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  ["project_title"]=>
  string(96) "LimiFlex Clinical Trial for the Treatment of Degenerative Spondylolisthesis With Spinal Stenosis"
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  string(683) "The LimiFlex? Clinical Trial is a prospective, concurrently controlled, multi-center study to evaluate the safety and effectiveness of decompression and stabilization with the Empirical Spine LimiFlex? Paraspinous Tension Band compared to decompression and transforaminal lumbar interbody fusion (TLIF) with concomitant posterolateral fusion (PLF) for the treatment of lumbar degenerative spondylolisthesis (Grade I per Meyerding classification) with spinal stenosis. The objective of this data request is to supplement the control group with historically obtained data from qualifying subjects.    Note that the original sponsor of the requested study is supportive of this request."
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      string(2) "MD"
      ["p_pers_pr_affil"]=>
      string(15) "Empirical Spine"
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      string(2) "no"
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      string(6) "Marcia"
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      string(6) "Wachna"
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      string(2) "RN"
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      string(15) "Empirical Spine"
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  string(15) "Empirical Spine"
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      string(161) "NCT00316121 - A Prospective, Multicenter, Randomized Study Comparing the Use of HEALOS® to Autograft in a Transforaminal Lumbar Interbody Fusion (TLIF) Approach"
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  ["property_scientific_abstract"]=>
  string(1576) "Background:  Degenerative spondylolisthesis (DS) with lumbar spinal stenosis (LSS) is commonly treated with decompression and fusion. Fusion has been shown to be effective, however is associated with significant morbidity and cost. The LimiFlex paraspinous tension band (PTB; Empirical Spine, San Carlos, CA) is an alternative stabilization technique for patients receiving surgical decompression for DS with LSS.
Objective: The objective of this multi-center study is to evaluate the safety and effectiveness of decompression and stabilization with the PTB compared to decompression and transforaminal lumbar interbody fusion (TLIF) with concomitant posterolateral fusion (PLF) for the treatment of DS with LSS.
Study Design: This is a multi-center, prospective, concurrently controlled, non-blinded study. Balance between groups will be achieved through sub classification using propensity scores.
Participants: The prospectively enrolled control group will be supplemented with retrospectively enrolled control subjects recruited from participating study sites, as well as subjects meeting inclusion criteria from the requested HEALOS study data.
Outcome Measures: Non-inferiority of the investigational group will be assessed with composite clinical success criteria including 15 point reduction of oswestry disability index, no new or worsening persistent neurologic deficit, and no device integrity failures.
Statistical Analysis: Non-inferiority will be assessed in a stratified analysis among propensity score-ranked quintiles." ["project_brief_bg"]=> string(3180) "Degenerative spondylolisthesis is a common clinical condition of the lumbar spine in which there is anterior translation of the superior vertebra relative to the inferior vertebra, with an intact neural arch and degenerative changes of the facet joints. It rarely occurs before the age of 50 years, and it disproportionately affects women, with a female:male ratio of 6:1. Degenerative spondylolisthesis is typically associated with degenerative changes which render the facet joints less resistant to shear forces borne by the segment.
Patients with degenerative spondylolisthesis typically present with symptoms of stenosis, which are relieved surgically with a decompression/laminectomy. Unfortunately, however, the removal of tissue involved in the decompression increases the flexion instability of the spinal segment, and, over time, the listhesis can increase and cause symptoms to recur. Although some studies report good results in patients who receive only a decompression, including two studies which suggest that more limited decompressions preserve sufficient stability without the need for fusion, most suggest that fusion of the segment after decompression provides clinical benefit. Recently, the results of a randomized clinical trial comparing decompressions alone to decompressions and fusion demonstrated that the increasing postoperative segmental flexion in patients with decompression was associated with increasing anterior translation and a poor clinical result. As a result of these findings, the predominant surgical approach in the United States is to treat degenerative spondylolisthesis patients with a decompression and fusion to ensure a good clinical outcome.
