← Product Code NQO · P240043 # DIAM­™ Spinal Stabilization System (P240043) _Companion Spine France Sas · NQO · Dec 10, 2025 · Orthopedic · APPR_ **Canonical URL:** https://fda.innolitics.com/device/P240043 ## Device Facts - **Applicant:** Companion Spine France Sas - **Product Code:** NQO - **Decision Date:** Dec 10, 2025 - **Decision:** APPR - **Device Class:** Class 3 - **Review Panel:** Orthopedic - **Attributes:** Therapeutic ## Intended Use The DIAM™ Spinal Stabilization System is indicated for skeletally mature patients that have moderate to severe primary low back pain (greater than leg pain) secondary to lumbar degenerative disc disease (DDD), at a single level from L2-L5 with current episode refractory to at least 6 months non-operative care. Symptomatic disc disease is confirmed by patient history, physical examination, and radiographic evaluation with one or more of the following factors: - Greater than 2mm of decreased disc height (average disc height) compared to the adjacent level - Scarring/thickening of the ligamentum flavum, annulus fibrosus, or facet joint capsule - Non-extruded herniated nucleus pulposus. The DIAM™ device is implanted via a minimally invasive posterior approach. ## Device Story The DIAM™ Spinal Stabilization System is an interspinous spacer designed to load-share with the posterior disc and facet joints to relieve low back pain while preserving motion. The device is implanted via a minimally invasive posterior approach by a surgeon. It consists of an H-shaped silicone core (NuSil MED 4765) jacketed in high-tenacity polyethylene terephthalate (PET) fabric, secured by PET tethers and Grade 2 titanium crimps. The spacer is placed between adjacent spinous processes; tethers are looped around the processes and locked with crimps using a crimper tool. By providing mechanical stabilization, the device reduces flexion-extension range of motion at the index level. Healthcare providers evaluate patient outcomes via ODI, NRS pain scores, and radiographic assessment. The device benefits patients by providing a non-fusion surgical alternative for discogenic pain, potentially delaying more invasive procedures like fusion or total disc replacement. ## Clinical Evidence PMA approval based on a prospective, multicenter, randomized controlled IDE trial (G050025) comparing DIAM™ to non-operative care (n=283). Primary endpoint: composite clinical success (ODI improvement ≥15 points, no implant-associated SAEs, no secondary surgical interventions) at 24 months. Results: 67.4% success in DIAM™ cohort vs 11.9% in control (BPPmITT population). Supplemental long-term follow-up (LTFU) study (n=116) evaluated patients at mean 11.5 years, showing durable improvements in ODI and NRS scores. Safety data included AE/SAE rates, spinous process fracture incidence, and secondary surgical intervention rates, which were comparable to other approved interspinous devices. ## Technological Characteristics Interspinous spacer system; H-shaped configuration. Materials: Silicone core (NuSil MED 4765), high-tenacity PET fabric jacket, Grade 2 commercially pure titanium crimps. Sizes: 8, 10, 12, 14 mm. Mechanical stabilization via load-sharing; posterior surgical approach. MR compatible (1.5T/3T). Sterilization: Not specified. Connectivity: None (mechanical implant). ## Regulatory Identification This device is an interspinous spacer or spinous process plate that is implanted between the spinous processes or attached to the spinous process. ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) ## I. GENERAL INFORMATION Device Generic Name: Prosthesis, Spinous Process Spacer/Plate Device Trade Name: DIAM™ Spinal Stabilization System Device Product Code: NQO Applicant’s Name and Address: Companion Spine Etage 5 – 4 Allée des Acacias Mérignac 33 700 France Date of Panel Recommendation: None Premarket Approval Application: P240043 (PMA Number) Date Of FDA Notice of Approval: December 10, 2025 Breakthrough Device: Granted breakthrough device status on October 5, 2021, because the device and proposed indication for use met the program criteria. ## II. INDICATIONS FOR USE The DIAM™ Spinal Stabilization System is indicated for skeletally mature patients that have moderate to severe primary low back pain (greater than leg pain) secondary to lumbar degenerative disc disease (DDD), at a single level from L2-L5 with current episode refractory to at least 6 months non-operative care. Symptomatic disc disease is confirmed by patient history, physical examination, and radiographic evaluation with one or more of the following factors: - Greater than 2mm of decreased disc height (average disc height) compared to the adjacent level - Scarring/thickening of the ligamentum flavum, annulus fibrosus, or facet joint capsule - Non-extruded herniated nucleus pulposus The DIAM™ device is implanted via a minimally invasive posterior approach. PMA P240043: FDA Summary of Safety and Effectiveness Data Page 1 of 65 {1} III. CONTRAINDICATIONS The DIAM™ Spinal Stabilization System is contraindicated in patients with: - An allergy to silicone, polyethylene terephthalate, or titanium; - Spinal anatomy or disease that would prevent implantation of the device or cause the device to be unstable in situ, such as: Instability of the lumbar spine, e.g., isthmic spondylolisthesis or degenerative spondylolisthesis (anterolisthesis with more than 2mm of translation) or retrolisthesis at the involved level; - Disc height loss greater than 67% (average disc height) at the involved level compared to the next adjacent spinal level; - Scoliosis (Cobb angle greater than 10 degrees), flat back, or kyphotic spine at the operative level; - Severe anatomical alterations at the operative levels including congenital abnormalities, spinal tumor, or evidence of prior or existing lumbar spine trauma; - Prior surgery at operative level; - Cauda equina syndrome defined as neural compression causing neurogenic bladder or bowel dysfunction; - Disc degeneration requiring treatment at more than one lumbar level; - Extruded or sequestered disc herniations; - Large osteophytes and/or severe hypertrophy between the vertebral bodies and/or the facet articular process with or without severe subarticular bone erosions and/or subchondral cysts; - Diagnosis of osteoporosis, defined as a DEXA bone mineral density T-score equal to or less than -2.5; - Pregnancy; - Active systemic infection, or infection localized to the site of implantation; - Morbid obesity defined as body mass index (BMI) greater than 40. IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the DIAM™ Spinal Stabilization System Physician labeling. V. DEVICE DESCRIPTION DIAM™ Spinal Stabilization System is an interspinous spacer implanted between adjacent spinous processes using a posterior surgical approach. The DIAM™ device is designed to load-share with the posterior disc and facet joints that are overloaded due to disc degeneration, thereby relieving low back pain while preserving motion at the treated spinal level. The DIAM™ Spinal Stabilization System implant consists of 3 main components: the H-shaped interspinous process spacer, the spinous process tethers, and the crimps. The spacer PMA P240043: FDA Summary of Safety and Effectiveness Data Page 2 of 65 {2} is implanted between two adjacent spinous processes, each tether is looped around a spinous process, and the crimps are used to secure the ends of the tethers. Each spacer is packaged with two tethers and two crimps. The DIAM™ Spinal Stabilization System is packaged with the tethers preloaded into the spacer. The spacer component is manufactured from a core of silicone (NuSil MED 4765) and is covered by a fabric knitted jacket of high tenacity polyester (Polyethylene Terephthalate, or PET). The spacer is in an “H”-shaped configuration with the wings of the “H” extending on each side of the spinous processes between which it is placed. The tethers are manufactured from PET fibers that are the same material as the woven spacer jacket. A small, open “eye” is spliced into one end of each tether, and a curved needle is crimped onto the other end. The curved needle is used for passage of the tether around the spinous process. It is then passed through the eye-end of the tether to form a complete loop and secure the construct to the spinous process. The crimp is used to secure the tether loop. The crimp is manufactured from Grade 2 commercially pure titanium. The crimp is locked in place by compressing its diameter using a crimper tool similar to a pair of pliers. A visual representation of the DIAM™ Spinal Stabilization System and its components are shown below in Figure 1. ![img-0.jpeg](img-0.jpeg) Figure 1: Components of the DIAM™ Spinal Stabilization System Implant The DIAM™ Spinal Stabilization System is offered in 4 sizes: 8, 10, 12, and 14 mm. These sizes correspond to the height of the spacer portion of the device that is placed between the spinous processes. The tethers and crimps remain the same regardless of the spacer size. The available catalog sizes for the DIAM™ Spinal Stabilization System are listed in Table 1. PMA P240043: FDA Summary of Safety and Effectiveness Data {3} Table 1: DIAM™ Spinal Stabilization System Device Sizes | Catalog Number | Description | | --- | --- | | CS001A0008 | 8 mm DIAM™ Spinal Stabilization Device | | CS001A0010 | 10 mm DIAM™ Spinal Stabilization Device | | CS001A0012 | 12 mm DIAM™ Spinal Stabilization Device | | CS001A0014 | 14 mm DIAM™ Spinal Stabilization Device | ## VI. ALTERNATE PRACTICES AND PROCEDURES There are several other alternatives for the treatment of primary low back pain secondary to lumbar DDD, which is a multi-factorial and often nonreversible pathologic condition. Non-surgical alternatives include, but are not limited to, patient education, prescribed medications, physical therapy, spinal injections, braces, exercise programs, or rest. Surgical alternatives include, but are not limited to, fusion using various bone grafting techniques and devices (including but not limited to interbody fusion devices and posterior pedicle screw/rod systems), or non-fusion surgeries such as lumbar total disc replacement devices. The DIAM™ Spinal Stabilization System is intended to