Research Trainee Mayo Clinic Rochester, Minnesota, United States
Introduction: Inclusivity and external validity of randomized controlled trials (RCTs) is often questioned. The aim of this study is to compare the demographics, baseline disease characteristics, and outcomes of RCTs to real-world data for FDA-approved cervical disk arthroplasty (CDA) devices.
Methods: We searched the PubMed, Embase, Cochrane, and Medline databases to identify studies on FDA-approved CDA devices, and we compared baseline and follow-up Neck Disability Index (NDI) between RCTs and observational studies. We also queried the ACS-NSQIP registry for elective CDA cases between 2005 and 2020, and compared demographics and indications for surgery between RCTs and the ACS-NSQIP registry.
Results: Our search identified 25 observational studies with 1,235 patients and 15 RCTs with 2,497 patients reporting surgical outcomes following CDA. Patients enrolled in RCTs had a higher baseline NDI score compared to observational studies (55.3 vs. 44.9; p< 0.01). The postoperative improvement in NDI was more prominent in RCTs compared to observational studies 12 and 24 months after surgery (28.4 vs. 36.9, p< 0.01; and 30.9 vs. 37.8, p=0.02). A total of 5,135 patients undergoing elective CDA were identified in the ACS-NSQIP registry. Compared to them, patients enrolled in RCTs had a lower mean age (44.5 vs. 46.3, p< 0.01), lower BMI (27.4 vs. 30.3, p< 0.01), and a higher proportion of white patients (83.3% vs. 75.5%, p< 0.01). Even though myelopathic patients have not been included in RCTs, myelopathy was the primary indication for surgery in 10% of cases in the ACS-NSQIP registry.
Conclusion : RCTs investigating the role of CDA in degenerative spine disease are more likely to enroll younger patients with lower BMI and of white race – an indirect indicator of socioeconomic status – who had a more severe disease-inflicted disability at baseline. Myelopathy – a relatively common indication for CDA in the real world – is not represented in an interventional trial setting. These discrepancies might contribute to the greater absolute benefit from surgery experienced by patients in RCTs compared to the real-world practice.
How to Improve Patient Care: The index analysis identifies factors that might limit the generalizability of evidence yielded from RCTs and underlines the importance of designing more inclusive and representative future RCTs.