Decompression with instrumented fusion, while the standard of care, is still an invasive surgical option and not appropriate or desirable for many patients due to its complication rate and postoperative morbidity. Complications associated with implantation of fusion instrumentation are well understood: these include vascular injury, direct nerve root injury, or disruption of facet joints outside of the segment to be fused. The amount of dissection and retraction of the paraspinal musculature required during the fusion procedure is significantly increased relative to a decompression-alone to allow for the placement of pedicle screws and bone graft. Average blood loss and operative time for instrumented fusion have been reported to be over 600 ml and over 4 hours, respectively. In comparison, current decompression techniques have reported blood loss in the range of 30-50 ml and operative times of less than 2 hours. The additional operative time and exposure results in increased general peri-operative complications associated with their use, including cardiopulmonary complications and infection.
The PTB is designed to allow the surgeon to perform a decompression to treat the presenting symptoms and then apply the device to stabilize the segment. As such, it presents a new stabilization option for patients for whom a surgeon would like to add stability to a decompression without adding the potential risks, morbidity and complications of a fusion." ["project_specific_aims"]=> string(650) "The primary study objective is to demonstrate the safety and effectiveness of the PTB when used for spinal stabilization, at one level from L1 to S1, in skeletally mature patients following surgical decompression for treatment of lumbar degenerative spondylolisthesis (Grade I per Meyerding classification) with spinal stenosis.
The objective of the present data request is to supplement the control group with historically obtained data from qualifying subjects. Note that the original sponsor of the requested study has been contacted, is supportive of this request, and advised that the data should be requested through the YODA project." ["project_study_design"]=> string(0) "" ["project_study_design_exp"]=> string(0) "" ["project_purposes"]=> array(0) { } ["project_purposes_exp"]=> string(0) "" ["project_software_used"]=> array(2) { ["value"]=> string(86) "not_analyzing_participant_level_data__plan_to_use_another_secure_data_sharing_platform" ["label"]=> string(92) "I am not analyzing participant-level data / plan to use another secure data sharing platform" } ["project_software_used_exp"]=> string(235) "Patient-level data will be screened for inclusion/exclusion criteria within the YODA portal. Once subjects meeting eligibility criteria have been identified, a data sharing agreement will be put in place directly with the Data Holder." ["project_research_methods"]=> string(723) "Detailed Inclusion/Exclusion criteria are published for NCT03115983 on clinicaltrials.gov. Data sources will include prospective investigational and control subjects enrolled at participating study sites; retrospective control subjects included by participating study sites; and historical control patients from the requested YODA data set meeting inclusion/exclusion criteria.
Individual subject level data from the requested study will be screened for inclusion in the broader study. Only data from included subjects will be utilized. Note that the original sponsor of the requested study has been contacted, is supportive of this request, and advised that the data should be requested through the YODA project." ["project_main_outcome_measure"]=> string(632) "The main outcome measures utilized in the primary endpoint include Oswestry Disability Index, neurologic exam results, reoperations/revisions, and radiographic device condition. Secondary outcome measures include the individual components of the primary endpoint, as well as Estimated blood loss, Length of procedure, Hospital stay, Return to normal activities of daily living, Work status, Pain medication including narcotics usage, Visual analog scale (VAS) leg pain, Visual analog scale (VAS) back pain, Zurich claudication questionnaire (ZCQ), SF-12 Quality of Life survey, Patient satisfaction and Radiographic fusion status." ["project_main_predictor_indep"]=> string(584) "The main predictor independent variable is a Composite Clinical Success (CCS) endpoint evaluated at 24 months follow-up that will assess individual success for patients in the investigational LimiFlex or control fusion arm . To be considered a success, a subject must demonstrate ALL of the following components of the CCS at 24 months:
- 15 point improvement in Oswestry Disability Index (100 point scale)
- Absence of a new or worsening, persistent neurological deficit
- Absence of additional surgical intervention
- Absence of device integrity failures" ["project_other_variables_interest"]=> string(885) "Secondary outcomes include:
? Each of the individual components of the composite primary endpoint
? Estimated blood loss and units of blood transfused
? Length of procedure (skin to skin)
? Hospital stay
? Length of time for subject to return to his/her normal activities of daily living
? Work status and days to return to work (as appropriate)
? Medication use for pain, including narcotic usage
? Leg pain as measured on a Visual Analog Scale (VAS)