treat subjects with primary discogenic low back pain requiring treatment at a single level (L2-L5) who are not yet suitable candidates for more invasive treatments including lumbar total disc replacement (TDR) or lumbar fusion. Each treatment option has advantages and disadvantages. Patients should fully discuss the available alternatives with his or her physician to select the option that best meets their clinical condition, lifestyle and expectations. ## VII. MARKETING HISTORY The DIAM™ Spinal Stabilization System has been marketed outside the United States since 1998. The device is currently distributed on five continents, in countries/regions including but not limited to, Brazil, Canada, European Union, Korea, and Mexico. The DIAM™ Spinal Stabilization System has not been withdrawn from distribution/ marketing in any country for safety or effectiveness reasons. ## VIII. POTENTIAL ADVERSE EVENTS Below is a list of the potential adverse events (i.e., complications) identified from the DIAM™ Spinal Stabilization System clinical study results, approved device labeling for other interspinous devices, published literature, and international post-marketing data including: 1) those associated with any surgical procedure; 2) those potentially associated with lumbar spinal surgery using a posterior approach; and, 3) those potentially associated with lumbar spinal implants and, in particular, with interspinous devices including the DIAM™ Spinal Stabilization System. In addition to the risks listed below, there is also the risk that the procedure may not be effective in relieving symptoms and may cause PMA P240043: FDA Summary of Safety and Effectiveness Data {4} worsening of symptoms. Additional surgery may be required to correct some of the adverse effects. ## Risks Associated with any Surgical Procedure General surgical risks include, but are not limited to: - Anesthesia complications including allergic reaction, anaphylaxis, or other reactions to anesthesia - Anemia - Blood loss/hemorrhage possibly requiring a blood transfusion with possible transfusion reaction - Myocardial infarction - Blood clots including pulmonary emboli - Phlebitis - Injury to blood vessels - Septicemia - Cerebral Vascular Accident (i.e., stroke) - Pulmonary complications including atelectasis, pneumothorax or pneumonia, pulmonary edema and respiratory distress - False aneurysm - Infection (wound, local, and/or systemic) abscess, or cellulitis, localized or systemic, fever - Soft tissue damage or fluid collections, including edema, hematoma or seroma, which may require drainage, aspiration, or debridement or other intervention - Surgical wound dehiscence, necrosis, or scarring of tissue around the wound - Impairment of the gastrointestinal system including ileus or bowel obstruction, nausea or vomiting - Impairment of the genitourinary system including incontinence, bladder dysfunction, urinary tract infection, or reproductive system complications - Neurological complications including nerve damage, paralysis, seizures or convulsions, changes to mental status, or reflex sympathetic dystrophy - Numbness - Complications of pregnancy including miscarriage or congenital defects - Pain at surgical site - Death ## Risks Associated with Lumbar Spine Surgery Risks associated with lumbar spine surgery include, but are not limited to: - Risks to neurological structures: - Dural tear, dural leak and/or dural injury with or without CSF leakage - Arachnoiditis - Neurologic deterioration - injury to nerves or nerve roots associated with the spinal cord (resulting in pain, weakness, paralysis (partial or complete), paresthesia, altered reflexes, numbness, tingling, or other changes in sensation) - Gait disturbance PMA P240043: FDA Summary of Safety and Effectiveness Data Page 5 of 65 {5} ○ Cerebrospinal fluid leakage ○ Cerebrospinal fistula ○ Reflex Sympathetic Dystrophy (RSD) - New or worsened back or leg pain - Damage to nerves, blood vessels, and nearby tissues - Impaired muscle or nerve function - Epidural bleeding, hematoma, or fibrosis - Surgery at incorrect levels - Osteolysis - Loss of bowel or bladder function - Fracture of the vertebrae, spinous process, or other damage to bony structures during or after surgery - Postoperative muscle and tissue pain - Development of degenerative changes at adjacent levels - Scarring or soft tissue damage - Spinal instability - Post-surgical spondylolisthesis (vertebral slippage) - Retrolisthesis - Spinal stenosis (narrowing of the spinal canal) - Spondylosis - Infection of the bone, or surrounding soft tissue - Perineural fibrosis - Pain and discomfort associated with the presence of implants - Pain and discomfort associated with the surgical procedure (e.g., cutting of muscles, ligaments, and tissue) and healing - The spine may undergo adverse changes or deterioration including loss of proper spinal curvature, correction, height, and/or reduction, or malalignment, and another surgery may be required - Adverse bone/implant interface reaction - Instruments breaking or malfunctioning which may cause damage to the operative site or adjacent structures ## Risks Associated with Lumbar Spine Implants (including the DIAM™ Spinal Stabilization System) Risks associated with lumbar spine implants such as DIAM™ Spinal Stabilization System include, but are not limited to: - Sensitivity or allergy to the implant material [Polyethylene Terephthalate (PET), silicone, and titanium] - Failure of the device/procedure to improve symptoms and/or function - Pain and discomfort associated with the operative site or presence of implants - Implant malposition or incorrect orientation PMA P240043: FDA Summary of Safety and Effectiveness Data Page 6 of 65 {6} - Sizing issues with components - Uncrimping of the needle instrument leading to increased operation time - Anatomical or technical difficulties implanting the device - Spinous process fracture - Spinous process bone resorption - Bone loss or decrease in bone density, possibly caused by stress shielding - Production of wear debris which may damage surrounding soft tissues including muscle or nerve - Foreign body reaction to implant material or material debris and/or autoimmune disease - Deep infection - Formation of scar tissue at implant site - Implantation at the wrong spinal level - Migration or dislodgement of the implant from the original position so that it becomes ineffective or causes damage to adjacent bone or soft tissues including nerves - Reoperation including revision, removal, or supplemental fixation - Loosening, fatigue, deformation, breakage or disassembly of the implant, which may require another operation to remove the implant and may require another treatment method. For the specific adverse events (AEs) that occurred in the clinical study, please see Section X below. ## IX. SUMMARY OF NON-CLINICAL STUDIES Several non-clinical tests were conducted to characterize the performance of the DIAM™ Spinal Stabilization System. Where relevant, all tests were performed using finished components, devices, or representative test specimens manufactured in accordance with current specifications. The non-clinical tests are outlined below. ### A. Laboratory Studies The laboratory studies conducted are listed below. Table 2 provides further details on methods, acceptance criteria, and results. - Static Axial Compression - Static Compressive Creep - Axial Compression Fatigue - Static Tension - Tension Fatigue - Static and Fatigue Testing of Accelerated Aged DIAM™ Devices - Rotational Fatigue - Axial Grip - Wear Debris Analysis PMA P240043: FDA Summary of Safety and Effectiveness Data Page 7 of 65 {7} Biomechanical Evaluation Table 2: Laboratory Studies on DIAM™ Spinal Stabilization System | Test | Methods | Acceptance Criteria | Results | | --- | --- | --- | --- | | Static Axial Compression | Six samples of the smallest (8 mm) DIAM™ implant were tested under static axial compression loading between metallic test fixtures intended to mimic the geometry of spinous processes. Testing was performed under a displacement rate of 25 mm/min until just before fixture-to-fixture contact was reached at which time the peak load required to achieve this displacement was recorded. | Maximum compressive strength should exceed expected in vivo spinous process fracture load of 339 N¹. | Average peak load achieved was 2199 ± 82.6 N, which was greater than the acceptance criterion. No damage to the devices was observed during testing. Average device stiffness observed between 0 N and 500 N (clinically relevant loading range) was 76.3 ± 9.8 N/mm. There was no acceptance criterion associated with device stiffness. | | Static Compressive Creep | Compressive creep was measured by applying a range of physiological compressive loads (270 N, 360 N, 450 N) were applied to the worst-case (8 mm) DIAM™ device to quantify the strain observed on the device. Three DIAM™ devices were tested under the static loads listed above (n=1 for each load) in phosphate buffered saline at 37°C. Static loads were applied for 1000 hours. | The max % strain for each static load level shall be below the failure limit of 90%. The % strain vs. time should exhibit a projection toward an asymptotic strain steady state. The % strain at the projected steady state should be below the failure limit of 90%. | The maximum % strains and steady state strains for all three (n=3) static load levels were below the acceptance criteria of 90%. 