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Selph SS, Skelly AC, Jungbauer RM, et al. Cervical Degenerative Disease Treatment: A Systematic Review [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2023 Nov. (Comparative Effectiveness Review, No. 266.)

Cover of Cervical Degenerative Disease Treatment: A Systematic Review

Cervical Degenerative Disease Treatment: A Systematic Review [Internet].

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Appendix AMethods

A1.1. Search Strategy

The searches were conducted by Key Question, with the exception of EMBASE.

Database: Ovid MEDLINE(R) ALL <1946 to February 15, 2023>

Search Strategy for KQ1–2:

------------------------------------------------------------

  1. Spinal Cord Compression/
  2. “spinal cord compression”.ti,ab.
  3. exp Cervical Vertebrae/
  4. 3 and degenerat*.ti,ab.
  5. (cervical and degenerat*).ti,ab.
  6. (1 or 2) and (4 or 5)
  7. su.fs.
  8. (surgery or surgical).ti,ab.
  9. 6 and (7 or 8)
  10. limit 9 to (comparative study or controlled clinical trial or meta analysis or randomized controlled trial or “systematic review”)
  11. (random* or control* or NRSI or observational or prospective or retrospective or review or systematic or “meta analysis” or “metaanalysis”).ti,ab,pt.
  12. 9 and 11
  13. 10 or 12
  14. (Animals/ or Models, Animal/ or Disease Models, Animal/) not Humans/
  15. ((animal or animals or avian or bird or birds or bovine or canine or cow* or dog or dogs or cat or cats or feline or hamster* or horse* or lamb or lamb* or mouse or mice or monkey or monkeys or murine or pig or piglet* or pigs or porcine or primate* or rabbit* or rat or rats or rodent* or songbird* or veterinar*) not (human* or patient*)).ti,kf,jw.
  16. or/14-15
  17. 13 not 16
  18. limit 17 to yr=“1980 -Current”

Database: Ovid MEDLINE(R) ALL <1946 to February 15, 2023>

Search Strategy for KQ3–4:

------------------------------------------------------------

  1. exp Cervical Vertebrae/su [Surgery]
  2. 1 and degenerat*.ti,ab.
  3. (cervical and degenerat*).ti,ab.
  4. su.fs.
  5. (surgery or surgical).ti,ab.
  6. 3 and (4 or 5)
  7. 2 or 6
  8. limit 7 to (comparative study or controlled clinical trial or meta analysis or randomized controlled trial or “systematic review”)
  9. (random* or control* or NRSI or observational or prospective or retrospective or review or systematic or “meta analysis” or “metaanalysis”).ti,ab,pt.
  10. 7 and 9
  11. 8 or 10
  12. (Animals/ or Models, Animal/ or Disease Models, Animal/) not Humans/
  13. ((animal or animals or avian or bird or birds or bovine or canine or cow* or dog or dogs or cat or cats or feline or hamster* or horse* or lamb or lamb* or mouse or mice or monkey or monkeys or murine or pig or piglet* or pigs or porcine or primate* or rabbit* or rat or rats or rodent* or songbird* or veterinar*) not (human* or patient*)).ti,kf,jw.
  14. or/12-13
  15. 11 not 14
  16. limit 15 to yr=“1980 -Current”

Database: Ovid MEDLINE(R) ALL <1946 to February 15, 2023>

Search Strategy for KQ5:

------------------------------------------------------------

  1. Radiculopathy/su [Surgery]
  2. radiculopathy.ti,ab.
  3. su.fs.
  4. (surgery or surgical).ti,ab.
  5. 2 and (3 or 4)
  6. 1 or 5
  7. (anterior and posterior).ti,ab.
  8. 6 and 7
  9. limit 8 to (comparative study or controlled clinical trial or meta analysis or randomized controlled trial or “systematic review”)
  10. (random* or control* or NRSI or observational or prospective or retrospective or review or systematic or “meta analysis” or “metaanalysis”).ti,ab,pt.
  11. 8 and 10
  12. 9 or 11
  13. (Animals/ or Models, Animal/ or Disease Models, Animal/) not Humans/
  14. ((animal or animals or avian or bird or birds or bovine or canine or cow* or dog or dogs or cat or cats or feline or hamster* or horse* or lamb or lamb* or mouse or mice or monkey or monkeys or murine or pig or piglet* or pigs or porcine or primate* or rabbit* or rat or rats or rodent* or songbird* or veterinar*) not (human* or patient*)).ti,kf,jw.
  15. or/13-14
  16. 12 not 15
  17. limit 16 to yr=“2006 -Current”

Database: Ovid MEDLINE(R) ALL <1946 to February 15, 2023>

Search Strategy for KQ6:

------------------------------------------------------------

  1. exp Cervical Vertebrae/su [Surgery]
  2. 1 and degenerat*.ti,ab.
  3. (cervical and degenerat*).ti,ab.
  4. su.fs.
  5. (surgery or surgical).ti,ab.
  6. 3 and (4 or 5)
  7. 2 or 6
  8. (anterior and posterior).ti,ab.
  9. 7 and 8
  10. limit 9 to (comparative study or controlled clinical trial or meta analysis or randomized controlled trial or “systematic review”)
  11. (random* or control* or NRSI or observational or prospective or retrospective or review or systematic or “meta analysis” or “metaanalysis”).ti,ab,pt.
  12. 9 and 11
  13. 10 or 12
  14. (Animals/ or Models, Animal/ or Disease Models, Animal/) not Humans/
  15. ((animal or animals or avian or bird or birds or bovine or canine or cow* or dog or dogs or cat or cats or feline or hamster* or horse* or lamb or lamb* or mouse or mice or monkey or monkeys or murine or pig or piglet* or pigs or porcine or primate* or rabbit* or rat or rats or rodent* or songbird* or veterinar*) not (human* or patient*)).ti,kf,jw.
  16. or/14-15
  17. 13 not 16
  18. limit 17 to yr=“2006 -Current”

Database: Ovid MEDLINE(R) ALL <1946 to February 15, 2023>

Search Strategy for KQ7:

------------------------------------------------------------

  1. Spinal Cord Diseases/
  2. (spondylo* or cervical or myelopathy).ti.
  3. 1 and 2
  4. ((spondylo* or cervical) and myelopathy).ti,ab.
  5. 3 or 4
  6. Laminectomy/ or Laminoplasty/
  7. (laminectomy or laminoplasty).ti,ab.
  8. 6 or 7
  9. 5 and 8
  10. limit 9 to (comparative study or controlled clinical trial or meta analysis or randomized controlled trial or “systematic review”)
  11. (random* or control* or NRSI or observational or prospective or retrospective or review or systematic or “meta analysis” or “metaanalysis”).ti,ab,pt.
  12. 9 and 11
  13. 10 or 12
  14. (Animals/ or Models, Animal/ or Disease Models, Animal/) not Humans/
  15. ((animal or animals or avian or bird or birds or bovine or canine or cow* or dog or dogs or cat or cats or feline or hamster* or horse* or lamb or lamb* or mouse or mice or monkey or monkeys or murine or pig or piglet* or pigs or porcine or primate* or rabbit* or rat or rats or rodent* or songbird* or veterinar*) not (human* or patient*)).ti,kf,jw.
  16. or/14-15
  17. 13 not 16
  18. limit 17 to yr=“2006 -Current”

Database: Ovid MEDLINE(R) ALL <1946 to February 15, 2023>

Search Strategy for KQ8:

------------------------------------------------------------

  1. Spinal Cord Diseases/
  2. 1 and myelopathy.ti.
  3. Radiculopathy/
  4. (spondylo* or cervical).ti.
  5. (2 or 3) and 4
  6. ((spondylo* or cervical) and (radiculopathy or myelopathy)).ti,ab.
  7. 5 or 6
  8. Arthroplasty/ and Diskectomy/
  9. (arthroplasty and (discectomy or diskectomy)).ti,ab.
  10. 8 or 9
  11. 7 and 10
  12. limit 11 to (comparative study or controlled clinical trial or meta analysis or randomized controlled trial or “systematic review”)
  13. (random* or control* or NRSI or observational or prospective or retrospective or review or systematic or “meta analysis” or “metaanalysis”).ti,ab,pt.
  14. 11 and 13
  15. 12 or 14
  16. (Animals/ or Models, Animal/ or Disease Models, Animal/) not Humans/
  17. ((animal or animals or avian or bird or birds or bovine or canine or cow* or dog or dogs or cat or cats or feline or hamster* or horse* or lamb or lamb* or mouse or mice or monkey or monkeys or murine or pig or piglet* or pigs or porcine or primate* or rabbit* or rat or rats or rodent* or songbird* or veterinar*) not (human* or patient*)).ti,kf,jw.
  18. or/16-17
  19. 15 not 18
  20. limit 19 to yr=“2006 -Current”

Database: Ovid MEDLINE(R) ALL <1946 to February 15, 2023>

Search Strategy for KQ9:

------------------------------------------------------------

  1. Diskectomy/
  2. (discectomy or diskectomy).ti,ab.
  3. (1 or 2) and cervical.ti,ab.
  4. 3 and anterior.ti,ab.
  5. (interbody or graft* or type or device* or “standalone” or “stand alone” or traditional or plat* or cage*).ti,ab.
  6. 4 and 5
  7. limit 6 to (comparative study or controlled clinical trial or meta analysis or randomized controlled trial or “systematic review”)
  8. (random* or control* or NRSI or observational or prospective or retrospective or review or systematic or “meta analysis” or “metaanalysis”).ti,ab,pt.
  9. 6 and 8
  10. 7 or 9
  11. (Animals/ or Models, Animal/ or Disease Models, Animal/) not Humans/
  12. ((animal or animals or avian or bird or birds or bovine or canine or cow* or dog or dogs or cat or cats or feline or hamster* or horse* or lamb or lamb* or mouse or mice or monkey or monkeys or murine or pig or piglet* or pigs or porcine or primate* or rabbit* or rat or rats or rodent* or songbird* or veterinar*) not (human* or patient*)).ti,kf,jw.
  13. or/11-12
  14. 10 not 13
  15. limit 14 to yr=“2006 -Current”

Database: Ovid MEDLINE(R) ALL <1946 to February 15, 2023>

Search Strategy for KQ10:

------------------------------------------------------------

  1. Pseudarthrosis/
  2. pseudarthrosis.ti,ab.
  3. 1 or 2
  4. cervical.ti,ab.
  5. 3 and 4
  6. Arthrodesis/
  7. arthrodesis.ti,ab.
  8. 6 or 7
  9. (anterior or posterior).ti,ab.
  10. 5 and (8 or 9)
  11. limit 10 to (comparative study or controlled clinical trial or meta analysis or randomized controlled trial or “systematic review”)
  12. (random* or control* or NRSI or observational or prospective or retrospective or review or systematic or “meta analysis” or “metaanalysis”).ti,ab,pt.
  13. 10 and 12
  14. 11 or 13
  15. (Animals/ or Models, Animal/ or Disease Models, Animal/) not Humans/
  16. ((animal or animals or avian or bird or birds or bovine or canine or cow* or dog or dogs or cat or cats or feline or hamster* or horse* or lamb or lamb* or mouse or mice or monkey or monkeys or murine or pig or piglet* or pigs or porcine or primate* or rabbit* or rat or rats or rodent* or songbird* or veterinar*) not (human* or patient*)).ti,kf,jw.
  17. 15 or 16
  18. 14 not 17
  19. limit 18 to yr=“2006 -Current”

Database: Ovid MEDLINE(R) ALL <1946 to February 15, 2023>

Search Strategy for KQ11:

------------------------------------------------------------

  1. Spinal Cord Diseases/dg [Diagnostic Imaging]
  2. 1 and myelopathy.ti,ab.
  3. ((cervical or spondylo*) and myelopathy).ti,ab.
  4. 2 or 3
  5. Magnetic Resonance Imaging/
  6. (“magnetic resonance imag*” or “mri”).ti,ab.
  7. (“pre operative” or “preoperative”).ti,ab.
  8. (5 or 6) and 7
  9. limit 8 to “prognosis (maximizes sensitivity)”
  10. 4 and 9
  11. limit 10 to yr=“1980 -Current”

Database: Ovid MEDLINE(R) ALL <1946 to February 15, 2023>

Search Strategy for KQ12:

------------------------------------------------------------

  1. Pseudarthrosis/dg [Diagnostic Imaging]
  2. pseudarthrosis.ti,ab.
  3. Diagnostic Imaging/
  4. dg.fs.
  5. (image or imaging).ti,ab.
  6. 2 and (or/3-5)
  7. 1 or 6
  8. exp “Sensitivity and Specificity”/
  9. (sensitivity or specificity or accuracy or predict* or “reference standard” or “gold standard”).ti,ab.
  10. “reproducibility of results”/
  11. 8 or 9 or 10
  12. 7 and 11
  13. limit 12 to yr=“1980 -Current”

Database: Ovid MEDLINE(R) ALL <1946 to February 15, 2023>

Search Strategy for KQ13:

------------------------------------------------------------

  1. Spinal Cord Diseases/
  2. 1 and myelopathy.ti,ab.
  3. ((cervical or spondylo*) and myelopathy).ti,ab.
  4. 2 or 3
  5. exp Monitoring, Intraoperative/
  6. (intraoperat* and monitor*).ti,ab.
  7. (neuromonitor* or somatosensory or “motor evoked potential”).ti,ab.
  8. 7 and intraoperat*.ti,ab.
  9. 5 or 6 or 8
  10. 4 and 9
  11. limit 10 to yr=“2006 -Current”

Database: EMBASE

Search Strategy:

