.0-9.00 7.50[2.38] 6.00-12 3.33[8.23] -10.0-21 4.75[4.19] 2-11 49 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Operative time: Significantly reduced in the ProDisc versus fusion patients. It was not reported whether or not any complications occurred. Appraisal/Comments Randomised Controlled Trial Zigler 2003 USA 39 patients Comparisons: Artificial disc replacement (ProDisc): 28 Fusion: 11 Two-level surgery ProDisc Fusion 5/28 (18%) 1/11 (9%) (3 ProDisc cases were nonrandomized ‘teaching’ cases at the beginning of the study). Follow-up: 6 months, data collected at 6 weeks, 3 and 6 months postoperatively. Implant: ProDisc II Selection criteria: age between 18 and 60 years; at least 6 months failed nonoperative therapy; degenerative disc disease at ½ adjacent vertebral levels between L3 and S1; Oswestry score at least 40%; psychosocially, mentally or physically able to comply with the protocol, including adhering to follow-up and filling out form. Exclusions: >2 degenerative levels; endplate dimensions <34.5mm in coronal plane and/or <27mm in sagittal plane; known allergy to titanium, polyethylene, cobalt, chromium or molybdenum; prior lumbar fusion; posttraumatic vertebral body compromise/deformity; facet joint degeneration; lytic spondylolisthesis or spinal stenosis; degenerative spondylolisthesis of grade >1; back/leg pain of unknown aetiology; osteoporosis; metabolic bone disease; morbid obesity; pregnant or interested in Hospital stay: Shorter in the ProDisc versus fusion patients (2.1 versus 3.5 days). Postoperative rehabilitation: More rapid after ProDisc versus fusion, with ProDisc patients having significant improvements in range of motion compared to preoperative values, and better motion than the fusion patients. Fusion patients had slower recovery to independent ambulation and slower return to recreational activities. Return to work: ProDisc Fusion 8 weeks 16 weeks Oswestry scores: In the ProDisc group, Oswestry scores steadily decreased after surgery, while they increased in the fusion group at 3 months (possibly the result of postoperative immobilisation). Potential for bias: Groups were similar in demographics, including gender, age, weight, smoking history, preoperative medication usage, nonoperative treatment and prior surgeries. Ten patients had single level disc replacement before the two-level arm of the study began. This was a small group size of a larger study, with short follow-up. It comprised the first 39 patients with at least 6 months follow-up. The fusion is expected to appear worse at shorter follow-up times than disc replacement, but this gap may be reduced at longer follow-up. Outcome measurements and their validity: This study was presented in more of a descriptive than quantitative way, with little quantitative objective data with which to compare the groups. Other comments: VAS scores: Decreased in both groups, more so in the ProDisc patients, but this was not statistically significant. Satisfaction scores: Declined sharply in the fusion group at 6 50 Artificial lumbar disc replacement becoming pregnant in next 3 years; active systemic/local infection; medications or drugs known to potentially interfere with bone/soft tissue healing, excluding smoking; rheumatoid arthritis or other autoimmune spondylarthropathies; systemic disease including AIDS, HIV, hepatitis; active malignancy. months, trending towards significance. 51 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Bertagnoli et al. (2005) Germany Clinical Outcomes Device related complications Potential for bias 104 patients were selected for follow-up Preoperative Oswestry disability scores decreased from 53% to 29% at 24 months follow-up. There were no cases of loosening, subsidence, migration, metallic or polyethylene failure, allergic reaction/rejection, visceral or neurologic injuries caused by the implant components, and/or infection. Only patients who completed the 24 month follow-up period were included in this study (104 of a possible 118 patients fulfilled the follow-up criteria). Case series Single level DDD Follow-up: Pateints were assessed at 3, 6, 12 and 