270 N – 16.2% strain 360 N – 15.0% strain 450 N – 16.1% strain | | Axial Compressive Fatigue | Six samples of the smallest (8 mm) and thirteen samples of the largest (14 mm) DIAM™ device were subjected to dynamic axial compression loading between metallic test fixtures intended to mimic the geometry of the spinous processes. Testing | Two samples of each device size should run out to 10 MC at a load level equal to or above the expected in vivo spinous process fracture load of 339 N¹ without failure. | Two 8 mm devices ran out to 10 MC at 480N Two 14 mm devices ran out to 10 MC at 500 N. The acceptance criterion was exceeded for both device sizes. | PMA P240043: FDA Summary of Safety and Effectiveness Data {8} PMA P240043: FDA Summary of Safety and Effectiveness Data Page 9 of 65 | Test | Methods | Acceptance Criteria | Results | | --- | --- | --- | --- | | | was conducted in phosphate buffered saline at 37°C at 8 Hz with R=10 to 10 million cycles (MC) or device failure. | | Wear of the outer PET sheath at the fixture contact point was observed for non-runouts. | | Gravimetric Wear Debris Analysis | Gravimetric wear analysis was performed on devices that achieved dynamic axial compression loading to 10 MC. | This evaluation was performed for characterization purposes only. | For the largest runout loads at each size, the average decrease in weight was 0.18% for the small (8 mm) and 0.26% for the large (14 mm) implants. | | Wear Debris Analysis (Axial Compression Fatigue Samples) | A particle analysis per ASTM F1877 was performed on wear debris from the DIAM™ device collected in the saline bath after axial compression fatigue testing. | This test was performed in order to characterize the particulate wear debris generated by the DIAM™ device. No specific acceptance criteria are associated with this evaluation. | The compositions of the particles were polymeric-based, consistent with PET, and Silicone. The average size of particles in the sample was 1.24 microns in diameter using SEM analysis. The particles were generally oval in shape with an average aspect ratio of 1.9. | | Static Tension | Six samples of the smallest (8 mm) DIAM™ device were subjected to static tension loading after attachment to metallic test blocks intended to mimic the geometry of the spinous processes. Tensile loading was applied in displacement control at a rate of 25 mm/min until failure. Testing was conducted in phosphate buffered saline at 37°C. | Maximum compressive strength should exceed expected in vivo spinous process fracture load of 339 N^{1}. | Average peak load achieved was 401 ± 50 N. All samples exceeded the acceptance criterion. Failure mode for all devices was slippage of one or both tethers. | | Tension Fatigue | Six samples of the smallest (8 mm) DIAM™ device were subjected to dynamic tension loading after attachment to metallic test fixtures intended to mimic the geometry of the spinous processes. Testing was | The DIAM™ device must be able to withstand a tensile fatigue load of 100 N to 10 MC. | Two devices ran out to 10 MC at 155 N without any visual failures. Tether detachment from the spacer was the failure mode for non-runouts. | {9} PMA P240043: FDA Summary of Safety and Effectiveness Data Page 10 of 65 | Test | Methods | Acceptance Criteria | Results | | --- | --- | --- | --- | | | conducted in phosphate buffered saline at 37°C at 8 Hz with R=10 to 10 MC or device failure. | | | | Static Axial Compression (10Yr Accelerated Aged Implants) | Five accelerated aged samples of the smallest (8 mm) DIAM™ implant were tested under static axial compression loading between metallic test fixtures intended to mimic the geometry of spinous processes. Testing was performed in phosphate buffered saline at 37°C under a displacement rate of 25 mm/min until just before fixture-to-fixture contact was reached at which time the peak load required to achieve this displacement was recorded. | The mean static compression stiffness must be sufficiently equivalent to previous testing of unaged DIAM™ samples. | The average static axial compression stiffness was 77.6 ± 3.8 N/mm which was considered sufficiently equivalent to previous testing of unaged DIAM™ devices. | | Axial Compression Fatigue (10Yr Accelerated Aged Implants) | Seven accelerated aged samples of the smallest (8 mm) DIAM™ device were subjected to dynamic axial compression loading between metallic test fixtures intended to mimic the geometry of the spinous processes. Testing was conducted in phosphate buffered saline at 37°C at 8 Hz with R=10 to 10 MC or device failure. | Two samples should run out to 10 MC at a load level equal to or above the expected *in vivo* spinous process fracture load of 339 N^{1} without failure. | Two compressive fatigue runouts were achieved at 360 N which exceeds the acceptance criterion. Tearing of the outer sheath was the failure mode for non-runouts. | | Tension Fatigue (10Yr Accelerated Aged Implants) | Three accelerated aged samples of the smallest (8 mm) DIAM™ device were subjected to dynamic tension loading after attachment to metallic fixtures intended to mimic the geometry of the spinous processes. Testing was conducted in | The tensile fatigue runout load must be equal to or exceed a load of 100 N. | Two tensile fatigue runouts were achieved at the required load of 100 N. Tether breakage was the failure mode for the non-runout. | {10} PMA P240043: FDA Summary of Safety and Effectiveness Data Page 11 of 65 | Test | Methods | Acceptance Criteria | Results | | --- | --- | --- | --- | | | phosphate buffered saline at 37°C at 8 Hz with R=10 to 10 MC or device failure. | | | | Rotational Fatigue | Two samples of the smallest (8 mm) DIAM™ device were tested in rotational fatigue testing which was adapted from ASTM F2077. Testing was conducted in phosphate buffered saline at 37°C. A 150 N compressive load was applied to each sample while the superior fixture was rotated ± 3° at a rate of 8 Hz until 10 MC were reached or failure of the device occurred. | The devices shall achieve runouts to 10 MC of axial rotation ± 3° and a compressive load of 150 N without exhibiting gross implant failure. | The two samples reached 10 MC under the conditions described without experiencing gross failure. Minor damage was observed on the device sheath at the fixture contact point. | | Axial Grip (Tether and Crimp) | Five flat tethers and crimps of the DIAM™ device were tested in isolation from the core under tensile loading to determine the force necessary for the tether to slip in the crimp. Testing was conducted in displacement control at 0.25 mm/sec in ambient lab conditions. | The static axial grip strength of the crimp on the flat tether must be sufficiently equivalent or greater than the axial grip strength of the crimp on round tethers of the previous DIAM™ design. | The average static axial grip strength of the crimp on the flat tethers was 91.6 ± 35.5 N. This result was sufficiently equivalent to the static axial grip strength of the crimp on the round tether. | | Static Tension (Tether Only) | Five flat tethers of the DIAM™ device were tested under static tension loading in isolation from the core. Testing was conducted in displacement control at 0.25 mm/sec in ambient lab conditions. | The static tensile strength of the flat tether must be sufficiently equivalent or greater than the strength of the round tethers of the previous DIAM™ design. | The average static tensile strength of the flat tethers was 526.86 ± 48.47 N. This result exceeded the static tensile strength of the round tether. | | Wear Debris Analysis (Explants) | Wear debris from the explanted DIAM™ devices was characterized in accordance with ASTM F1877. | This test was performed in order to characterize the particulate wear debris generated by the DIAM™ device. No specific | Wear particulate characterization was consistent with prior in vitro and in vivo evaluations. | {11} | Test | Methods | Acceptance Criteria | Results | | --- | --- | --- | --- | | | | acceptance criteria are associated with this evaluation. | | | Biomechanics | Six male cadaveric lumbar spine specimens (L1 – sacrum) were implanted with a DIAM™ device at L4-L5. Range of motion (ROM) data were collected at L3/L4, L4/L5 and L5/S1 (index and adjacent levels) in flexion-extension (±6 Nm) with and without a 450 N static pre-load (follower load), lateral bending (±5 Nm) without a follower load, and axial rotation (±4 Nm) without a follower load. The above ROM measurements were made in four conditions: intact spine, after facetectomy at L4-L5, after discectomy at L4-L5, and after DIAM™ implantation at L4-L5 (after facetectomy and discectomy). | This study was performed to characterize the stabilizing effects of the DIAM™ implant in each of the three standard directions of rotation (flexion-extension, lateral bending, and axial rotation). No specific acceptance criteria were associated with this evaluation. | The study showed reduction of flexion-extension ROM (with and without follower load) at L4-L5 after DIAM™ implantation as compared to the intact and destabilized conditions. Lateral bending and axial rotation ROM were not significantly impacted by implantation of the DIAM as compared to the intact and destabilized conditions. Implantation of DIAM™ appeared to have minimal impact on ROM measurements at adjacent levels. | Shepherd, Duncan ET, et al. "Spinous process strength." Spine 25.3 (2000): 319-323. # B. Animal Studies The following animal studies were conducted: Rabbit Wear Debris Study - Sheep Implantation Study Details on the studies are provided below. # Evaluation of Local and Systemic Effects of Wear Debris Particulate from DIAM™ Following Implantation in Rabbits An in vivo study was performed to evaluate local and systemic responses to implantation of particulate wear debris from the DIAM™ Spinal Stabilization System in the lumbar spine of New Zealand White Rabbits. The animals were sacrificed at 3- and 6-month timepoints. The test article utilized was wear particles composed of the PET woven fabric jacket and silicone core of the DIAM™ implant. Evaluations included clinical and PMA P240043: FDA Summary of Safety and Effectiveness Data {12} neurological observations, hematology, serum chemistry, and gross pathology and histopathology of the implantation sites and organs. The test article wear debris was classified as a slight irritant as compared to the sham control at each timepoint. Interspinous implantation of the test article for three (3) and six (6) months resulted in inflammation that reached a steady state of biological response by the 6-month timepoint. There were no indications of systemic toxicity, and no systemic presence of test article wear debris. # Biocompatibility Evaluation of DIAM™ Spinal Stabilization System Using Sheep Model An in vivo study was performed to evaluate the long-term interactions between the materials of the DIAM™ implant and the interspinous process tissues. The DIAM™ test article was implanted