------------------------------------------------------------

(‘cervical degenerative disc disease’/exp OR ‘cervical degenerative disease’/exp OR ‘cervical degenerative’:ab,ti OR ((‘cervicobrachial neuralgia’/exp OR ‘cervicobrachial neuralgia’) AND degenerative) OR (myelopathy AND degenerative) OR (pseudarthrosis AND cervical AND fusion AND (anterior OR posterior))) AND (‘diagnostic imaging’ OR ‘nuclear magnetic resonance imaging’ OR ‘neuromonitoring’) AND (‘prognosis’ OR ‘predictive value’ OR ‘predictive validity’ OR ‘sensitivity and specificity’) AND [embase]/lim NOT ([embase]/lim AND [medline]/lim)

Database: EBM Reviews - Cochrane Database of Systematic Reviews <2005 to February 2023>

Search Strategy:

------------------------------------------------------------

  1. (spine or spinal or radiculopathy or myelopathy).ti.
  2. (cervical and degenerat*).ti,ab.
  3. 1 or 2
  4. limit 3 to full systematic reviews

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <February 2023>

Search Strategy for KQ1–2:

------------------------------------------------------------

  1. Spinal Cord Compression/
  2. “spinal cord compression”.ti,ab.
  3. exp Cervical Vertebrae/
  4. 3 and degenerat*.ti,ab.
  5. (cervical and degenerat*).ti,ab.
  6. (1 or 2) and (4 or 5)
  7. su.fs.
  8. (surgery or surgical).ti,ab.
  9. 6 and (7 or 8)
  10. limit 9 to yr=“1980 -Current”

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <February 2023>

Search Strategy for KQ3–4:

------------------------------------------------------------

  1. Cervical Vertebrae/ (1027)
  2. 1 and degenerat*.ti,ab.
  3. (cervical and degenerat*).ti,ab.
  4. su.fs.
  5. (surgery or surgical).ti,ab.
  6. (2 or 3) and (4 or 5)
  7. limit 6 to yr=“1980 -Current”

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <February 2023>

Search Strategy for KQ5:

------------------------------------------------------------

  1. Radiculopathy/
  2. radiculopathy.ti,ab.
  3. su.fs.
  4. (surgery or surgical).ti,ab.
  5. (1 or 2) and (3 or 4)
  6. (anterior and posterior).ti,ab.
  7. 5 and 6
  8. limit 7 to yr=“2006 -Current”

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <February 2023>

Search Strategy for KQ6:

------------------------------------------------------------

  1. Cervical Vertebrae/
  2. 1 and degenerat*.ti,ab.
  3. (cervical and degenerat*).ti,ab.
  4. su.fs.
  5. (surgery or surgical).ti,ab.
  6. (2 or 3) and (4 or 5)
  7. (anterior and posterior).ti,ab.
  8. 6 and 7
  9. limit 8 to yr=“2006 -Current”

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <February 2023>

Search Strategy for KQ7:

------------------------------------------------------------

  1. Spinal Cord Diseases/
  2. (spondylo* or cervical or myelopathy).ti.
  3. 1 and 2
  4. ((spondylo* or cervical) and myelopathy).ti,ab.
  5. 3 or 4
  6. Laminectomy/ or Laminoplasty/
  7. (laminectomy or laminoplasty).ti,ab.
  8. 5 and (6 or 7)
  9. limit 8 to yr=“2006 -Current”

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <February 2023>

Search Strategy for KQ8:

------------------------------------------------------------

  1. Spinal Cord Diseases/
  2. 1 and myelopathy.ti.
  3. Radiculopathy/
  4. (spondylo* or cervical).ti.
  5. (2 or 3) and 4
  6. ((spondylo* or cervical) and (radiculopathy or myelopathy)).ti,ab.
  7. 5 or 6
  8. Arthroplasty/ and Diskectomy/
  9. (arthroplasty and (discectomy or diskectomy)).ti,ab.
  10. 8 or 9
  11. 7 and 10
  12. limit 11 to yr=“2006 -Current”

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <February 2023>

Search Strategy for KQ9:

------------------------------------------------------------

  1. Diskectomy/
  2. (discectomy or diskectomy).ti,ab.
  3. (1 or 2) and cervical.ti,ab.
  4. 3 and anterior.ti,ab.
  5. (interbody or graft* or type or device* or “standalone” or “stand alone” or traditional or plat* or cage*).ti,ab.
  6. 4 and 5
  7. limit 6 to yr=“2006 -Current”

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <February 2023>

Search Strategy for KQ10:

------------------------------------------------------------

  1. Pseudarthrosis/
  2. pseudarthrosis.ti,ab.
  3. 1 or 2
  4. cervical.ti,ab.
  5. 3 and 4
  6. Arthrodesis/
  7. arthrodesis.ti,ab.
  8. 6 or 7
  9. (anterior or posterior).ti,ab.
  10. 5 and (8 or 9)
  11. limit 10 to yr=“2006 -Current”

