Breaking Barriers: Studying Fracture Healing in the BONES Program

The Bioventus Observational Noninterventional EXOGEN Studies (BONES) Program includes 3 concurrent studies designed to estimate the incidence of fracture nonunions in patients treated with the EXOGEN Ultrasound Bone Healing System compared with those receiving standard fracture care. This article outlines the design and methodology within the fifth metatarsal fracture study; similar approaches are taken in the second and third BONES Program studies, which examine nonunions of the tibia and scaphoid. The BONES Program is an external comparator design and incorporates several unique, fit-for-purpose components to strengthen the approach and allow it to be submitted to the US Food and Drug Administration (FDA) to be considered for a label expansion. BONES consisted of 2 cohorts: (1) EXOGEN-treated patients recruited into a patient registry and (2) comparator patients from a large administrative health claims database. The study used International Classification of Diseases, Tenth Revision, nonunion diagnosis codes reported by the treating clinician for the primary outcome measure. Many data sources (medical and billing records, patient-reported health data, usage data from the device itself, and commercial product complaint system) were used on the registry side, alongside insurance claims data to source the external comparator cohort, to achieve broader understanding of factors predisposing patients to the development of nonunions. In step with the FDA's increasing acceptance of real-world evidence for use in regulatory decision making and coupled with the infeasibility of a randomized clinical trial in this setting, the innovative study design of the BONES Program allowed for both an evaluation of the effect of EXOGEN in mitigating nonunions in a real-world setting and an assessment of the patient experience with EXOGEN treatment.