24 months post-surgery Implant: ProDisc II Inclusion criteria Prospective data was compiled for single-level Prodisc procedures from March 2000 to December 2001. Patients aged 18 to 60 years were enrolled. All patients had disabling discogenic low back pain with or without radicular symptoms resulting from DDD from L3 to S1 as comfirmed bymagnetic resonance imaging, computed tomography and, when indicated, discography. Exclusion criteria Patients with spinal stenosis, osteoporosis, prior fusion surgery, chronic infections, metal allergies, pregnancy, facet arthrosis, inadequate vertebral end-plate size, more than one level of spondylosis, neuromuscular disease, , pregnancy, Worker’ Compensation, spinal litigation, BMI >35, and/or any isthimic or degenerative spondylolisthesis greater than Grade I. The decrease in Oswestry disability scores occurred primarily in the first 3 months post-surgery (Repeated measures GLM analysis: F(1,103) = 132.80, p<0.001, ŋ2 = 0.56) and was sustained for 24 months (F(1,103) = 113.71, ŋ2 = 0.53). No significant changes were observed from 3 months to 24 months follow-up. VAS decreased from 7.6 to 3 at 24 months. Significant change was noted in the first 3 month post-surgery (F(1,103) = 222.64, p<0.001, ŋ2 = 0.68). This was sustained until the 24 month follow-up (F(1,103) = 161.361, ŋ2 = 0.61, p<0.001. Patient Satisfaction (%) 3 59.2 Months 6 12 57.8 55.4 24 58.3 Satisfied 34.0 27.4 32.8 38.5 Unsatisfied 4.8 14.7 11.9 3.1 Completely satisfied Approach related complications Outcome measurements and their validity: Outcome measurements were generally well validated. Other comments: Two cases of retro peritoneal hematomas and a single subcutaneous hematoma was diagnosed during the perioperative period. One case of retrograde ejaculation which recovered spontaneously at 6.5 months post-surgery. One case of persistent leg pain after complication of an L5-S1 implant which required posterior exploration and decompression. Posterior subarticular stenosis was identified and the patient continues to be unsatisfied with her outcome at 32 months post index procedure. 52 Artificial lumbar disc replacement Back Pain (%) No pain Occasional pain Regular pain Preop 0 15.3 3 21.3 67.0 84.6 11.6 Months 6 12 22.8 28.7 62.4 59.4 14.8 24 32.0 59.2 11.9 9.0 Months 6 12 60.4 45.2 28.6 41.6 24 62.6 29.5 Radicular Pain (%) No pain Occasional pain Regular pain Preop 11.9 45.5 3 53.6 36.1 42.6 10.3 11.0 13.2 8.8 Medication usage Medication (nonsteroidal anti-inflammatories, narcotics and morphine derivatives) usage decreased significantly compared to pre-operative usage rates. Radiographic Analysis Median preoperative height of affected discs was 4mm presurgery, after surgery disc heights were increased to a median of 13mm (p<0.001). Motion of affected discs increased from 3º before surgery to 7º after surgery (p<0.004). Height of adjacent level discs did not change significantly post-surgery. 53 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Early postoperative complications: none Potential for bias: The study included only two patients with complications and did not mention the total number of patients who had the operation, meaning the rate of artificial disc dislocation is unknown. Case series Aunoble et al. 2004, FRANCE n=2 L5-S1: n=2 Follow-up: ~4 -20 months Implant: ProDisc II Selection criteria: Not stated Oswestry score: Improvement of 60% up to 4 months postoperatively in 1 patient; and from 44 to 10% in the other patient. Re-operation: A fusion was performed in both patients. Dislocation of disc: n=2 In patient 1, after 4 months the patient began to experience severe acute low back pain, x-ray showed an anterior dislocation of the polyethylene. In patient 2, 1 month postoperatively severe pain was experienced with radiographs showing L5-S1 listhesis (grade 1) and evidence of polyethylene inlay dislocation. The patient became free of pain again until 19 months after surgery when the back pain worsened (Oswestry score 24%) and because of a risk of metallosis in relation with micromotion, a fusion was performed. Outcome measurements and their validity: The Oswestry score is well validated. Other comments: 54 Artificial lumbar disc replacement Study details Case series Tropiano et al. 2003, FRANCE n=53 December 1999 to December 2001 evaluation of patients who had previous lumbar disc replacements. 