in the lumbar spine of adult sheep. The animals were sacrificed at 6- and 12-month timepoints. Evaluations included clinical observations and gross pathology and histopathology of the implantation sites and organs. There were no wound infections and there were no neurological symptoms associated with the surgery. At necropsy, there were no signs of gross tissue reaction surrounding the implants. Histopathology showed chronic reactive fibrosis around the implant and vertebral spinous processes, as well as reactive changes in the sub-lumbar lymph nodes with no foreign implant material found. There were no changes in major organs that were associated with the implant. # C. Additional Studies Additional studies conducted are listed below. Table 3 provides further details on the methods and results. MR Compatibility Biocompatibility/Toxicity Device Sterilization - Packaging/Shelf-Life Validation Table 3: Additional Non-Clinical Studies on the DIAM™ Device | Test | Methods and Results | | --- | --- | | Biocompatibility | Biocompatibility evaluations for the DIAM™ Spinal Stabilization System were conducted based on the FDA guidance, “Use of International Standard ISO 10993-1, ‘Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process.’” Testing was designed to evaluate the device’s cytotoxicity, irritation, sensitization, acute systemic toxicity, sub-chronic toxicity, chronic toxicity, material mediated pyrogenicity, genotoxicity (bacterial reverse mutation, mammalian chromosomal aberration, and mouse bone marrow micronucleus), implantation, and carcinogenicity. Alternative assessments or testing methods (per ISO 10993) were utilized where appropriate. | PMA P240043: FDA Summary of Safety and Effectiveness Data Page 13 of 65 {13} Table 4: MR Compatibility Conditions | Static Magnetic Field Strength (B0) | 1.5T or 3T | | --- | --- | | Maximum Spatial Field Gradient | 30 T/m (3000 Gauss/cm) | | RF Excitation | Circularly polarized (CP) | | RF Transmit Coil Type | Integrated whole body transmit/ Receive coil | | Operating Mode | Normal or first level controlled operating mode | | Maximum Whole-Body SAR | 4 W/kg | | Scan Duration | 4 W/kg whole-body average SAR for 60 minutes of continuous RF (a sequence or back-to-back series/ scan without breaks). | | Scan Region | Any landmark is acceptable | | MR Image Artifact | The maximum artifact beyond the implant was 5 mm for the spin echo sequence and 9 mm for the gradient echo sequence in a 3-Tesla MR system (GE Signa HDxt MR System). Therefore, optimization of MR imaging parameters to compensate for the presence of this device may be necessary. The presence of other implants or the health state of the patient may require a modification of the MR conditions. | | During an MRI, the patient may notice a warming sensation around the implant or feel a tingling sensation. If the warming or tingling sensation is uncomfortable the patient should communicate this to the MR technologist, the MRI should be stopped, and the settings adjusted to reduce or eliminate the sensation. The highest temperature change above the background observed in non-clinical testing was +3.2°C (associated with specific conditions listed above). | | PMA P240043: FDA Summary of Safety and Effectiveness Data {14} If information about a specific parameter is not included, there are no conditions associated with that parameter. ## X. SUMMARY OF PRIMARY CLINICAL STUDY A clinical study was conducted to establish a reasonable assurance of safety and effectiveness of the DIAM™ Spinal Stabilization System for treatment of primary low back pain at a symptomatic, single level (L2-L5) in the US under Investigational Device Exemption (IDE) G050025. Data from this clinical study were the basis for the PMA approval decision. This primary dataset was supplemented with data provided from a long-term follow-up (LTFU) study, ‘DIAM™ Spinal Stabilization System Long Term Follow Up Clinical Plan’ (NCT 05201573). The goal of this additional study was to collect LTFU data on subjects who participated in the DIAM™ Spinal Stabilization System IDE Study and received the investigational device. A large cohort of subjects treated with the investigational device during the IDE study were evaluated at a mean final follow-up of 11.5 years. A summary of the clinical study conducted under G050025 is presented directly below. A summary of data collected in the LTFU study is presented in Section XII. ## A. Study Design Subjects were treated between 2007 and 2014. The database for this PMA reflected data collected through 2018 and included 283 subjects. The study was a prospective, multicenter, open label, randomized, controlled clinical trial comparing the DIAM™ Spinal Stabilization System to a control group of subjects treated with non-operative care. Subjects were randomized in a ratio of 2:1 to receive either surgical implantation of the investigational DIAM™ Spinal Stabilization System or non-operative care (control group). The control group received an individualized non-operative regimen of standard of care treatments tailored specifically to each individual subject’s needs. Non-operative care included patient education, as well as physical therapy, spinal injections, and medications. Control subjects were permitted to cross over to surgical treatment with the DIAM™ Spinal Stabilization System after 6-months of follow-up if their Oswestry Disability Index (ODI) score remained above 30, and a 15-point improvement in ODI was not achieved from baseline. ### 1. Clinical Inclusion and Exclusion Criteria Enrollment in this clinical study was limited to subjects that met the following inclusion criteria: - Has moderate low back pain secondary to lumbar degenerative disc disease at a single level from L2-L5. Low back pain is defined as persistent back pain, with or without radicular pain, with current episode of less than one year duration. Degenerative disc disease is confirmed by patient history, physical examination, and radiographic studies PMA P240043: FDA Summary of Safety and Effectiveness Data Page 15 of 65 {15} with one or more of the following factors (as measured radiographically by MRI scans or x-rays): ○ Decreased disc height >2mm, compared to the disc space at the next adjacent (superior or inferior, whichever has greater disc height) spinal level; ○ Scarring/thickening of the ligamentum flavum, annulus fibrosis, or facet joint capsule; ○ Herniated nucleus pulposus. - Is 18-70 years of age, inclusive, and is skeletally mature. - Has pre-treatment ODI score ≥ 30. - Has pre-treatment back Numerical Rating Scale (NRS) pain score of ≥ 8 based on the Pre-Treatment Back and Leg Pain Questionnaire (Back Pain Intensity + Back Pain Frequency). - Has been treated non-operatively (e.g., bed rest, physical therapy, medications, TENS, manipulation, and/or spinal injections) within a period of at least 6 weeks and not more than 6 months prior to enrollment in the clinical study. - If of child-bearing potential, patient is not pregnant or nursing and agrees not to become pregnant during the study period. - Is willing and able to participate in either of the randomized treatments for the duration of the study follow-up period. If the patient is randomized to the investigational group, he/she is willing to undergo surgery and receive the DIAM™ device. If the patient is randomized to the control group, he/she is willing to undergo all four non-operative treatments. - Is willing and able to comply with the study plan and able to understand and sign the Patient Informed Consent Form. Subjects were not permitted to enroll in this clinical study if they met any of the following exclusion criteria: - Has disc height loss > 67% at the involved level, compared to the next adjacent (superior or inferior, whichever has greater disc height) spinal level. - Has arachnoiditis. - Has a primary diagnosis of a spinal disorder other than degenerative disc disease at the involved level. - Requires treatment of degenerative disc disease at more than one lumbar level. - Has had all of the following non-operative treatments (prescribed medications, active physical therapy, spinal injections, and patient education) within the past 6 weeks. - Has a sequestered herniated nucleus pulposus. - Has had any previous surgery at the involved or adjacent spinal levels (including procedures such as a rhizotomy). - Has received any intradiscal ablation therapy, such as intradiscal electrothermal therapy (IDET). - Has congenital or iatrogenic posterior element insufficiency (e.g., facet resection, spondylolysis, pars fracture, or spinal bifida occulta). PMA P240043: FDA Summary of Safety and Effectiveness Data Page 16 of 65 {16} - Has back pain (with or without leg, buttock, or groin pain) that is not alleviated in any spinal position. - Has a motor deficit of the lower extremity. - Has cauda equina syndrome. - Has compression of nerve roots with neurogenic bowel (fecal incontinence) or bladder (urinary retention or incontinence) dysfunction. - Has been previously diagnosed with clinically significant peripheral neuropathy. - Has significant vascular disease causing vascular claudication. - Has a medical contraindication that prevents the patient from receiving spinal injections (i.e., allergy to contrast media used to aid in placement of the needle in the epidural space). - Has anterolisthesis with more than 2mm of translation at the involved level. - Has evidence of prior fracture or trauma to the L1, L2, L3, L4, or L5 levels in either compression or burst. - Has lumbar scoliosis with a Cobb angle of greater than 15°. - Has lumbar kyphosis or flat back syndrome. - Has sustained a hip fracture within the last year. - Has any of the following (if “Yes” to any of the below risk factors, a lumbar spine DEXA Scan will be required to determine eligibility): - Previous diagnosis of osteoporosis, osteopenia, or osteomalacia. - Postmenopausal non-black female over 60 years of age who weighs less than 140 pounds. - Postmenopausal female who has sustained a non-traumatic hip, spine, or wrist fracture. - Male over the age of 60 who has sustained a non-traumatic hip or spine fracture. - If the level of DEXA T-score is -1.0 or lower (i.e., -1.5, -2.0, etc.), the