Integrating a randomized controlled trial with a parallel observational cohort study in cervical spine surgery insights from the foraminotomy ACDF cost-effectiveness trial (FACET).

Abstract

Background context: In most randomized controlled trials (RCT), data is primarily and often only available for individuals who have agreed to be randomized, with little, if any, consideration for those who elected not to participate.

Purpose: This study evaluated the value of including a concurrent observational cohort of patients who declined randomization in the Foraminotomy ACDF Cost-Effectiveness Trial (FACET-RCT) but still underwent anterior or posterior cervical surgery. The goal was to determine if the FACET-RCT results could be generalized by comparing baseline characteristics and clinical outcomes between the randomized trial and observational cohort.

Study design/setting: A nationwide RCT with a parallel observational cohort recruiting patients from routine care.

Patient sample: Between January 2016 and May 2020, 389 patients with cervical radiculopathy were screened, and 358 were eligible. Of these, 265 (74%) were randomized in the FACET-RCT for either posterior or anterior cervical surgery, while 80 (22%) opted out of randomization and were followed in an observational cohort. Only 13 (4%) patients declined participation in both FACET-RCT and cohort.

Outcome measures: Demographic data was collected, and primary outcomes included treatment success, evaluated using the Odom criteria as well as reduction in arm pain, assessed with a Visual Analogue Scale (VAS) at 6 weeks, and every 6 months up to 2 years postsurgery. Secondary outcomes included VAS for neck pain, neck disability, work ability, quality of life, treatment satisfaction, and need for revision surgeries.

Methods: Baseline characteristics were compared between the FACET-RCT and cohort using logistic regression. Primary and secondary outcomes were analyzed for differences between study designs using mixed-model analyses adjusted for confounders. The primary noninferiority endpoint of the FACET-RCT was evaluated in both the cohort and combined data from both cohort and FACET-RCT at 2 years of follow-up.

Results: Patients in the cohort were slightly younger than those in the FACET-RCT (mean age of 48.4 versus 51.2 years; mean difference [MD], -2.5; 95% confidence interval [CI], -4.8 to -0.2; p=.04). In sub-analyses stratified by surgical approach (anterior vs. posterior surgery), fewer patients in the observational cohort who underwent posterior surgery reported severe neck pain at baseline compared to their counterparts in the FACET-RCT (OR, 0.38; 95% CI: 0.14 to 0.92; p=.04). No other significant baseline differences were found. No significant differences in treatment success (OR, 1.3; 95% CI: 0.3 to 6.0; p=.75) and arm pain reduction (MD, -3.9; 95% CI: -9.2 to 1.5; p=.16) were observed between study designs. The primary noninferiority endpoint was achieved in the combined data from both the cohort and FACET-RCT, with a narrower CI compared to the FACET-RCT alone, indicating a more robust result. Secondary outcomes were comparable between groups.

Conclusions: Randomization did not influence clinical outcomes for cervical surgery patients. Combining RCT with the observational cohort increased statistical power, external validity and robustness. Our findings support the value of observational methods as a complement to RCTs, especially when a large number of patients refuse RCT participation and high dropout and crossover rates are expected.