Target trial emulation: Do antimicrobials or gastrointestinal nutraceuticals prescribed at first presentation for acute diarrhoea cause a better clinical outcome in dogs under primary veterinary care in the UK?

Abstract

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. Veterinary electronic clinical records represent a potentially valuable source of information to estimate real-world causal effects for companion animal species. This study employed the target trial framework to evaluate the usefulness on veterinary observational data. Acute diarrhoea in dogs was used as a clinical exemplar. Inclusion required dogs aged ≥ 3 months and < 10 years, presenting for veterinary primary care with acute diarrhoea during 2019. Treatment strategies were: 1. antimicrobial prescription compared to no antimicrobial prescription and 2. gastrointestinal nutraceutical prescription compared to no gastrointestinal nutraceutical prescription. The primary outcome was clinical resolution (defined as no revisit with ongoing diarrhoea within 30 days from the date of first presentation). Informed from a directed acyclic graph, data on the following covariates were collected: age, breed, bodyweight, insurance status, comorbidities, vomiting, reduced appetite, haematochezia, pyrexia, duration, additional treatment prescription and veterinary group. Inverse probability of treatment weighting was used to balance covariates between the treatment groups for each of the two target trials. The risk difference (RD) of 0.4% (95% CI -4.5% to 5.3%) was non-significant for clinical resolution in dogs treated with antimicrobials compared with dogs not treated with antimicrobials. The risk difference (RD) of 0.3% (95% CI -4.5% to 5.0%) was non-significant for clinical resolution in dogs treated with gastrointestinal nutraceuticals compared with dogs not treated with gastrointestinal nutraceuticals. This study successfully applied the target trial framework to veterinary observational data. The findings show that antimicrobial or gastrointestinal prescription at first presentation of acute diarrhoea in dogs causes no difference in clinical resolution. The findings support the recommendation for veterinary professionals to limit antimicrobial use for acute diarrhoea in dogs.

Later-age neutering causes lower risk of early‐onset urinary incontinence than early neutering–a VetCompass target trial emulation study

“…The study design applied the target trial emulation method [ 25 ], similar to a previous studiesbased on primary-care EHR data [ 27 , 28 ]. Because manual extraction of data from EHRs is time intensive, the case-control design allowed for confounders to be extracted for a requisite subset of cases and controls.…”

“…Thus within the target trial framework, an observational study is considered as a conditionally randomised experiment, taking in to account the measured covariates [ 26 , 27 ]. Successful application of this approach within the veterinary literature has recently been demonstrated, with studies using primary-care EHR data evaluating: 1) whether antimicrobial or gastrointestinal nutraceutical treatment in acute, uncomplicated canine diarrhoea causes improved clinical outcomes [ 28 ] and 2) whether surgical or non-surgical management for cranial cruciate ligament rupture in dogs causes improved clinical outcomes [ 27 ].…”

“…Additionally, previous studies that attempted to explore the effects of age at neutering on UI diagnosis were limited to reporting associations rather than causal effects [ 3 , 12 , 15 , 17 – 19 ]. Therefore, a fuller evaluation of the causal role of age at neutering in the development of UI is warranted, with recent advances in causal inference methodology now enabling research to progress from studying association to reporting causation [ 27 , 28 ].…”

“…It was hypothesized that neutering at ≥ 7 to ≤ 18 months causes a decreased odds of early-onset UI diagnosis compared with neutering at 3 to < 7 months [ 3 , 18 , 19 ]. Target trial emulation and causal inference analyses were adopted to attenuate as many sources of bias as possible from the use of observational data in the study [ 25 , 27 , 28 ].…”

The Function of Probiotics and Prebiotics on Canine Intestinal Health and Their Evaluation Criteria

“…Previous studies showed that probiotic and prebiotic products can significantly improve the clinical condition, indicating these products had potential treatment effects [ 82 , 84 ]. However, recent reports indicate that the use of probiotic products is not clinically significant for preventing or treating acute diarrhea in dogs [ 85 , 86 ]. The conclusions are controversial due to the lack of uniform evaluation criteria for all the study cases compared to their reports.…”