Target Trial Emulation: Does surgical versus non-surgical management of cranial cruciate ligament rupture in dogs cause different outcomes?

Camilla Pegram, Karla Diaz-Ordaz, Dave C Brodbelt, Yu-Mei Chang, Anna Frykfors von Hekkel, Chieh-Hsi Wu, David B Church, Dan G O'Neill
Prev Vet Med. 2024 Mar 4:226:106165. doi: 10.1016/j.prevetmed.2024.106165.

Target trial emulation applies design principles from randomised controlled trials to the analysis of observational data for causal inference and is increasingly used within human epidemiology. 

Using anonymised veterinary clinical data from the VetCompass Programme, this study applied the target trial emulation framework to determine whether surgical (compared to non-surgical) management for cranial cruciate ligament (CCL) rupture in dogs causes improved short- and long-term lameness and analgesia outcomes. 

The emulated target trial included dogs diagnosed with CCL rupture between January 1, 2019 and December 31, 2019 within the VetCompass database. Inclusion in the emulated trial required dogs aged ≥ 1.5 and < 12 years, first diagnosed with unilateral CCL rupture during 2019 and with no prior history of contralateral ligament rupture or stifle surgery. Dogs were retrospectively observed to have surgical or non-surgical management. Informed from a directed acyclic graph derived from expert opinion, data on the following variables were collected: age, breed, bodyweight, neuter status, insurance status, non-orthopaedic comorbidities, orthopaedic comorbidities and veterinary group. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding, with weights calculated based on a binary logistic regression exposure model. Censored dogs were accounted for in the IPTW analysis using inverse probability of censoring weighting (IPCW). The IPCWs were combined with IPTWs and used to weight each dog's contribution to binary logistic regression outcome models. 

Standardized mean differences (SMD) examined the balance of covariate distribution between treatment groups. The emulated trial included 615 surgical CCL rupture cases and 200 non-surgical cases. The risk difference for short-term lameness in surgically managed cases (compared with non-surgically managed cases) was -25.7% (95% confidence interval (CI) -36.7% to -15.9%) and the risk difference for long-term lameness -31.7% (95% CI -37.9% to -18.1%). 

The study demonstrated the application of the target trial framework to veterinary observational data. The findings show that surgical management causes a reduction in short- and long-term lameness compared with non-surgical management in dogs.