? Back pain as measured on a Visual Analog Scale (VAS)
? Zurich Claudication Questionnaire (ZCQ)
? Quality of Life through use of the SF-12 Health Survey
? Patient satisfaction
? Radiographic fusion status
Economic parameters will be collected to assess and compare the cost-effectiveness of the investigational and control procedures." ["project_stat_analysis_plan"]=> string(4012) "The treatment arm (LimiFlex Paraspinous Tension Band) is compared to a transforaminal lumbar interbody fusion with concomitant posterolateral fusion with pedicle screw instrumentation (control arm) following decompression. The primary effectiveness analysis is a responder analysis at 24-months post-operative where a subject is a responder if each of the following are satisfied:
? Function - Improvement of at least 15 points (of 100) on the Oswestry Disability Index (ODI) from baseline compared to 24 months
? Neurological status - Absence of a decrease in neurologic status (motor or sensory) at 24 months compared to baseline unless attributable to a concurrent medical condition or other cause unrelated to the device and/ or study procedure
? Surgical Intervention - Absence of additional surgical intervention, in a separate surgery subsequent to the index procedure, defined as revision, removal, reoperation or supplemental fixation/fusion at the instrumented level or levels adjacent to the instrumented level, over the initial 24 months
? Device Integrity - Absence of integrity failures, defined as device breakage, device separation or disassembly, or device dislocation over the initial 24 months
The primary non-inferiority test will be conducted based on statistically combining within propensity score (PS) subclass comparisons of Month 24 composite clinical success rates between device groups. To conduct the non-inferiority test, the lower bound of a PS subclass adjusted one-sided 95% confidence interval for the difference in success rates will be determined. If this lower bound is larger than -0.125 it will be concluded that the investigational device is clinically non-inferior to control in terms of Month 24 composite clinical success. If the non-inferiority is demonstrated in this way, the same lower bound will be compared to zero and if it exceeds zero, superiority will be claimed. By the closed testing principle, there is no multiplicity adjustment needed for this test of superiority.
Kaplan-Meier survival analysis will be used to characterize and compare failure time distributions between groups stratifying on propensity score quintile where failures include device failure, revisions, reoperations, removals or supplemental fixations for each treatment group. Logistic regression analysis will be used to assess potential factors associated with success or failure of the investigational device including age, gender, BMI, and baseline ODI. Descriptive analyses of continuous secondary endpoints and other relevant variables will include computation of device group specific descriptive statistics including means, standard deviations, medians, minimum, and maximum values. Categorical variables will be summarized using counts and percentages. Specific adverse events and classes of adverse events (e.g., device-related, serious, severity) will be summarized according to the total number of events occurring as well as according to subject specific incidence rates. Counts of the numbers of specific events occurring during discrete time intervals over time and according to severity will be tabulated by device group. Device group differences in classes of adverse events will be summarized using PS subclass adjusted normal distribution based 95% confidence intervals when there are sufficient data to permit this type of analysis. Specific adverse event rates will be summarized using exact 95% confidence intervals for the difference in two binomials but will not account for PS subclass.
As described above, there may be as many as three sources of controls, prospective concurrent controls, retrospective controls, and historical controls or LimiFlex subjects. Primary and secondary effectiveness endpoints will be compared among investigational device subjects, prospective concurrent controls, retrospective controls, and historical controls or LimiFlex subjects, depending upon the number of sources utilized." ["project_timeline"]=> string(277) "Enrollment complete: End of 2019
Primary endpoint completion: End of 2021
Primary analysis complete and FDA submission: 2022
Primary manuscript and results posted to YODA: 2023
Final report (with 5-year follow-up, beyond primary endpoint): 2025" ["project_dissemination_plan"]=> string(569) "Several manuscripts are expected from this study: primary and secondary clinical outcomes; economic cost-effectiveness studies; radiographic outcomes; and long-term (beyond primary endpoint) clinical, radiographic and economic outcomes. Target journals, ranked by priority, are as follows:
- The Spine Journal [Spine J]
- Spine [Spine (Phila Pa 1976)]
- The Journal of Neurosurgery: Spine [J Neurosurg Spine]
- Journal of Bone and Joint Surgery [J Bone Joint Surg Am]
- International Journal of Spine Surgery [Int J Spine Surg]" ["project_bibliography"]=> string(8645) "