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <February 2023>

Search Strategy for KQ11:

------------------------------------------------------------

  1. Spinal Cord Diseases/
  2. 1 and myelopathy.ti,ab.
  3. ((cervical or spondylo*) and myelopathy).ti,ab.
  4. 2 or 3
  5. Magnetic Resonance Imaging/
  6. (“magnetic resonance imag*” or “mri”).ti,ab.
  7. (“pre operative” or “preoperative”).ti,ab.
  8. (5 or 6) and 7
  9. 4 and 8
  10. limit 9 to yr=“1980 -Current”

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <February 2023>

Search Strategy for KQ12:

------------------------------------------------------------

  1. Pseudarthrosis/
  2. pseudarthrosis.ti,ab.
  3. Diagnostic Imaging/
  4. dg.fs.
  5. (image or imaging).ti,ab.
  6. (1 or 2) and (or/3-5)
  7. exp “Sensitivity and Specificity”/
  8. (sensitivity or specificity or accuracy or predict* or “reference standard” or “gold standard”).ti,ab.
  9. “reproducibility of results”/
  10. 7 or 8 or 9
  11. 6 and 10

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <February 2023>

Search Strategy for KQ13:

------------------------------------------------------------

  1. Spinal Cord Diseases/
  2. 1 and myelopathy.ti,ab.
  3. ((cervical or spondylo*) and myelopathy).ti,ab.
  4. 2 or 3
  5. exp Monitoring, Intraoperative/
  6. (intraoperat* and monitor*).ti,ab.
  7. (neuromonitor* or somatosensory or “motor evoked potential”).ti,ab.
  8. 7 and intraoperat*.ti,ab.
  9. 5 or 6 or 8
  10. 4 and 9

A2.1. Expanded Methods

2.1.1. Literature Search Strategy

We conducted electronic searches in Ovid MEDLINE®, EMBASE, and Cochrane CENTRAL from 1980 to February 15, 2023 (see Appendix A1.1 for full strategies). For Key Questions that compare operative approaches, we searched databases for studies published after 2006 (studies published in 2007 or earlier were included in the 2009 guidelines).1 Additionally, we reviewed all studies included in the 2009 guidelines for inclusion in this review.1 For Key Questions not covered by the 2009 guidelines (e.g., operative versus nonoperative studies, neuromonitoring studies) we searched the databases from 1980 to the present in order to identify relevant, earlier studies based on when technologies such as neuromonitoring and advanced imaging were first used in research trials. Reference lists of included systematic reviews were screened for additional studies and relevant references were carried forward. A Federal Register notification for a Supplemental Evidence and Data for Systematic review (SEADS) portal was posted from August 12th to September 12th, 2022, for submission of unpublished studies.

2.1.1.1. PICOTS

Criteria were established a priori to determine eligibility for inclusion and exclusion of abstracts in accordance with the Agency for Healthcare Research and Quality (AHRQ) Methods Guide for Effectiveness and Comparative Effectiveness Reviews (hereafter the “AHRQ Methods Guide”).2 Study eligibility criteria for this CER were based on the population, intervention, comparisons, outcomes, timing, settings, and study designs of interest (PICOTS) framework and the Key Questions. The population of interest was adults (aged ≥18 years) with symptomatic cervical degenerative disease (e.g., pain, radiculopathy, myelopathy) for all Key Questions except for Key Question 1, which included asymptomatic patients. We also captured effectiveness and harms of surgery based on patient characteristics, disease characteristics and radiographic characteristics, where available. Details regarding the PICOTS are summarized in Table A-1. Specific outcomes for each management approach considered are described in detail in Table A-1.

For this review, management included cervical spine surgery, non-surgical treatments, intraoperative monitoring, imaging to identify symptomatic pseudarthrosis (vertebrae do not fuse successfully) after cervical fusion surgery, and preoperative MRI to predict neurological recovery in myelopathy. Comparisons included any eligible intervention, placebo, waitlist, or active control.

Study designs considered for inclusion were comparative studies of any design including trials of any size and observational studies (N≥50). For Key Questions 11–12 and studies focused on harms as the primary outcome, we considered large intervention series (N≥50) eligible, including those with single arms where everyone received the same intervention. We reviewed existing systematic reviews and included their results if appropriate. References lists of systematic reviews were also used to identify relevant studies. Descriptive studies with no outcome data or studies that included only data from one point in time (cross-sectional) were not included. For Key Questions 1–10, pre-post single-arm studies and systematic reviews published prior to 2007 were excluded, as these studies would have been captured in the guidelines. Also excluded were commentaries, letters, and narrative reviews, as were studies published only as conference abstracts. Inclusion was restricted to English-language articles, and studies of nonhuman subjects were excluded (Appendix B).