patient is excluded from the study. - Has obesity defined by BMI greater than or equal to 40. - Has a documented allergy to silicone, polyethylene, titanium or latex. - Has overt or active bacterial infection, either local or systemic, and/or potential for bacteremia. - Has a suppressed immune system or has taken steroids daily for more than one month within the last year (excluding low dose inhalers for the treatment of asthma). - Has a history of autoimmune disease. - Has presence of active malignancy or prior history of malignancy within the last 5 years (except for basal cell carcinoma of the skin). - Has presence or prior history of a spinal malignancy. - Has chronic or acute renal and/or hepatic failure or prior history of renal and/or hepatic parenchymal disease. - Has any disease (e.g., neuromuscular disease) that would preclude accurate clinical evaluation of the safety and effectiveness of the treatment regimens in this study. PMA P240043: FDA Summary of Safety and Effectiveness Data Page 17 of 65 {17} - Has received treatment with an investigational therapy (device and/or pharmaceutical) within 30 days prior to entering the study or such treatment is planned during the 24 months following enrollment in the study. - Has an implantable metal device (e.g., stimulator, pacemaker) and is unable to have an MRI. - Is an alcohol and/or drug abuser, as defined by currently undergoing treatment for alcohol and/or drug abuse. - Is mentally incompetent. If questionable, obtain psychiatric consult. - Has a Waddell Signs of Inorganic Behavior score of 3 or greater. - Is a prisoner. ## 2. Follow-up Schedule All subjects were scheduled to return for follow-up examination at 6 weeks, 3 months, 6 months, 12 months, 24 months post-operatively. Pre-operatively, subjects were confirmed to meet the enrollment criteria, to have given Informed Consent, along with other pretreatment evaluations. Post-operatively, the objective parameters measured during the study included ODI, back and leg pain assessment, neurological assessment, and radiological evaluation. AEs and complications were recorded at all visits. Table 5 includes detailed information regarding the schedule of study assessments and data collected at each timepoint. The key timepoints are shown below in the tables summarizing safety and effectiveness. Crossover subjects were assessed at the same follow-up timepoints, after being implanted with the DIAM™ Spinal Stabilization System, as investigational and control subjects originally enrolled in the study. Therefore, all presentations of safety and effectiveness results for crossover subjects below represent data collected from the point the subject received the crossover treatment. For example, 6-month crossover data represent results 6 months after subjects received the crossover treatment and not 6 months after crossover subjects were originally enrolled in the control arm of the study. Table 5: Schedule of Study Assessments | Procedure | Study Time Period | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Pre-Operative/On Treatment | Surgery / Hospital / Discharge* | 6Wks ± 2Wks | 3M ± 2Wks | 6M ± 1M | 12M ± 2M | 24M ± 2M & Annually Until Required Follow-Up Complete | Additional Evaluation*** | | Pre-Treatment Information | | | | | | | | | | Confirm subject eligibility | X | | | | | | | | PMA P240043: FDA Summary of Safety and Effectiveness Data Page 18 of 65 {18} | Procedure | Study Time Period | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Pre-Operative/On Treatment | Surgery / Hospital / Discharge# | 6Wks ± 2Wks | 3M ± 2Wks | 6M ± 1M | 12M ± 2M | 24M ± 2M & Annually Until Required Follow-Up Complete | Additional Evaluation*** | | Obtain informed consent | X | | | | | | | | | Case Report Forms | | | | | | | | | | Medical history | X | | | | | | | | | Pre-treatment concomitant medications | X | | | | | | | | | Neurological status | X | X | X | X | X | X | X | X | | Surgery data# and hospital discharge | | X | | | | | | | | Non-operative treatment data (control only) | X | | X | X | X | X | X | | | Patient data | X | | X | X | X | X | X | X | | Additional medications / injections (if applicable) | | | X | X | X | X | X | X | | Patient survey | X | | X | X | X | X | X | X | | ODI | X | | X | X | X | X | X | X | | Back & leg pain (NRS) | X | | X | X | X | X | X | X | | SF-36 | X | | X | X | X | X | X | X | | Adverse event assessment (as needed) | | X | X | X | X | X | X | X | | Study deviation-patient or site (if applicable) | X | X | X | X | X | X | X | | | Patient disposition** | X | X | X | X | X | X | X | | | Radiologic Procedures | | | | | | | | | | Anterior/posterior | X | X | X | X | X | X | X | | | Lateral | X | X | X | X | X | X | X | | | Lateral Flexion/extension | X | | X | X | X | X | X | | | MRI | X | | | | | X | X* | | | Lumbar spine DEXA scan* | X | | | | | | | | * Only collected through 24 months ** Filled out only once at time of subject completion or withdrawal *** Additional Evaluation CRF's were required for subjects who were scheduled for surgery based on the unsatisfactory outcome of their original Treatment if the subject had not had an evaluation within the last 2 months prior to surgery. PMA P240043: FDA Summary of Safety and Effectiveness Data Page 19 of 65 {19} # applies to investigational subjects and crossover subjects + as required by exclusion criteria #22. # 3. Clinical Endpoints With regards to safety, the DIAM™ Spinal Stabilization System was assessed by comparison to the non-operative care control group with respect to the nature and frequency of adverse events (overall and in terms of severity and relationship to the implant), subsequent index level surgical procedures, and maintenance or improvement in neurological status. Given the ability of control subjects to cross over to the investigational group, all data available for subjects treated with the investigational device were also assessed. With regards to effectiveness, the DIAM™ Spinal Stabilization System was assessed by comparison to the non-operative care control group with respect to a primary composite endpoint, as described below. Effectiveness was further assessed by assessing improvement in ODI, absence of Serious AEs (SAEs) that were treatment associated, and absence of subsequent surgical procedures at the index level. # Primary Endpoint The primary composite endpoint was defined as follows: - Pain/disability success measured as greater than or equal to 15-point improvement in ODI score relative to baseline - No SAE classified as "implant associated," "implant-/surgical procedure associated," or non-operative treatment associated, and - No additional surgical procedure at the involved level classified as a failure. Subject success was evaluated using the primary composite endpoint above at 24 months post-operatively (Month 24). # Secondary Endpoints Additional secondary endpoints were evaluated to further define the safety and effectiveness of the DIAM™ Spinal Stabilization System. Secondary effectiveness variables include, but were not limited to: - ODI - Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) - NRS Back Pain Intensity - Radiographic Evaluations - Disc Height - Intervertebral Angle and Angular Motion - Implant Location PMA P240043: FDA Summary of Safety and Effectiveness Data {20} $\mathrm{O}$ Integrity of Spinous Process - Subject Satisfaction with Study Treatment - Subject Global Perceived Effect - Work Status ## B. Accountability of PMA Cohort At the time of database lock, 311 subjects were enrolled in the PMA study, with n=207 randomized to the investigational group, and n=104 randomized to the non-operative control group (Intent-to-Treat (ITT) population). 90.7% (253/279) of subjects were available for analysis at Month 24. A total of 59 subjects randomized to the non-operative control group met the pre-defined conditions and elected to crossover and receive the investigational device. This subset of subjects was then followed for at least 24 months post-operatively, using the same follow-up timepoints as the originally enrolled subjects, and assessed for primary overall success separately from the investigational cohort. At Month 24, 98.3% (58/59) of the crossover subjects were available for analysis of the Composite Clinical Success (CCS). A summary of the subject accounting and follow-up compliance (Table 6) and subject accounting tree (Figure 2) are presented below, followed by a description of the analysis populations. PMA P240043: FDA Summary of Safety and Effectiveness Data Page 21 of 65 {21} Table 6: Subject Accounting and Follow-up Compliance for Investigational, Control, and Crossover mITT-Followed | | Month 12 | | | Month 24 | | | | --- | --- | --- | --- | --- | --- | --- | | | I | C | Crossover | I | C | Crossover | | Accounting | | | | | | | | (1) Theoretical follow-up* | 182 | 97 | 59 | 182 | 97 | 59 | | (2) Cumulative Death | 0 | 0 | 0 | 0 | 1 | 0 | | (3a) Crossover | 0 | 48 | 0 | 0 | 55 | 0 | | (3b) Cumulative Non-Crossover SSI Failures | 6 | 7 | 1 | 12 | 9 | 3 | | (4) Not Yet Overdue | 0 | 0 | 0 | 0 | 0 | 0 | | (5) Deaths + SSI Failures + Crossover among Theoretically Due | 6 | 55 | 1 | 12 | 65 | 3 | | (6) Expected Due [(6)=(1)-(4)-(5)]A | 176 | 42 | 58 | 170 | 32 | 56 | | (7) SSI Failures + Crossover among Theoretically Due | 6 | 55 | 1 | 12 | 64 | 3 | | (8) Expected Due + SSI Failures + Crossover among Theoretically Due [(8)=(6)+(7)] | 182 | 97 | 59 | 182 | 96 | 59 | | All Evaluated Accounting (ActualB) | | | | | | | | (9) Procedures with any clinical data in intervalC | 170 | 33 | 55 | 156 | 20 | 54 | | (10) Visit Compliance (%)D | 97% | 79% | 95% | 92% | 63% | 96% | | (11) ODI Evaluation (censored for SSI) | 170 | 33 | 55 | 156 | 20 | 54 | | (12) Back Pain Evaluation (censored for SSI) | 169 | 33 | 55 | 155 | 20 | 53 | | (13) Leg Pain Evaluation (censored for SSI) | 170 | 33 | 55 | 156 | 19 | 53 | | (14) Neurological Evaluation (not censored for SSI) | 174 | 39 | 56 | 166 | 26 | 57 | | (15) Composite Clinical Success (CCS) | 176 | 88 | 57 | 169 | 84 | 58 | | (16) ActualB % Follow-up for CCSE | 97% | 91% | 97% | 93% | 88% | 98% | | Within Window Accounting (ActualF) | | | | | | | | (17) Procedures with any