1. Weinstein JN, Lurie JD, Tosteson TD, et al. Surgical versus nonsurgical treatment for lumbar degenerative spondylolisthesis. N Engl J Med. 2007;356(22):2257-2270.
2. Herkowitz HN. Spine update. Degenerative lumbar spondylolisthesis. Spine (Phila Pa 1976). 1995;20(9):1084-1090.
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8. Johnsson KE, Willner S, Johnsson K. Postoperative instability after decompression for lumbar spinal stenosis. Spine (Phila Pa 1976). 1986;11(2):107-110.
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10. Matsudaira K, Yamazaki T, Seichi A, et al. Spinal stenosis in grade I degenerative lumbar spondylolisthesis: a comparative study of outcomes following laminoplasty and laminectomy with instrumented spinal fusion. J Orthop Sci. 2005;10(3):270-276.
11. Martin CR, Gruszczynski AT, Braunsfurth HA, Fallatah SM, O’Neil J, Wai EK. The surgical management of degenerative lumbar spondylolisthesis: a systematic review. Spine (Phila Pa 1976). 2007;32(16):1791-1798.
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13. Fischgrund JS. The argument for instrumented decompressive posterolateral fusion for patients with degenerative spondylolisthesis and spinal stenosis. Spine (Phila Pa 1976). 2004;29(2):173-174.
14. Kornblum MB, Fischgrund JS, Herkowitz HN, Abraham DA, Berkower DL, Ditkoff JS. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective long-term study comparing fusion and pseudarthrosis. Spine (Phila Pa 1976). 2004;29(7):726-733; discussion 733-724.
15. Ghogawala Z, Benzel EC, Amin-Hanjani S, et al. Prospective outcomes evaluation after decompression with or without instrumented fusion for lumbar stenosis and degenerative Grade I spondylolisthesis. J Neurosurg Spine. 2004;1(3):267-272.
16. Chou R, Baisden J, Carragee EJ, Resnick DK, Shaffer WO, Loeser JD. Surgery for low back pain: a review of the evidence for an American Pain Society Clinical Practice Guideline. Spine (Phila Pa 1976). 2009;34(10):1094-1109.
17. Glassman SD, Carreon LY, Djurasovic M, et al. RhBMP-2 versus iliac crest bone graft for lumbar spine fusion: a randomized, controlled trial in patients over sixty years of age. Spine (Phila Pa 1976). 2008;33(26):2843-2849.
18. Hatta Y, Shiraishi T, Sakamoto A, et al. Muscle-preserving interlaminar decompression for the lumbar spine: a minimally invasive new procedure for lumbar spinal canal stenosis. Spine (Phila Pa 1976). 2009;34(8):E276-280.
19. Yoshida M, Ueyoshi A, Maio K, Kawai M, Nakagawa Y. Surgical Procedures and Clinical Results of Endoscopic Decompression for Lumbar Canal Stenosis. In: Dezawa A, Chen P-Q, Chung J-Y, eds. State of the Art for Minimally Invasive Spine Surgery: Springer Tokyo; 2005:15-24.
20. Irwin ZN, Hilibrand A, Gustavel M, et al. Variation in surgical decision making for degenerative spinal disorders. Part I: lumbar spine. Spine (Phila Pa 1976). 2005;30(19):2208-2213.
21. Resnick DK, Choudhri TF, Dailey AT, et al. Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 9: fusion in patients with stenosis and spondylolisthesis. J Neurosurg Spine. 2005;2(6):679-685.
22. Resnick DK, Watters WC, 3rd, Sharan A, et al. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 9: lumbar fusion for stenosis with spondylolisthesis. J Neurosurg Spine. 2014;21(1):54-61.
23. Berlemann U, Jeszenszky DJ, Buhler DW, Harms J. Facet joint remodeling in degenerative spondylolisthesis: an investigation of joint orientation and tropism. Eur Spine J. 1998;7(5):376-380.
24. Rundell S, Isaza J, Guillory S, Day J, Kurta S. The Role of Facet Contact in Reducing Intervertebral Shear during Simulated Standing. Paper presented at: 10th Meeting of the Spine Arthroplasty Society; April 27-30, 2010; New Orleans, LA.
25. Sato K, Wakamatsu E, Yoshizumi A, Watanabe N, Irei O. The configuration of the laminas and facet joints in degenerative spondylolisthesis. A clinicoradiologic study. Spine (Phila Pa 1976). 1989;14(11):1265-1271.
26. Matsunaga S, Sakou T, Morizono Y, Masuda A, Demirtas AM. Natural history of degenerative spondylolisthesis. Pathogenesis and natural course of the slippage. Spine (Phila Pa 1976). 1990;15(11):1204-1210.
27. Fry RW, Alamin TF, Voronov LI, et al. Compressive preload reduces segmental flexion instability after progressive destabilization of the lumbar spine. Spine (Phila Pa 1976). 2014;39(2):E74-81.
28. Gibson JN, Depreitere B, Pflugmacher R, et al. Decompression and paraspinous tension band: a novel treatment method for patients with lumbar spinal stenosis and degenerative spondylolisthesis. Spine J. 2015;15(3 Suppl):S23-32.
29. Jansen T, Bornemann R, Otten L, Sander K, Wirtz D, Pflugmacher R. [A Comparison of Dorsal Decompression and Dorsal Decompression Combined with the Dynamic Stabilisation Device LimiFlex]. Z Orthop Unfall. 2015.
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31. Davis R, Auerbach JD, Bae H, Errico TJ. Can low-grade spondylolisthesis be effectively treated by either coflex interlaminar stabilization or laminectomy and posterior spinal fusion? Two-year clinical and radiographic results from the randomized, prospective, multicenter US investigational device exemption trial: clinical article. J Neurosurg Spine. 2013;19(2):174-184.
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35. Keenan BT, Maislin G, Sunwoo BY, et al. Obstructive sleep apnoea treatment and fasting lipids: a comparative effectiveness study. Eur Respir J. 2014;44(2):405-414.
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2019-4001