To ensure accuracy, all excluded abstracts were dual reviewed by two investigators. Each full-text article was independently reviewed for eligibility by two team members. All disagreements were resolved through a consensus process between investigators.

Contextual Questions were addressed without presepecified inclusion criteria; we used studies identified in our main searches to answer the Contextual Questions.

Table A-1PICOTS – inclusion and exclusion criteria

PICOTIncludeExclude
Population
  • Age 18 and above with symptomatic cervical degenerative disease (e.g., pain, radiculopathy, myelopathy) for all KQs except for KQ1, which includes asymptomatic patients
  • Effectiveness and harms of surgery based on patient characteristics, disease characteristics and radiographic characteristics (e.g., age, gender, comorbidities [e.g., comorbid lumbar disease, autoimmune disease, neurological disease, mental illness, Down’s syndrome], severity of cervical degenerative disease, Frailty Index, sagittal vertical aspect, degree of kyphosis, prior treatment [e.g., bracing, traction, medications, massage, acupuncture, injections, chiropractic care, spinal manipulation], duration of pain, skill of surgeon)
  • Younger than 18 years
  • Patients without cervical degenerative disease
  • Nonhumans
Interventions
  • Cervical spine surgery (e.g., discectomy, disc replacement, fusion up to T2, arthroplasty, laminectomy, laminoplasty, corpectomy, cervical hybrid surgery, foraminotomy, ACDF cage vs. ACDF cage + plate)
  • Non-surgical treatments (e.g., heat, exercise, acupuncture, drugs, radiofrequency ablation, steroid injections, Botox® for neck pain, psychological strategies [e.g., cognitive behavioral therapy], occupational therapy, multidisciplinary rehabilitation)
  • Intraoperative neuromonitoring
  • Imaging to identify symptomatic pseudarthrosis after cervical fusion surgery
  • Preoperative MRI to predict neurologic recovery in myelopathy
  • Preoperative imaging using CT or plain films
  • KQ4: intraoperative therapy
  • KQ7: laminectomy without fusion
Comparators
  • Any included intervention
  • Placebo, waitlist, active control
  • No comparator (KQs 11 and 12)
  • Nonoperative intervention versus nonoperative intervention without surgical comparator
Outcomes
  • Pain, sensory function, motor function, gait, quality of life (e.g., VAS, NRS, NDI, SF-36, SF-12, EQ-5Dm, mJOA score, Nurick score, MDI, PROMIS-29), dysphagia scales, return to work
  • Fusion rate, reoperation rate
  • Harms (e.g., withdrawals due to adverse events, serious adverse events, new symptomatic adjacent segment disease, postoperative infection, device failure, ossification of the posterior ligament, development of kyphotic deformity)
  • Sensitivity and specificity of imaging after cervical fusion surgery
  • Nonvalidated instruments
Timing
  • All time periods
None
Setting
  • Inpatient, outpatient, ambulatory surgical centers
None
Study types and designs
  • RCTs, prospective trials and retrospective observational studies with a control group (study N≥50), current systematic reviews
  • KQs 11–13 and studies focused on harms as a primary outcome: large intervention series (N≥50; can be single arm, but everyone received the same intervention)
  • KQ1–10: pre-post single-arm studies, case series (everyone selected based on outcome), case reports, systematic reviews published prior to 2007
  • KQ11–13: pre-post non-intervention studies, case series, case reports, systematic reviews published prior to 2007
Language
  • English language
  • Non-English

Abbreviations: ACDF = anterior cervical discectomy and fusion; CT = computed tomography; EQ-5D = EuroQol-5 dimension instrument; KQ = Key Question; MDI = myelopathy disability index; MRI = magnetic resonance imaging; mJOA = modified Japanese orthopedic association scale; NDI = neck disability index; NRS = numerical pain rating scale; PROMIS-29 = patient reported outcome measurement information system; RCT = randomized controlled trial; QOL = quality of life; SF = short form health survey (12 or 36 items); VAS = visual analogue scale

2.1.2. Data Abstraction and Data Management

Dual review of abstracts was conducted using prespecified inclusion criteria and DistillerSR software version 2.35 (https://www.distillersr.com/). Discrepancies were resolved by discussion and consensus. Investigators tracked results in EndNote version 20.1 (Thomson Reuters, New York, NY). For studies meeting inclusion criteria, evidence tables were constructed with the following data: study design, author, year, setting, country, sample size, patient characteristics (e.g., age, gender, obesity, number of vertebral levels involved, severity of radiculopathy and/or myelopathy), effectiveness-related outcomes (e.g., validated pain, function and quality of life measures), as well as treatment-related adverse effects/harms) and results relevant to each Key Question as outlined in the previous PICOTS section (Appendix C).