clinical data in intervalC | 163 | 27 | 53 | 146 | 18 | 50 | | (18) Visit Compliance (%)D | 93% | 64% | 91% | 86% | 56% | 89% | | (19) ODI Evaluation (censored for SSI) | 163 | 27 | 53 | 146 | 18 | 50 | | (20) Back Pain Evaluation (censored for SSI) | 162 | 27 | 53 | 145 | 18 | 49 | | (21) Leg Pain Evaluation (censored for SSI) | 163 | 27 | 53 | 146 | 17 | 49 | | (22) Neurological Evaluation (not censored for SSI) | 167 | 33 | 54 | 156 | 24 | 53 | | (23) Composite Clinical Success (CCS) | 169 | 83 | 55 | 160 | 82 | 54 | | (24) ActualF % Follow-up for CCSE | 93% | 86% | 93% | 88% | 85% | 92% | | * Note, 56 control subjects crossed over prior to Month 24 (n=1 had a treatment surgery first, and is captured in row (3b)). Three (3) additional subjects crossed over after Month 24 (Day 790); therefore, all 59 crossover subjects are included above. A Includes subjects with no SSI prior to the visit specified. B Patients with any follow-up data reviewed or evaluated by investigator ("all evaluated" accounting). C Defined as ODI, back pain, or leg pain data after censoring for SSI. D Denominator is row (6). E Denominator is row (8). F Patients with complete data for each endpoint, within window. | | | | | | | (1) Theoretical follow-up: The theoretical follow-up is the number of subjects that would be theoretically due for Month 12 and Month 24 follow-up before database closure. All subjects in the mITT-Followed population were theoretically due. (2) Cumulative deaths: Cumulative deaths up to the date of the exact anniversary defining the current interval. (3a) Crossover: Subjects who had crossover surgery prior to specified visit and the end of visit window. (3b) Cumulative Non-Crossover SSI Failures: Subjects who had any non-crossover SSI prior to specified visit and the end of visit window. This includes revisions, removals, re-operations, supplemental fixations, and treatment surgeries. (4) Not Yet Overdue: Includes subjects whose clinical data has not been collected, but they are in between surgical/treatment anniversary and protocol specified follow-up window. Such subjects may not yet be observed, and follow-up compliance estimates account for this by removing such subjects from the denominator when determining compliance ratios. There are no subjects Not Yet Overdue at the time of this database lock. (5) Deaths + SSI Failures + Crossover among Theoretically Due: This row records the sum of deaths and all SSI failures, including crossovers. The SSIs, including crossovers, must have occurred prior to the specified visit and before the end of the visit window to be counted in this row. This row is subtracted from theoretically due to determine the number expected due for clinical evaluation. PMA P240043: FDA Summary of Safety and Effectiveness Data {22} (6) Expected Due: This row is the number of subjects expected for a given time interval. This includes the theoretical number of subjects due to be evaluated minus the number who died, were SSI/Crossover failures, or were not yet overdue. Expected = Theoretical – [Death + Failures + Not yet overdue]. This row serves as the denominator for Visit Compliance and includes subjects lost to follow-up. (7) SSI Failures + Crossover among Theoretically Due: SSI Failures, including crossovers, that need to be “added back” to the number of expected due to serve as the denominator for CCS counts when determining CCS follow-up compliance. (8) Expected Due + SSI Failures + Crossover among Theoretically Due: Expected due plus theoretical due failures is computed by adding rows (6) and (7). This row serves as the denominator for CCS outcomes because CCS status is known for subjects with an SSI. (9) and (17) Procedures with any clinical data in interval: These rows indicate the number of subjects with any ODI, back pain, or leg pain data after SSI censoring for all evaluated subjects (9) and for all subjects that are within window (17) among expected due subjects. (10) and (18) Visit Compliance (%): These rows indicate the percentage of subjects compliant with the specified visit scheduled. (10) is the percentage of all evaluated among expected due subjects [(9) out of (6)], and (18) is the percentage of subjects within window among expected due subjects [(17) out of (6)]. (11) and (19) ODI Evaluation (censored for SSI): These rows indicate the number of subjects with any ODI data after SSI censoring for all evaluated subjects (11) and for all subjects that are within window (19) among expected due subjects. (12) and (20) Back Pain Evaluation (censored for SSI): These rows indicate the number of subjects with any back pain data after SSI censoring for all evaluated subjects (12) and for all subjects that are within window (20) among expected due subjects. (13) and (21) Leg Pain Evaluation (censored for SSI): These rows indicate the number of subjects with any leg pain data after SSI censoring for all evaluated subjects (13) and for all subjects that are within window (21) among expected due subjects. (14) and (22) Neurological Evaluation (not censored for SSI): These rows indicate the number of subjects with any neurological evaluations for all evaluated subjects (14) and for all subjects that are within window (22) among expected due subjects. (15) and (23) Composite Clinical Success (CCS): These rows indicate the number of subjects evaluable for CCS at specified visit for all evaluated subjects (15) and for all subjects that are within window (23). Subjects are evaluable for CCS if they had any SSI or treatment-associated AE before the end of the visit window or if they had an ODI evaluation at the specified visit. (16) and (24) Actual % Follow-up for CCS: These rows indicate the percentage of subjects evaluable for CCS at specified visit for all evaluated subjects (16) and for all subjects that are within window (24). Subjects are evaluable for CCS if they had any SSI or treatment-associated AE before the end of the visit window or if they had an ODI evaluation at the specified visit. The denominator for percentages is expected due plus SSI failures, including crossovers (8). PMA P240043: FDA Summary of Safety and Effectiveness Data Page 23 of 65 {23} The subject accounting tree for the DIAM™ IDE study is depicted below in Figure 2. ![img-1.jpeg](img-1.jpeg) Figure 2: Subject Accounting Tree PMA P240043: FDA Summary of Safety and Effectiveness Data {24} # Analysis Populations For the purpose of assessing safety and effectiveness, the following analysis populations were used: - ITT Analysis Set – 311 Subjects: The ITT analysis set included all subjects randomized to either the DIAM™ Spinal Stabilization System or non-operative care. This included 207 subjects randomized to DIAM™ Spinal Stabilization System and 104 subjects randomized to non-operative care. - Modified Intent-to-Treat (mITT) Analysis Set – 283 Subjects: The mITT analysis set includes all subjects in the ITT analysis set for which treatment was attempted. This includes 182 DIAM™ Spinal Stabilization System subjects and 101 non-operative care subjects. The DIAM™ Spinal Stabilization System mITT analysis set includes one subject in which treatment was initiated and but not completed due to an intraoperative adverse event. This subject was defined as a composite endpoint failure. The non-operative care mITT analysis set includes 4 subjects that initiated non-operative care but for whom there was no follow-up. - Modified Intent-to-Treat Followed (mITT-Followed) Analysis Set – 279 Subjects: The mITT-Followed analysis set includes all subjects in the mITT analysis set with any follow-up. Therefore, this is the mITT analysis set excluding the 4 controls that completed treatment but who had no post treatment follow-up. The sample sizes are 182 DIAM™ Spinal Stabilization System subjects and 97 non-operative care controls. Safety data are presented for the mITT-Followed analysis set. - Back Pain Predominate Modified Intent-to-Treat (BPPmITT) Analysis Set – 220 Subjects: The BPPmITT analysis set is a subset of the mITT-Followed dataset which excludes subjects with leg pain intensity scores ≥ back pain intensity scores at baseline. This analysis set comprises 144 DIAM™ Spinal Stabilization System subjects and 76 non-operative care controls. The BPPmITT analysis set was designated the primary endpoint analysis population. Effectiveness data are presented for the BPPmITT analysis set due to the retrospective modification to the Indications for Use Statement for the DIAM™ Spinal Stabilization System. - Crossover Analysis Set – 59 Subjects: This analysis set includes all subjects who were randomized to the control group and elected to receive the DIAM™ Spine Stabilization System as a treatment surgery. A total of 59 control subjects ultimately crossed over to receive the DIAM™ Spinal Stabilization System treatment: 56 within 24-months and 3 additional after the 24-month visit. For crossover subjects, outcome measurements PMA P240043: FDA Summary of Safety and Effectiveness Data Page 25 of 65 {25} after implanting the investigational device were summarized as crossover cohort and compared to measurements obtained immediately prior to surgery. Effectiveness data are also presented for a subset of crossover subjects (Crossover BPP), including 49 crossover subjects with back pain intensity scores $>$ leg pain intensity scores. # C. Study Population Demographics and Baseline Parameters Demographics and baseline parameters are provided for the mITT analysis set (182 investigational; 101 non-operative care) (all randomized subjects in whom study treatment was attempted) and all 59 subjects included in the crossover sub-group. All available demographics and baseline data are presented. As shown below, overall, the treatment groups had similar mean age, height, weight, and BMI, gender distribution, race distribution, education level distribution, proportion of subjects with ongoing spinal litigation, history of prior back surgery, and smoking history. In addition to the similarities in demographics, the investigational and non-operative care control groups had similar baseline scores, including mean ODI scores, NRS back pain, SF-36 mental scores and SF-36 physical scores. In summary, randomization was