11/53 (21%) had one prior surgery; 9/53 (17%) had two or more prior surgeries; 33/53 (62%) had no prior surgery. Segment No L5/S1 27 L4/L5 13 L4/L5 and L5/S1 9 L3/L4 and L4/L5 2 L3/l4, L4/L5 and 2 L5/S1 Follow-up: Mean 1.4 years (1 to 2 years) Implant: ProDisc II Selection criteria: Disc degeneration (n=33), failed spine surgery (n=20). All patients had at least 6 months of severe back pain and had failed non-surgical treatment. Exclusions: Known chronic disease of major organ system; history of local infection; pregnancy; associated facet degeneration; history of abdominal or retroperitoneal surgery near planned anterior approach; osteoporosis or osteopenia; structural spinal deformities; absence (postoperative) of posterior elements (eg. after laminectomy and facetectomy). Key efficacy findings Key safety findings Appraisal/Comments Surgery times and hospital stay: Time Operative time Mean 104 min (range 32-250 min) Hospital stay Mean 9 days (range 4-31 days) Total Complications: 5/53 (9%) Potential for bias: The clinical evaluation and questionnaire administration were performed by individuals not directly involved in patient selection, surgery, or postoperative care, reducing the potential for bias. It was not stated if the patients were consecutive or not. One surgeon performed all procedures, minimising inter-surgeon variability. Patient satisfaction: Satisfaction No Entirely satisfied 46/53 (87%) Satisfied 7/53 (13%) Not satisfied 0/53 (0%) 32/33 (97%) of patients with no previous surgery reported satisfactory results and 10/11 (90%) of those with previous lumbar surgery reported satisfactory results. Resumption of work and activities of daily living: Function No Full 38/53 (72%) Slightly limited 15/53 (28%) VAS lumbar: Preoperative 3 months 6 months Mean 1.4 years *: p<0.05 VAS Mean[SD] 7.4[2.5] 1.8[ 2.1]* 1.4[ 2.2]* 1.3[ 1.8]* Vertebral body fracture: 1/53 (2%) Implant malposition: 2/53 (4%) Persistent radicular pain: 2/53 (4%) (no radiographic evidence of neural compression; resolved after 3 and 5 months) Mechanical failure/loosening: No radiolucent or sclerotic lines were noted in reponse to the implant; there were no periannular ossifications and no mechanical implant failures. No degenerative changes were seen at the levels adjacent to the disc replacement or at the facet joints. Outcome measurements and their validity: Valid outcome measures were used. Other comments: Clinical results of patients with single or multilevel surgery were equivalent and results were good in patients with previous lumbar surgery. The vertebral fracture occurred in a woman with unrecognised osteopenia. There was an increase in lordosis, related to the lordotic shape of the implant. Complications were not related to the device, but to errors in judgement and technique by the surgeon, or from the anterior approach. Authors believe the primary indication for ProDisc II implantation is in patients with single- or multilevel lumbar discopathy with 55 Artificial lumbar disc replacement VAS radicular: Preoperative 3 months 6 months Mean 1.4 years *: p<0.05 VAS Mean[SD] 6.7[ 3.0] 2.8[3.2]* 1.6[ 2.8]* 1.9[ 2.6]* Oswestry: Preoperative 3 months 6 months Mean 1.4 years *: p<0.05 Mean[SD] 56[ 8.2] 30[ 10.1]* 18[ 9.9]* 14[7.4]* disc collapse and intersegmental hypermobile instability without significant posterior changes, between 18 and 60 years of age. Secondary indications include patients with lateral recess stenosis due to disc degeneration and loss of disc space height, patients with single- or multilevel postdiscectomy syndrome or failed back surgery syndrome, and patients with discopathy adjacent to a fusion. These secondary indications need a larger patient cohort for confirmation. Comparison of patients with 1-level or multilevel disc replacement: 1-level Multilevel (n=40) (n=13) Mean[SD] Mean[SD] VAS lumbar 7.4[ 2.3] 7.4[ 3.4] preoperative