2.1.3. Risk of Bias Assessment of Individual Studies

Predefined criteria were used to assess the risk of bias (also referred to as quality or internal validity) for each individual included study, using criteria appropriate for the study design (Table A-2 and Appendix D1.1). Controlled trials and observational studies were assessed using a priori established criteria consistent with the AHRQ-Evidence-based Practice Center (EPC) approach recommended in the chapter, “Assessing the Risk of Bias of Individual Studies,” described in the AHRQ Methods Guide.2 RCTs were evaluated using criteria and methods developed by the Cochrane Back and Neck Group,3 nonrandomized studies of interventions (NRSI) and other observational studies of interventions were evaluated using criteria developed by the U.S. Preventive Services Task Force,4 and followed the approach recommended in the AHRQ Methods Guide chapter “Assessing the Risk of Bias of Individual Studies When Comparing Medical Interventions.”2 For randomized controlled trials (RCTs), we focused on randomization, allocation concealment, analysis according to randomized groups (intent-to-treat analysis), and attrition. NRSIs that controlled for potential prognostic variables were included to fill gaps in evidence when RCTs did not sufficient address the Key Questions.

Each study was independently reviewed for risk of bias by two team members. Any disagreements were resolved through consensus. Based on the risk of bias assessment, included studies were rated as having “low,” “moderate,” or “high” risk of bias (Appendix D2.1). Studies rated high risk of bias were not excluded a priori, but were considered to be less reliable than low or moderate risk of bias studies when synthesizing the evidence.

Table A-2Criteria for grading the risk of bias of individual studies

RatingDescription and Criteria
Low

Least risk of bias, results generally considered valid

Employ valid methods for selection, inclusion, and allocation of patients to treatment; report similar baseline characteristics in different treatment groups; clearly describe attrition and have low attrition; use appropriate means for preventing bias (e.g., blinding of patients, care providers, and outcomes assessors); and use appropriate analytic methods (e.g., intention-to-treat analysis)

Moderate

Susceptible to some bias but not enough to necessarily invalidate results

May not meet all criteria for low risk of bias, but no flaw is likely to cause major bias; the study may be missing information making it difficult to assess limitations and potential problems

Category is broad; studies with this rating will vary in strengths and weaknesses; some studies rated moderate risk of bias are likely to be valid, while others may be only possibly valid

High

Significant flaws that imply biases of various kinds that may invalidate results; “fatal flaws” in design, analysis or reporting; large amounts of missing information; discrepancies in reporting; or serious problems with intervention delivery

Studies are at least as likely to reflect flaws in the study design or execution as the true difference between the compared interventions

Considered to be less reliable than studies rated moderate or low risk of bias when synthesizing the evidence, particularly if discrepancies between studies are present

Table A-2 is taken from the Cervical Degenerative Disease Protocol, published online at https://effectivehealthcare.ahrq.gov/sites/default/files/product/pdf/cervical-degenerative-protocol.pdf

Because most studies were rated moderate risk of bias, we called out in the text studies rated high risk of bias as extra caution should be exercised when drawing conclusions from such studies.

2.1.4. Data Analysis and Synthesis

Evidence tables identify study characteristics, results of interest, and risk of bias ratings for all included studies and summary tables highlight the main findings. Studies were reviewed and highlighted using a hierarchy-of-evidence approach, where the best evidence is the focus of the synthesis for each Key Question. Since the Key Questions varied in nature and scope, the approach to synthesis also varied. We analyzed the evidence according to Key Question, using both qualitative (narrative) and where possible quantitative (meta-analysis) methods. RCTs were prioritized and studies with lower risk of bias ratings were given more weight in our synthesis for each clinical indication and outcome.

Meta-analyses were conducted to obtain more precise effect estimates for comparative effectiveness of various interventions for cervical spine. To determine the appropriateness of meta-analysis, we considered clinical and methodological diversity and assessed statistical heterogeneity. We conducted meta-analyses of randomized and nonrandomized evidence separately. For binary outcomes (e.g., overall success, neurological success, re-operation, fusion), risk ratio (RR) was used as the effect measure. For continuous outcomes (e.g. NDI, neck or arm pain, Japanese Orthopaedic Association Scale [JOA] scores, quality of life), mean difference (MD) was used as the effect measure as the studies reported outcomes using the same scale, or the outcomes could be converted to the same scale (e.g. pain, converted to 0-100 scale) (Table A-3). Adjusted mean differences between interventions were used if reported; otherwise, MD was calculated using the follow-up score if reported and then the change score from the baseline. When the reported measure of dispersion for each intervention group was not specified as standard deviation (SD) or standard error (SE), judgement was made based on the reported p-values for comparing the intervention groups and the magnitude of dispersion measures of similar studies. When SD was not reported, or could not be calculated from the reported data, it was imputed using the average coefficient of variation from the other included studies reporting the same outcome.