effective in providing a well-balanced study population, with similar demographic, baseline, and clinical characteristics between the investigational and non-operative care control groups. The baseline and demographics for the mITT analysis population are summarized in Table 7, Table 8, Table 9, and Table 10 for continuous variables, categorical variables, clinical endpoints, and neurological status, respectively. The data demonstrate the two treatment groups have no major difference in terms of characteristics of enrolled subjects. The demographics of the study population are typical for a spine study performed in the US. Table 7: Summary of Baseline and Demographic Continuous Variables – Investigational, Control, and Crossover mITT | | Investigational | | | | | | Control | | | | | | Crossover | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | N | Mean | SD | Med | Min | Max | N | Mean | SD | Med | Min | Max | N | Mean | SD | Med | Min | Max | | Age (years) | 182 | 42.5 | 11.0 | 43.5 | 18.0 | 69.0 | 101 | 44.6 | 10.4 | 44.0 | 23.0 | 70.0 | 59 | 45.8 | 10.2 | 45.0 | 23.0 | 70.0 | | Height (in) | 182 | 67.5 | 3.6 | 67.0 | 59.0 | 78.0 | 101 | 67.8 | 4.3 | 68.0 | 60.0 | 77.0 | 59 | 67.9 | 4.4 | 68.0 | 60.0 | 77.0 | | Weight (lbs) | 182 | 183.7 | 39.6 | 181.0 | 108.0 | 320.0 | 101 | 188.2 | 44.5 | 185.0 | 108.0 | 318.0 | 59 | 186.9 | 47.8 | 185.0 | 108.0 | 311.0 | | BMI (kg/m2) | 182 | 28.3 | 5.2 | 27.4 | 18.5 | 41.1 | 101 | 28.6 | 5.6 | 27.8 | 17.4 | 39.7 | 59 | 28.3 | 5.9 | 27.3 | 17.4 | 39.3 | PMA P240043: FDA Summary of Safety and Effectiveness Data {26} Table 8: Summary of Baseline and Demographic Categorical Variables – Investigational, Control, and Crossover mITT | | Investigational | | | Control | | | Crossover | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | N | n | % | N | n | % | N | n | % | | Sex | | | | | | | | | | | Female | 182 | 105 | 57.7% | 101 | 50 | 49.5% | 59 | 29 | 49.2% | | Male | 182 | 77 | 42.3% | 101 | 51 | 50.5% | 59 | 30 | 50.8% | | Race | | | | | | | | | | | Caucasian | 182 | 167 | 91.8% | 101 | 92 | 91.1% | 59 | 55 | 93.2% | | Black | 182 | 3 | 1.6% | 101 | 5 | 5.0% | 59 | 1 | 1.7% | | Asian | 182 | 1 | 0.5% | 101 | 0 | 0.0% | 59 | 0 | 0.0% | | Hispanic | 182 | 11 | 6.0% | 101 | 1 | 1.0% | 59 | 1 | 1.7% | | Other | 182 | 0 | 0.0% | 101 | 3 | 3.0% | 59 | 2 | 3.4% | | Education Level | | | | | | | | | | | < High School | 182 | 13 | 7.1% | 101 | 7 | 6.9% | 59 | 3 | 5.1% | | High School | 182 | 50 | 27.5% | 101 | 22 | 21.8% | 59 | 11 | 18.6% | | > High School | 182 | 117 | 64.3% | 101 | 72 | 71.3% | 59 | 45 | 76.3% | | Not Reported | 182 | 2 | 1.1% | 101 | 0 | 0.0% | 59 | 0 | 0.0% | | Spinal Litigation | | | | | | | | | | | Yes | 182 | 25 | 13.7% | 101 | 11 | 10.9% | 59 | 7 | 11.9% | | No | 182 | 157 | 86.3% | 101 | 90 | 89.1% | 59 | 52 | 88.1% | | Back Surgery Hx | | | | | | | | | | | Yes | 182 | 1 | 0.5% | 101 | 4 | 4.0% | 59 | 2 | 3.4% | | No | 182 | 181 | 99.5% | 101 | 97 | 96.0% | 59 | 57 | 96.6% | | Tobacco | | | | | | | | | | | Yes | 182 | 46 | 25.3% | 101 | 34 | 33.7% | 59 | 18 | 30.5% | | No | 182 | 134 | 73.6% | 101 | 65 | 64.4% | 59 | 40 | 67.8% | | Not Reported | 182 | 0 | 0.0% | 101 | 0 | 0.0% | 59 | 1 | 1.7% | Table 9: Comparison of Baseline Clinical Endpoints – Investigational, Control, and Crossover mITT | | Investigational | | | | | | Control | | | | | | Crossover | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | N | Mean | SD | Med | Min | Max | N | Mean | SD | Med | Min | Max | N | Mean | SD | Med | Min | Max | | Back Pain* | 182 | 16.8 | 2.3 | 17.0 | 9.0 | 20.0 | 101 | 16.2 | 2.8 | 17.0 | 8.0 | 20.0 | 59 | 16.4 | 2.7 | 17.0 | 8.0 | 20.0 | | Leg Pain* | 182 | 10.3 | 6.2 | 12.0 | 0.0 | 20.0 | 101 | 9.1 | 6.5 | 10.0 | 0.0 | 20.0 | 59 | 10.3 | 6.9 | 12.0 | 0.0 | 20.0 | | ODI | 182 | 50.4 | 13.9 | 48.0 | 30.0 | 94.0 | 101 | 50.4 | 13.2 | 50.0 | 30.0 | 82.0 | 59 | 55.4 | 13.1 | 54.0 | 32.0 | 96.0 | | SF36: MCS | 181 | 36.0 | 9.0 | 36.6 | 13.4 | 54.0 | 101 | 35.9 | 9.7 | 37.0 | 11.0 | 56.0 | 59 | 35.2 | 10.1 | 35.8 | 16.3 | 51.9 | | SF36: PCS | 181 | 31.5 | 6.3 | 30.5 | 16.4 | 47.8 | 101 | 30.5 | 5.7 | 29.8 | 19.8 | 46.5 | 59 | 29.7 | 5.3 | 28.5 | 21.7 | 43.1 | | *Baseline Back Pain and Leg Pain Scores were each evaluated on a 0-20 scale comprising pain intensity (0-10) and pain frequency (0-10) components. | | | | | | | | | | | | | | | | | | | Table 10: Summary of Baseline Neurological Status – Investigational, Control, and Crossover mITT | | Investigational | | | Control | | | Crossover | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | N | n | % | N | n | % | N | n | % | | Normal Motor Function | 182 | 182 | 100.0% | 101 | 101 | 100.0% | 59 | 58 | 98.3% | | Normal Sensory Function | 182 | 164 | 90.1% | 101 | 95 | 94.1% | 59 | 56 | 94.9% | | Normal Reflexes | 182 | 164 | 90.1% | 101 | 92 | 91.1% | 59 | 54 | 91.5% | | Normal Straight Leg Raise | 182 | 151 | 83.0% | 101 | 79 | 78.2% | 59 | 49 | 83.1% | PMA P240043: FDA Summary of Safety and Effectiveness Data Page 27 of 65 {27} Data was collected on the type of non-operative care received by control subjects in the mITT population. Treatments received by control subjects at the initial treatment included: education (99% - 100/101); medication (82.2% - 83/101); physical therapy (68.3% - 69/101); and spinal injection (36.6% - 37/101). The continuous operative variables are summarized in Table 11 for subjects randomized to the investigational group and subjects who were randomized to the non-operative care control group and subsequently elected to crossover. The average operative times were 62.6 minutes and 59.5 minutes with mean blood loss of 31.4 mL and 35.6 mL in the investigational and crossover groups, respectively. Most subjects were discharged from the hospital in less than a day with a mean length of stay of 0.8 days reported in both the investigational and crossover cohorts. General anesthesia was utilized for all investigational and crossover subjects with a reported anesthesia type. In both the investigational and crossover cohorts, the majority of subjects were treated at L4-L5. In the investigational cohort, 4.9% (9/182) subjects were treated at L2-L3, 7.1% (13/182) were treated at L3-L4, and 87.9% (160/182) were treated at L4-L5. The distribution of levels treated was similar in the crossover subjects: 3.4% (2/59) at L2-L3, 5.1% (3/59) at L3-L4, 89.8% (53/59) at L4-L5, and 1.7% (1/59) at L5-L6 (anatomic variant). Regarding surgery site, 62.1% (113/182) and 59.3% (35/59) of subjects were treated in outpatient procedures, and 37.9% (69/182) and 40.7% (24/59) were inpatient procedures in the investigational and crossover groups, respectively. Table 11: Summary of Operative Details – Continuous Variables Investigational mITT-Followed and Crossover | | Investigational | | | | | | Crossover | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | N | Mean | SD | Med | Min | Max | N | Mean | SD | Med | Min | Max | | Surgery Time (min) | 182 | 62.6 | 18.7 | 60.0 | 21.0 | 123.0 | 59 | 59.5 | 20.3 | 56.0 | 25.0 | 138.0 | | Blood Loss (mL) | 182 | 31.4 | 26.9 | 25.0 | 0.0 | 100.0 | 59 | 35.6 | 29.9 | 23.0 | 9.0 | 100.0 | | Length of Stay (days) | 182 | 0.8 | 0.7 | 1.0 | 0.0 | 3.0 | 59 | 0.8 | 0.9 | 1.0 | 0.0 | 6.0 | ## D. Safety and Effectiveness Results ### 1. Safety Results The analysis of safety was based on the mITT-Followed Analysis population of 279 subjects available beyond the Month 24 evaluation (day 790). Note that the listings of days related to adverse event results (e.g., "day 790") represents the upper bound of the follow-up window (e.g., 24 months + 2 months). The key safety outcomes for this study are presented below in Table 12 to Table 24. ### Adverse Event Summary The safety endpoint evaluated the rate of AEs, categorized by severity (mild, moderate or severe), relationship to the implant, surgical procedure, or non-operative care, and SAEs. AEs were reviewed by an independent Clinical Events Committee (CEC) and adjudicated for severity and relationship to the non-operative care, implant, and/or surgical procedure in accordance with the definitions provided below. PMA P240043: FDA Summary of Safety and Effectiveness Data {28} PMA P240043: FDA Summary of Safety and Effectiveness Data Page 29 of 65 # Severity AEs were assessed for severity using the following definitions: - Mild (Grade 1) – Noticeable to the subject but did not interfere with routine activity, and for subjects in the investigational group, the AE did not require removal of the implant; - Moderate (Grade 2) – Interfered with routine activity but responded to symptomatic therapy or rest, and for subjects in the investigational group, the AE did not require removal of the implant; - Severe (Grade 3) – Significantly limited the subject’s ability to perform routine activities despite symptomatic therapy, and for subjects in the investigational group, the AE may require removal of the implant; and, - Life-threatening (Grade 4) – The subject is at immediate risk of death, and for subjects in the investigational group, the AE may require removal of the implant. # Serious Adverse Events An SAE was defined as an AE that: led to a death; led to fetal distress, fetal death, or a congenital abnormality or birth defect; or, led to a serious deterioration in health of the subject that: - Resulted in a life-threatening illness or injury; - Resulted in permanent impairment of a body structure or function; - Required in-patient hospitalization or prolongation of existing hospitalization; or - Resulted in medical or surgical intervention to prevent permanent impairment to body structure or a body function. # Association with Study Treatment For investigational and crossover subjects (i.e., subjects randomized to non-operative care who elected to undergo implantation with the DIAM™ Spinal Stabilization System), association of an AE with the investigational treatment was assessed according to the following definitions: - Implant-Associated AE: An AE for which there was a reasonable possibility that the event may have been caused primarily by the implant/implant component. - Surgical Procedure-Associated AE: An AE for which there was a reasonable possibility that the event may have been caused primarily