VAS lumbar last 1.3[ 1.7] 1.3[ 2.1] follow-up VAS radicular 6.5[ 3.1] 7.4[ 2.5] preoperative VAS radicular last 2.2[ 2.8] 1.2[ 1.9] follow-up Oswestry 27[ 8.4] 31[ 7.1] preoperative Oswestry last follow- 8[ 8.1] 5[ 4.7] up 56 Artificial lumbar disc replacement Radiographic findings: Flexion-extension after surgery L5-S1 L4-L5 (degrees) (degrees) 10 Range of 8 range 2-12 range 8-18 motion Mean lumbar lordosis: Before surgery Final follow-up 56.7 o range 30-72 o 61.9 o range 46-72 o Reoperation: 3/53 (6%) (1 case of vertebral body fracture and 2 cases of malposition) 57 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Case series Bertagnoli & Kumar 2002, GERMANY Clinical outcome: Postoperative complications: 1/108 (systemic septicaemia, resolved with antibiotics) Potential for bias: Operations were performed by a single surgeon, reducing variability caused by different surgeons. It was not stated if the patients were consecutive or not. n=108 (134 prosthetic discs) Operations performed by a single surgeon. Disc degeneration (vertical instability; n=67); failed disc surgery syndrome (35); transition zone syndrome (n=6). Segment No L5/S1 61 L5/L6 3 L4/L5 31 L3/L4 7 L2/L3 3 L4/L5 and L5/S1 10 L2/L3 and L4/L5 1 L3/L4 and L4/L5 and 2 L5/S1 Note: not sure of denominator, numbers add to 118. Follow-up: 3 months to 2 years; 54 patients for more than 1 year. Implant: ProDisc II Selection criteria: All patients had previously been treated with conservative management for a minimum of 6 months, and all had a positive preoperative response to discography. Exclusions: Severe osteoporosis, physiological dysfunction, history of previous disc infection, severe posterior element pathologies, fracture of the vertebra, and tumours. No Excellent 98/108 (91%) Good 8/108 (7%) Fair 2a/108 (2%) Poor 0/108 (0%) a : both patients had advanced disc degeneration also involving the adjacent levels and secondary osteoarthrosis of the facet joints. Residual leg or back pain: 9/108 (8%) Analgesic use: > 2 weeks 6 months to 1 year Occasionally No 45 12 33 Resumption of duties of daily living: Mean 2.3 weeks (range 1.5 to 3.2 weeks) Ability to resume work (n=54, follow-up of >1 year): No At same level 35/54a (65%) At lower level 17/54 (31%) Not able to resume work 2/54 (4%) a: patients with more than 1 year follow-up Average range of vertebral motion: Segment Mean (range) degrees L5-S1 9 (2-13) L4-L5 10 (9-13) L3-L4 10 ( 8-15) L2-L3 12 ( 9-15) Implant loosening or subsidence of prosthesis: None Structural disc failure: None Outcome measurements and their validity: Validated measures, such as VAS and Oswestry scores, were not performed. It was not stated what constituted an excellent, good, fair or poor clinical outcome. Other comments: All operations were performed using less invasive techniques. The following categories of indications for surgery were stated: Prime: single disc level; >4 mm remaining disc height; no osteoarthritic changes to facet joints; no adjacent level degeneration; intact posterior elements. Good: single or double level; >4mm remaining disc height; no primary osteoarthritic changes to facet joints; minimum degeneration of adjacent discs; minimum posterior segment instability. Borderline: single, double or triple level; <4mm remaining disc height; primary osteoarthritic changes to facet joints; minimum adjacent level degeneration; minimum posterior segment instability; adjacent to 58 Artificial lumbar disc replacement Average range of vertebral motion at adjacent segments compared to preoperative range: No Decreased range 5o 6/108 (6%) Range 3-8o Increased range 6o 86/108 (80%) Range 3-8o Unchanged 16a/108 (15%) a : 12 patients had presented with advanced degenerative disc disease prior to surgery; 4 patients had secondary changes of the facet joint in addition to advance degenerative disc disease prior to surgery. fusions. Poor: single, double or triple level; gross degeneration of the spine; secondary osteoarthritic changes to the facet joints; <4mm disc height at the adjacent levels; posterior segment instability. Progression of disc degeneration at adjacent levels: 