General Information

How did you learn about the YODA Project?: Data Holder (Company)

Conflict of Interest

Request Clinical Trials

Associated Trial(s):
  1. NCT00316121 - A Prospective, Multicenter, Randomized Study Comparing the Use of HEALOS® to Autograft in a Transforaminal Lumbar Interbody Fusion (TLIF) Approach
What type of data are you looking for?: Individual Participant-Level Data, which includes Full CSR and all supporting documentation

Request Clinical Trials

Data Request Status

Status: Not Approved

Research Proposal

Project Title: LimiFlex Clinical Trial for the Treatment of Degenerative Spondylolisthesis With Spinal Stenosis

Scientific Abstract: Background: Degenerative spondylolisthesis (DS) with lumbar spinal stenosis (LSS) is commonly treated with decompression and fusion. Fusion has been shown to be effective, however is associated with significant morbidity and cost. The LimiFlex paraspinous tension band (PTB; Empirical Spine, San Carlos, CA) is an alternative stabilization technique for patients receiving surgical decompression for DS with LSS.
Objective: The objective of this multi-center study is to evaluate the safety and effectiveness of decompression and stabilization with the PTB compared to decompression and transforaminal lumbar interbody fusion (TLIF) with concomitant posterolateral fusion (PLF) for the treatment of DS with LSS.
Study Design: This is a multi-center, prospective, concurrently controlled, non-blinded study. Balance between groups will be achieved through sub classification using propensity scores.
Participants: The prospectively enrolled control group will be supplemented with retrospectively enrolled control subjects recruited from participating study sites, as well as subjects meeting inclusion criteria from the requested HEALOS study data.
Outcome Measures: Non-inferiority of the investigational group will be assessed with composite clinical success criteria including 15 point reduction of oswestry disability index, no new or worsening persistent neurologic deficit, and no device integrity failures.
Statistical Analysis: Non-inferiority will be assessed in a stratified analysis among propensity score-ranked quintiles.

Brief Project Background and Statement of Project Significance: Degenerative spondylolisthesis is a common clinical condition of the lumbar spine in which there is anterior translation of the superior vertebra relative to the inferior vertebra, with an intact neural arch and degenerative changes of the facet joints. It rarely occurs before the age of 50 years, and it disproportionately affects women, with a female:male ratio of 6:1. Degenerative spondylolisthesis is typically associated with degenerative changes which render the facet joints less resistant to shear forces borne by the segment.
Patients with degenerative spondylolisthesis typically present with symptoms of stenosis, which are relieved surgically with a decompression/laminectomy. Unfortunately, however, the removal of tissue involved in the decompression increases the flexion instability of the spinal segment, and, over time, the listhesis can increase and cause symptoms to recur. Although some studies report good results in patients who receive only a decompression, including two studies which suggest that more limited decompressions preserve sufficient stability without the need for fusion, most suggest that fusion of the segment after decompression provides clinical benefit. Recently, the results of a randomized clinical trial comparing decompressions alone to decompressions and fusion demonstrated that the increasing postoperative segmental flexion in patients with decompression was associated with increasing anterior translation and a poor clinical result. As a result of these findings, the predominant surgical approach in the United States is to treat degenerative spondylolisthesis patients with a decompression and fusion to ensure a good clinical outcome.
Decompression with instrumented fusion, while the standard of care, is still an invasive surgical option and not appropriate or desirable for many patients due to its complication rate and postoperative morbidity. Complications associated with implantation of fusion instrumentation are well understood: these include vascular injury, direct nerve root injury, or disruption of facet joints outside of the segment to be fused. The amount of dissection and retraction of the paraspinal musculature required during the fusion procedure is significantly increased relative to a decompression-alone to allow for the placement of pedicle screws and bone graft. Average blood loss and operative time for instrumented fusion have been reported to be over 600 ml and over 4 hours, respectively. In comparison, current decompression techniques have reported blood loss in the range of 30-50 ml and operative times of less than 2 hours. The additional operative time and exposure results in increased general peri-operative complications associated with their use, including cardiopulmonary complications and infection.
The PTB is designed to allow the surgeon to perform a decompression to treat the presenting symptoms and then apply the device to stabilize the segment. As such, it presents a new stabilization option for patients for whom a surgeon would like to add stability to a decompression without adding the potential risks, morbidity and complications of a fusion.