by the surgical procedure. - Implant/Surgical Procedure-Associated AE: An AE for which there was a reasonable possibility that the event may have been caused primarily by the implant/implant component and/or the surgical procedure but cannot be definitively associated exclusively with the implant or exclusively with the surgical procedure. - Undetermined AE: An AE for which sufficient information to determine the causality of the event was not available. - Not Related AE: An AE for which sufficient information existed to indicate that the etiology of the event was unrelated to the study treatment. {29} For non-operative care control subjects, association of an AE with non-operative care treatments was assessed according to the following definitions: - Non-operative Treatment Associated AE: An AE for which there was a reasonable possibility that the event may have been caused primarily by the non-operative treatment. - Undetermined AE: An AE for which sufficient information was not available to determine its causality. - Not Related AE: An AE for which sufficient information existed to indicate that the etiology of the event was unrelated to the study treatment. For any event categorized by CEC as implant-associated, surgical procedure-associated, implant/surgical procedure-associated, or non-operative care associated, the CEC assigned the following relationship categories. - Definitely Associated: An AE that has a strong causal relationship. An AE that follows a strong temporal relationship, follows a known response pattern, and cannot reasonably be explained by known characteristics of the subject’s clinical state or other therapies. - Probably Associated: An AE that potentially has a causal relationship. The AE has a reasonable temporal relationship and alternative etiology is less likely compared to the potential relationship to the use of the investigational device/procedure or non-operative treatment (control only). - Possibly Associated: An AE that potentially has a causal relationship. The AE has a reasonable temporal relationship to the use of the investigational device/procedure, but alternative etiology is equally likely compared to the potential relationship to the use of the investigational device/procedure or non-operative treatment (control only). Please note, the Month 24 and Month 60 safety tables below present all AEs that occurred within that interval following initial randomized treatment to the investigational or control arms, regardless of whether the subject received additional treatment. Accordingly, AEs presented for the control group include AEs that occurred after crossover treatment. However, AEs presented for the crossover group do not include AEs that occurred prior to subjects receiving the crossover treatment. The tables displaying treatment-associated events provide context on whether events that occurred over the 24-month (day 790) or 60-month (day 1,885) intervals were associated to the implant and/or surgical procedure. Further, a separate set of select safety tables that list AEs through six months (day 210) are provided since the comparison between the investigational and non-operative care control treatments through 6 months is not impacted by AEs occurring after crossover in the control group at later timepoints. AEs through Month 6 for the investigational, crossover, and control groups are reported in Table 12. The results indicate that through Month 6, 76.9% (140/182) of investigational subjects, 66.0% (64/97) of control subjects, and 76.3% (45/59) of crossover subjects PMA P240043: FDA Summary of Safety and Effectiveness Data Page 30 of 65 {30} experienced at least one AE. The percentage of subjects who reported at least one SAE was 13.7% (25/182) in the investigational group, 22.7% (22/97) in the control group, and 15.3% (9/59) in the crossover group. While more subjects in the investigational and crossover groups experienced an AE, this is not unexpected for an implant relative to non-operative care. Table 12: Comparison of Summary of Safety Events up to 6 Months – Investigational and Control mITT-Followed and Crossover | | Investigational (N=182) | | | Control (N=97) | | | Crossover (N=59) | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Events | n | % | Events | n | % | Events | n | % | | Any adverse event | 319 | 140 | 76.9% | 117 | 64 | 66.0% | 92 | 45 | 76.3% | | Any implant/surgical procedure associated AE | 6 | 6 | 3.3% | 0 | 0 | 0.0% | 2 | 2 | 3.4% | | Any implant only associated AE | 1 | 1 | 0.5% | 0 | 0 | 0.0% | 1 | 1 | 1.7% | | Any surgical procedure only associated AE | 46 | 44 | 24.2% | 0 | 0 | 0.0% | 25 | 22 | 37.3% | | Any nonoperative treatment associated AE | 0 | 0 | 0.0% | 1 | 1 | 1.0% | 0 | 0 | 0.0% | | Any serious AE | 27 | 25 | 13.7% | 23 | 22 | 22.7% | 9 | 9 | 15.3% | | Any implant/surgical procedure associated SAE | 3 | 3 | 1.6% | 0 | 0 | 0.0% | 0 | 0 | 0.0% | | Any implant only associated SAE | 0 | 0 | 0.0% | 0 | 0 | 0.0% | 0 | 0 | 0.0% | | Any surgical procedure only associated SAE | 10 | 10 | 5.5% | 0 | 0 | 0.0% | 6 | 6 | 10.2% | | Any nonoperative treatment associated SAE | 0 | 0 | 0.0% | 1 | 1 | 1.0% | 0 | 0 | 0.0% | | Spinous Process Fracture | 13 | 13 | 7.1% | 0 | 0 | 0.0% | 5 | 5 | 8.5% | | Deaths | 0 | 0 | 0.0% | 0 | 0 | 0.0% | 0 | 0 | 0.0% | | Only adverse events through the first 210 days are included. | | | | | | | | | | AEs through Month 24 for the investigational, crossover, and control groups are reported in Table 13. The results indicate that through Month 24, 92.9% (169/182) of investigational subjects, 89.7% (87/97) of control subjects, and 91.5% (54/59) of crossover subjects experienced at least one AE. It should be noted that some AEs captured under the control group through Month 24 may be related to subjects that crossed over. Nevertheless, the investigational and crossover subjects experienced an AE rate within only a few percent higher than the control group, and this again is to be expected with an implant relative to non-operative care. PMA P240043: FDA Summary of Safety and Effectiveness Data Page 31 of 65 {31} Table 13: Comparison of Summary of Safety Events up to 24 Months – Investigational and Control mITT-Followed and Crossover | | Investigational (N=182) | | | Control (N=97) | | | Crossover (N=59) | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Events | n | % | Events | n | % | Events | n | % | | Any adverse event | 638 | 169 | 92.9% | 314 | 87 | 89.7% | 173 | 54 | 91.5% | | Any implant/surgical procedure associated AE | 6 | 6 | 3.3% | 0 | 0 | 0.0% | 2 | 2 | 3.4% | | Any implant only associated AE | 4 | 4 | 2.2% | 0 | 0 | 0.0% | 1 | 1 | 1.7% | | Any surgical procedure only associated AE | 46 | 44 | 24.2% | 0 | 0 | 0.0% | 27 | 24 | 40.7% | | Any nonoperative treatment associated AE | 0 | 0 | 0.0% | 2 | 2 | 2.1% | 0 | 0 | 0.0% | | Any serious AE | 69 | 59 | 32.4% | 47 | 42 | 43.3% | 19 | 16 | 27.1% | | Any implant/surgical procedure associated SAE | 3 | 3 | 1.6% | 0 | 0 | 0.0% | 1 | 1 | 1.7% | | Any implant only associated SAE | 2 | 2 | 1.1% | 0 | 0 | 0.0% | 0 | 0 | 0.0% | | Any surgical procedure only associated SAE | 10 | 10 | 5.5% | 0 | 0 | 0.0% | 6 | 6 | 10.2% | | Any nonoperative treatment associated SAE | 0 | 0 | 0.0% | 2 | 2 | 2.1% | 0 | 0 | 0.0% | | Spinous Process Fracture | 14 | 14 | 7.7% | 0 | 0 | 0.0% | 6 | 6 | 10.2% | | SSI | 13 | 12 | 6.6% | 68 | 65 | 67.0% | 4 | 3 | 5.1% | | Deaths | 1* | 1 | 0.5% | 1** | 1 | 1.0% | 0 | 0 | 0.0% | | Only adverse events through the first 790 days are included. *Cause of death was acidosis and septic shock at approximately 24 months post-operatively. **Cause of death was hypertensive cardiomegaly at 23 months post-treatment. | | | | | | | | | | The mITT-Followed population (investigational and non-operative care) and the crossover population also reported comparable rates of AEs through the 60-month follow-up, as shown below. The overall adverse event rate was 96.2% (175/182) in the investigational group, 93.8% (91/97) in the control group, and 94.9% (56/59) in the crossover group. Similar proportions of subjects in the investigational, control, and crossover treatment groups experienced any SAE during the 60-month follow-up. The percentage of subjects who reported at least one SAE was 42.3% (77/182) in the investigational group, 52.6% (51/97) in the control group, and 40.7% (24/59) in the crossover group. Compared to Month 24, there were no significant differences in the rates of implant-associated, surgical procedure-associated, or implant/surgical procedure-associated SAEs reported in the investigational and crossover subjects at Month 60. A similar trend was observed in the SSI rates reported across all three treatment groups. PMA P240043: FDA Summary of Safety and Effectiveness Data {32} Table 14: Comparison of Summary of Safety Events up to 60 Months – Investigational and Control mITT-Followed and Crossover | | Investigational (N=182) | | | Control (N=97) | | | Crossover (N=59) | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Events | n | % | Events | n | % | Events | n | % | | Any adverse event | 1033 | 175 | 96.2% | 507 | 91 | 93.8% | 269 | 56 | 94.9% | | Any implant/surgical procedure associated AE | 6 | 6 | 3.3% | 0 | 0 | 0.0% | 2 | 2 | 3.4% | | Any implant only associated AE | 4 | 4 | 2.2% | 0 | 0 | 0.0% | 2 | 2 | 3.4% | | Any surgical procedure only associated AE | 46 | 44 | 24.2% | 0 | 0 | 0.0% | 27 | 24 | 40.7% | | Any nonoperative treatment associated AE | 0 | 0 | 0.0% | 2 | 2 | 2.1% | 0 | 0 | 0.0% | | Any serious AE | 110 | 75 | 41.2% | 58 | 47 | 48.5% | 32 | 24 | 40.7% | | Any implant/surgical procedure associated SAE | 3 | 3 | 1.6% | 0 | 0 | 0.0% | 1 | 1 | 1.7% | | Any implant only associated SAE | 2 | 2 | 1.1% | 0 | 0 | 0.0% | 0 | 0 | 0.0% | | Any surgical procedure only associated SAE | 10 | 10 | 5.5% | 0 | 0 | 0.0% | 6 | 6 | 10.2% | | Any nonoperative treatment associated SAE | 0 | 0 | 0.0% | 2 | 2 | 2.1% | 0 | 0 | 0.0% | | Spinous Process Fracture | 14 | 14 | 7.7% | 0 | 0 | 0.0% | 6 |… --- **Source:** [https://fda.innolitics.com/device/P240043](https://fda.innolitics.com/device/P240043) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. 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