Table A-3Definition of effect sizes

Effect SizeDefinition
Small effect

MD 0.5 to 1.0 points on a 0 to 10-point scale, 5 to 10 points on a 0 to 100-point scale

SMD 0.2 to 0.5

RR/OR 1.2 to 1.4

Moderate effect

MD >1 to 2 points on a 0 to10-point scale, >10 to 20 points on a 0 to 100-point scale

SMD >0.5 to 0.8

RR/OR 1.5 to 1.9

Large effect

MD >2 points on a 0 to10-point scale, >20 points on a 0 to 100-point scale

SMD >0.8

RR/OR ≥2.0

MD = mean difference; OR = odds ratio; RR = relative risk; SMD = standardized mean difference

Table A-3 taken from the Cervical Degenerative Disease Protocol, published online at https://effectivehealthcare.ahrq.gov/sites/default/files/product/pdf/cervical-degenerative-protocol.pdf

A random effects model based on the profile likelihood method5 was used to obtain pooled RR and MD. When applicable, the primary analyses were stratified by the length of follow up: short term (≤ 6 months), intermediate term (6 to 60 months), long term (> 60 months), or using the actual follow up time. For arm pain success and arm pain score, when studies reported data from each arm separately, we conducted an optimistic analysis by using data from the arm with larger effect size, and a conservative analysis by data from the arm with smaller effect size. For arm pain score, we also conducted a sensitivity analysis using the average pain score of both arms. Additional sensitivity analyses were conducted by excluding studies rated high risk of bias.

Statistical heterogeneity among the studies was assessed using Cochran’s χ2 test and the I2 statistic.6 For analyses with at least 10 trials, we constructed funnel plots and performed the Egger test to detect small sample effects (a marker for potential publication bias).7 All meta-analyses were conducted using Stata/SE 16.1 (StataCorp, College Station, TX).

To help determine the degree of effect, we examined the magnitude of relative risks and mean differences according to Table A-3. There were instances where a statistically significant difference between treatments was of such a small magnitude as to not be clinically meaningful. Conversely, there were instances where a small, moderate, or large effect was found but was not statistically significant.

2.1.5. Grading the Strength of the Body of Evidence

The EPC strength of evidence (SOE) rating for each body of evidence was assessed as high, moderate, low, or insufficient, using the approach described in the AHRQ Methods Guide,2 based on study limitations, consistency, directness, precision, and reporting bias. These criteria were applied regardless of whether evidence was synthesized quantitatively or qualitatively. The I2 statistic was used to help assess consistency in pooled analyses; The confidence intervals surrounding effect estimates were reviewed for clear benefit, no effect, and clear harms to aid in assessing precision. We considered evidence from both randomized trials and nonrandomized studies in determining strength of evidence with greater weight given to randomized studies. Strength of evidence ratings reflected our confidence or certainty in the findings (Appendix G1.1). Strength of evidence was considered insufficient when evidence was sparse, of poor quality or too conflicting such that we were unable to draw conclusions. SOE was initially assessed by one researcher and confirmed by a second. Descriptions of criteria and overall grades are described in Table A-4 and Appendix G.

Table A-4Strength of evidence grades and definitions

GradeDefinition
High We are very confident that the estimate of effect lies close to the true effect for this outcome. The body of evidence has few or no deficiencies. We believe that the findings are stable, i.e., another study would not change the conclusions.
Moderate We are moderately confident that the estimate of effect lies close to the true effect for this outcome. The body of evidence has some deficiencies. We believe that the findings are likely to be stable, but some doubt remains.
Low We have limited confidence that the estimate of effect lies close to the true effect for this outcome. The body of evidence has major or numerous deficiencies (or both). We believe that additional evidence is needed before concluding either that the findings are stable or that the estimate of effect is close to the true effect.
Insufficient We have no evidence, we are unable to estimate an effect, or we have no confidence in the estimate of effect for this outcome. No evidence is available or the body of evidence has unacceptable deficiencies, precluding reaching a conclusion.

Table A-4 taken from page 18 of the AHRQ Methods Guide.2

2.1.6. Peer Review and Public Commentary

An associate editor from a different EPC reviewed the draft report. Experts were invited to provide external peer review of this systematic review; AHRQ also provided comments. In addition, the draft report was posted on the AHRQ website June 9 to July 7, 2023, for public comment. All comments were reviewed and used to inform revisions to the draft report.

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