Specific Aims of the Project: The primary study objective is to demonstrate the safety and effectiveness of the PTB when used for spinal stabilization, at one level from L1 to S1, in skeletally mature patients following surgical decompression for treatment of lumbar degenerative spondylolisthesis (Grade I per Meyerding classification) with spinal stenosis.
The objective of the present data request is to supplement the control group with historically obtained data from qualifying subjects. Note that the original sponsor of the requested study has been contacted, is supportive of this request, and advised that the data should be requested through the YODA project.

Study Design:

What is the purpose of the analysis being proposed? Please select all that apply.:

Software Used: I am not analyzing participant-level data / plan to use another secure data sharing platform

Data Source and Inclusion/Exclusion Criteria to be used to define the patient sample for your study: Detailed Inclusion/Exclusion criteria are published for NCT03115983 on clinicaltrials.gov. Data sources will include prospective investigational and control subjects enrolled at participating study sites; retrospective control subjects included by participating study sites; and historical control patients from the requested YODA data set meeting inclusion/exclusion criteria.
Individual subject level data from the requested study will be screened for inclusion in the broader study. Only data from included subjects will be utilized. Note that the original sponsor of the requested study has been contacted, is supportive of this request, and advised that the data should be requested through the YODA project.

Primary and Secondary Outcome Measure(s) and how they will be categorized/defined for your study: The main outcome measures utilized in the primary endpoint include Oswestry Disability Index, neurologic exam results, reoperations/revisions, and radiographic device condition. Secondary outcome measures include the individual components of the primary endpoint, as well as Estimated blood loss, Length of procedure, Hospital stay, Return to normal activities of daily living, Work status, Pain medication including narcotics usage, Visual analog scale (VAS) leg pain, Visual analog scale (VAS) back pain, Zurich claudication questionnaire (ZCQ), SF-12 Quality of Life survey, Patient satisfaction and Radiographic fusion status.

Main Predictor/Independent Variable and how it will be categorized/defined for your study: The main predictor independent variable is a Composite Clinical Success (CCS) endpoint evaluated at 24 months follow-up that will assess individual success for patients in the investigational LimiFlex or control fusion arm . To be considered a success, a subject must demonstrate ALL of the following components of the CCS at 24 months:
- 15 point improvement in Oswestry Disability Index (100 point scale)
- Absence of a new or worsening, persistent neurological deficit
- Absence of additional surgical intervention
- Absence of device integrity failures

Other Variables of Interest that will be used in your analysis and how they will be categorized/defined for your study: Secondary outcomes include:
? Each of the individual components of the composite primary endpoint
? Estimated blood loss and units of blood transfused
? Length of procedure (skin to skin)
? Hospital stay
? Length of time for subject to return to his/her normal activities of daily living
? Work status and days to return to work (as appropriate)
? Medication use for pain, including narcotic usage
? Leg pain as measured on a Visual Analog Scale (VAS)
? Back pain as measured on a Visual Analog Scale (VAS)
? Zurich Claudication Questionnaire (ZCQ)
? Quality of Life through use of the SF-12 Health Survey
? Patient satisfaction
? Radiographic fusion status
Economic parameters will be collected to assess and compare the cost-effectiveness of the investigational and control procedures.