5/108 (5%; at L5-S1 in 3 and at L4-L5 in 2; all patients presented with an anterior disc height of <7mm) Outcome relative to indication for surgery: % patients (range) Prime 98 (96-99%) Good 93 (89-97%) Borderline 83 (79-88%) 59 Artificial lumbar disc replacement Study details Case series Mayer et al. 2002, GERMANY n=34 first consecutive patients multicentre study June 2000 to March 2002 Segment L5/S1 L5/L6 L4/L5 L4/L5 and L5/S1 L2/L3 No 24 3 3 3 1 Follow-up: Mean 5.8 ± 3.0 (SD) months (26/34 patients reached follow-up, the others were <3 months postoperative. Key efficacy findings Key safety findings Appraisal/Comments Operating time: Mean 130.9[45.9] minutes (range 88-300 minutes) Blood loss: 117 ml per level (range 30-350 ml) Potential for bias: Patients were consecutive, reducing the risk of selection bias. Hospital stay: Mean 12.0 days (range 4-25 days) Patient satisfaction at last follow-up: (%) Completely satisfied 60.9 Satisfied 21.7 Not satisfieda 17.4 a: all the patients who were not satisfied said they would undergo the operation again if they were faced with the same choice. VAS score: Implant: ProDisc II Selection criteria: Causes of disc degeneration were: degenerative disc disease (21/34); degenerative disc disease + disc herniation (4/34); FBS or postoperative osteochondrosis (5/34); adjacent level degeneration (3/34); degenerative following nucleus replacement (1/34). Preoperative Reduction after surgery Mean VAS score 6.3 3.9, range 8.4 point reduction to 7.5 point increase Oswestry score: Preoperative Reduction after surgery Mean[SD] 19.1[7.4] range 1-32 11.5[9.6] range 27 point reduction to 12 point increase Lower back pain: None in 76% of patients at their last follow-up. Loosening or migration of implant: None Subsidence of adjacent vertebrae: None Complications related to surgical procedure: 3/34 Nerve root irritation: 1/34 (irritation of the L5 nerve root several days postoperatively; CAT scan showed an extra-foraminal protrusion of nucleus material compromising the L5 nerve root on the left side. Neurological exam was normal and a 3 week outpatient course of conservative treatment was successful) Inlay dislocation: 1/34 (patient had an increase of pain 5 weeks after surgery with no notable trauma; radiographs showed an inlay dislocation anteriorly; it was believed the polyethylene inlay was not completely snapped into the inferior endplate; a new implant was successfully used). Retrograde ejaculation: 1/34 Outcome measurements and their validity: Validated outcome measures were used. Other comments: Surgery was performed using minimally invasive techniques using a mini-laparotomy. The ‘medium’ ProDisc was used in 36/37 segments and ‘large’ was used at one level. The implant with 6o lordosis angle was used in 65.4% of cases, the 11o angle was used in 34.6% of cases. The polyethylene inlay of 10 mm height was used in 34 segments; the 12mm inlay in two segments; and the 14m inlay in one segment. Postoperative fusion: None 60 Artificial lumbar disc replacement Acroflex Acromed Study details Key efficacy findings Key safety findings Appraisal/Comments 67% (4/6) of patients had a satisfactory result: Result No Excellent 1 Good 2 Fair 1 Poor 2 Satisfactory level of bony ingrowth in all prostheses. Potential for bias: Small sample size, it was not stated if the patients were consecutive or not. Case series Enker et al.14 1993, USA 6 patients Follow-up: 3.4 years (range 3-4 years) Implant: DePuy Acroflex Acromed (AcroMed Corporation, Cleveland, OH, USA) Selection criteria: Patients requiring single level replacement only (disc degeneration in the lumbosacral spine in five patients and isolated disc resorption in one patient) Four patients had had previous spinal surgery. All patients had confirmatory discography. Exclusions: Previous decompressive laminectomy, osteopenia, facet joint arthritis, spinal stenosis, disc hernation, pseudoarthrosis, arachnoiditis, psychological dysfunction, abdominal wall hernail, previous iliofemoral phlebitis, prior retroperitoneal radiation and history of discitis or vertebral osteomyelitis. Lateral flexion/extension: Average 8o (range 2-16 o) Anterior translation: Average of 2.3 mm (range 0-4 mm) Reoperation rate: 1/6 (17%) due to implant failure- a fracture through the rubber core of the implant evident on radiograph. Radiographic changes: Annular ossification occurred in two patients, one of whom had autofusion, the second still had angular motion on lateral flexion/extension radiographs. There were no cases of vertebral endplate erosions, sclerosis, or vertebral body remodeling, component end plate debeading, adjacent-level disc degeneration or local or systemic complications. Outcome measures and their validity: What constitutes an excellent, good or fair clinical outcome was carefully detailed (but not a validated scale). Other comments: After publication of this article, the Acromed device was re-designed so that only a single piece of rubber was used as the inner core component. 61 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Appraisal/Comments Operating time: Mean 135 minutes Blood loss: Mean 140 ml Potential for bias: It was not stated if the patients were consecutive or a selected group. Hospital stay: Mean 6.3 days Operative complications: None Outcome measures and their validity: Valid outcome measures were used. Clinical results at 1 year: Displacement of implant: Early partial displacement in one case. Other comments: The purpose of the study was to “evaluate the design of a titanium/polyolefin artificial disc, refine the surgical technique, assess safety and measure outcome to determine if an RCT is justified.” Cine-fluoroscopy was superior in demonstrating vertebral motion compared to standing lateral flexion/extension radiographs. “Although a satisfactory clinical outcome was obtained, technical difficulties with insertion, the case of partial implant displacement and radiological evidence of suboptimal endplate contact have led to refinement of the titanium endplates.” Case series Freeman et al.14 2001, AUSTRALIA (abstract) 11 patients Follow-up: 2 years (n=3) and 12 months (n=8) Clinical assessment carried out preoperatively and at 6 and 12 weeks, 6 months and 1 and 2 years. Surgery since April 1998 L5/S1 n=10 Implant: AcroFlex Selection criteria: All patients entering the pilot study had single level disc disruption at L4/L5 or L5/S1 with disabling lower back pain of at least 12 months duration. Diagnoses were confirmed by discography and an independent assessment included physical examination, visual analogue scales (VAS) for pain, Low Back Outcome Score (LBOS), Oswestry Disability index (ODI), SF-36, lateral flexion-extension radiographs and MRI. VAS ODI LBOS SF-36 Average improvement 39% 12 pt 14 pt Improvement in 5/8 sub/scales Vertebral motion: In 10 patients satisfactory movement of the vertebral motion segment was shown by cine-fluoroscopy. Heterotopic calcification: One late case. 62 Artificial lumbar disc replacement Study details Key efficacy findings Key safety findings Oswestry score: Time Score 6 months 82% 1 year 86%a a this exceeded the acceptance criteria of the study of 75% Disc subsidence at 1 year: None (based on detection threshold of 2mm) Appraisal/Comments Case series Le Huec et al.2003, FRANCE (abstract) n=30 L4/L5 or L5/S1 Follow-up: 1 year Implant: Maverick lumbar Disc Prosthesis (Medtronic, USA) Selection criteria: Patients requiring a single level implant with symptomatic low back pain resistant to conservative treatment for more than 1 year. VAS: Time Preoperative Postoperative Mean[SD] 7.1[2] 2.7[1.8] Range of motion: Mean 6 ± 4o (range 3-12o) Device migration: No evidence of anterior and/or posterior migration. Spondylotic bridging of implant disc space: No evidence. Removal or revision of prosthesis: None Potential for bias: The range of motion was determined by an independent radiologist. The follow-up was too short to assess longer term outcomes. It was not stated whether or not the patients were consecutive. Outcome measures and their validity: Valid outcome measures were used. Other comments: The study was in abstract form only, limiting the available outcome data. Non-device complications: 1/30 (3%, injury to ureter) 63