LAUSR

I pioneered by Robinson and Smith in 1955, anterior cervical discectomy and fusion (ACDF) has long been considered the gold standard for treatment of patients with cervical radiculopathy and myelopathy and has reliably demonstrated good clinical outcomes.1 Despite these successes, dysphagia, adjacent segment degeneration (ASD), and pseudarthrosis are the most common complications of this procedure. Cervical disk arthroplasty (CDA) was developed as an alternative to ACDF, with the theory that improved spinal kinematics may lead to a decreased risk of ASD.2 CDA has been shown to provide pain relief and functional improvements similar to, or superior to ACDF.3 However, complications of CDA such as heterotopic ossification, migration or subsidence of the implant, and wear debris are specific to CDA and are not generally found in patients who undergo ACDF.4 As the newer CDA devices sought regulatory approval via the Food and Drug Administration, each device manufacturer-funded investigational device exemption studies that compare CDA to ACDF.5–7 In this review, we argue that industry-funded randomized controlled trials (RCTs) are biased in favor of CDA over ACDF for symptomatic cervical disk disease due to publication bias, external validity bias, and confirmation bias. Publication bias in medical research refers to the concept that studies with positive results are more commonly accepted for publication in peer-reviewed journals.8 In orthopedic surgery, it has been shown that up to 26% of RCTs are industry-funded and that these studies preferentially report favorable outcomes for the new device 85% of the time, significantly greater than the nonindustry-funded studies.9 Because of publication bias, a meta-analysis of the available CDA literature has been shown to be lacking smaller negative or equivalent results studies, making the conclusions of these studies difficult to interpret.10 RCTs which investigate CDA compared with ACDF exhibit publication bias where specific subanalysis of the data is chosen to highlight positive results. In a prospective RCT by Zigler et al,11 the ProDisc-C was compared with ACDF at a 5-year follow-up. The study included 209 patients from across 13 sites split into 103 ProDisc-C and 106 ACDF treatment groups. At 5 years, the authors reported that patients who received the CDA had similar outcomes and fewer complications with CDA compared with ACDF. Delamarter et al12 performed an additional subanalysis of this same 5-year prospective data. They determined that the ProDisc-C had significantly lower rates of secondary surgery at the index and adjacent levels than patients who underwent ACDF (97.1% vs. 85.5%, P=0.0079).12 The Discover artificial disk replacement investigational device exemption study is another example of a trial that split its data into subgroups to only highlight positive findings. A subanalysis of the data investigated preoperative radiographic variables and found that decreased preoperative disk space height was predictive of negative outcomes.13 In addition, available unpublished data from (https://clinicaltrials.gov/ct2/show/ results/NCT00700739?view=results) show that only 33% of patients with CDA had a clinically significant improvement in Neck Disability Index (NDI), compared with 91% of patients who received an ACDF.14 External validity refers to the specific conditions used as inclusion criteria for clinical trials, and the generalizability of Received for publication September 19, 2019; accepted November 18, 2019. From the Department of Orthopaedic Surgery, Rothman Institute, Thomas Jefferson University, Philadelphia, PA. Dr Schroeder has received funds to travel from AO Spine and Medtronic. Dr Vaccaro has consulted or has done independent contracting for DePuy, Medtronic, Stryker Spine, Globus, Stout Medical, Gerson Lehrman Group, Guidepoint Global, Medacorp, Innovative Surgical Design, Orthobullets, Ellipse, and Vertex. He has also served on the scientific advisory board/board of directors/committees for Flagship Surgical, AO Spine, Innovative Surgical Design, and Association of Collaborative Spine Research. Dr Vaccaro has received royalty payments from Medtronic, Stryker Spine, Globus, Aesculap, Thieme, Jaypee, Elsevier, and Taylor Francis/Hodder and Stoughton. He has stock/stock option ownership interests in Replication Medica, Globus, Paradigm Spine, Stout Medical, Progressive Spinal Technologies, Advanced Spinal Intellectual Properties, Spine Medica, Computational Biodynamics, Spinology, In Vivo, Flagship Surgical, Cytonics, Bonovo Orthopaedics, Electrocore, Gamma Spine, Location Based Intelligence, FlowPharma, R.S.I., Rothman Institute and Related Properties, Innovative Surgical Design, and Avaz Surgical. He has also served as deputy editor/editor of Spine. In addition, Dr Vaccaro has also provided expert testimony. The remaining authors declare no conflict of interest. Reprints: Matthew S. Galetta, BA, Department of Orthopaedic Surgery, Rothman Institute, Thomas Jefferson University, 925 Chestnut Street, 5th Floor, Philadelphia, PA 19107 (e-mail: [email protected]). Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. CONTROVERSIES IN SPINE SURGERY