Statistical Analysis Plan: The treatment arm (LimiFlex Paraspinous Tension Band) is compared to a transforaminal lumbar interbody fusion with concomitant posterolateral fusion with pedicle screw instrumentation (control arm) following decompression. The primary effectiveness analysis is a responder analysis at 24-months post-operative where a subject is a responder if each of the following are satisfied:
? Function - Improvement of at least 15 points (of 100) on the Oswestry Disability Index (ODI) from baseline compared to 24 months
? Neurological status - Absence of a decrease in neurologic status (motor or sensory) at 24 months compared to baseline unless attributable to a concurrent medical condition or other cause unrelated to the device and/ or study procedure
? Surgical Intervention - Absence of additional surgical intervention, in a separate surgery subsequent to the index procedure, defined as revision, removal, reoperation or supplemental fixation/fusion at the instrumented level or levels adjacent to the instrumented level, over the initial 24 months
? Device Integrity - Absence of integrity failures, defined as device breakage, device separation or disassembly, or device dislocation over the initial 24 months
The primary non-inferiority test will be conducted based on statistically combining within propensity score (PS) subclass comparisons of Month 24 composite clinical success rates between device groups. To conduct the non-inferiority test, the lower bound of a PS subclass adjusted one-sided 95% confidence interval for the difference in success rates will be determined. If this lower bound is larger than -0.125 it will be concluded that the investigational device is clinically non-inferior to control in terms of Month 24 composite clinical success. If the non-inferiority is demonstrated in this way, the same lower bound will be compared to zero and if it exceeds zero, superiority will be claimed. By the closed testing principle, there is no multiplicity adjustment needed for this test of superiority.
Kaplan-Meier survival analysis will be used to characterize and compare failure time distributions between groups stratifying on propensity score quintile where failures include device failure, revisions, reoperations, removals or supplemental fixations for each treatment group. Logistic regression analysis will be used to assess potential factors associated with success or failure of the investigational device including age, gender, BMI, and baseline ODI. Descriptive analyses of continuous secondary endpoints and other relevant variables will include computation of device group specific descriptive statistics including means, standard deviations, medians, minimum, and maximum values. Categorical variables will be summarized using counts and percentages. Specific adverse events and classes of adverse events (e.g., device-related, serious, severity) will be summarized according to the total number of events occurring as well as according to subject specific incidence rates. Counts of the numbers of specific events occurring during discrete time intervals over time and according to severity will be tabulated by device group. Device group differences in classes of adverse events will be summarized using PS subclass adjusted normal distribution based 95% confidence intervals when there are sufficient data to permit this type of analysis. Specific adverse event rates will be summarized using exact 95% confidence intervals for the difference in two binomials but will not account for PS subclass.
As described above, there may be as many as three sources of controls, prospective concurrent controls, retrospective controls, and historical controls or LimiFlex subjects. Primary and secondary effectiveness endpoints will be compared among investigational device subjects, prospective concurrent controls, retrospective controls, and historical controls or LimiFlex subjects, depending upon the number of sources utilized.

Narrative Summary: The LimiFlex? Clinical Trial is a prospective, concurrently controlled, multi-center study to evaluate the safety and effectiveness of decompression and stabilization with the Empirical Spine LimiFlex? Paraspinous Tension Band compared to decompression and transforaminal lumbar interbody fusion (TLIF) with concomitant posterolateral fusion (PLF) for the treatment of lumbar degenerative spondylolisthesis (Grade I per Meyerding classification) with spinal stenosis. The objective of this data request is to supplement the control group with historically obtained data from qualifying subjects. Note that the original sponsor of the requested study is supportive of this request.

Project Timeline: Enrollment complete: End of 2019
Primary endpoint completion: End of 2021
Primary analysis complete and FDA submission: 2022
Primary manuscript and results posted to YODA: 2023
Final report (with 5-year follow-up, beyond primary endpoint): 2025

Dissemination Plan: Several manuscripts are expected from this study: primary and secondary clinical outcomes; economic cost-effectiveness studies; radiographic outcomes; and long-term (beyond primary endpoint) clinical, radiographic and economic outcomes. Target journals, ranked by priority, are as follows:
- The Spine Journal [Spine J]
- Spine [Spine (Phila Pa 1976)]
- The Journal of Neurosurgery: Spine [J Neurosurg Spine]
- Journal of Bone and Joint Surgery [J Bone Joint Surg Am]
- International Journal of Spine Surgery [Int J Spine Surg]

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