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Analyzing Antimicrobials - Creating a New network of knowledge

Graphic illustration New research at the Ontario Veterinary College is tackling one of the biggest health challenges of the 20th century, the prudent and effective use of antimicrobials, and employing systematic reviews and network meta-analysis to search for answers to which treatment and management practices are most effective.

The study, conducted with support from The Pew Charita­ble Trusts, a non-profit research and public policy organization in the U.S., is focused on two areas: the efficacy of antibiotics used to prevent diseases in four livestock groups and the efficacy of non-antibiotic management practices used to try to prevent these diseases. 

This isn’t just a literature review, notes principal researcher Dr. Jan Sargeant, a professor and epidemiologist in the Ontario Veterinary College’s Department of Population Medicine, it’s a very detailed study using network meta-analysis. 

“This study fits beautifully into my interests in evidence synthesis, bringing together sci­entific information from a range of research sources to inform decisions on policies or clinical practice,” says Sargeant, “but it also taps into the broader OVC expertise and interest in prudent antimicrobial use and reducing antimicrobial resistance.” 

The first step in this work, creating protocols to describe the methods for each study, was completed in the summer and early fall of 2018. These eight time-stamped protocols, posted publically on a systematic review website (www.syreaf.org), outline exactly what the systematic review will involve: the rationale, objectives, and methods, including eligibility criteria and study designs. They outline information sources, search strategy, selection and data collection process, as well as outcomes, prioritization and how data synthesis will be completed. Any deviation from this will be recorded, ensuring transparency throughout the process, a critical piece of the systematic review method, notes Sargeant. 

“This is the international standard for systematic reviews, so it is very transparent,” she adds. “For each question, we then do a network meta-analysis.” 

Once reviewers enter data from relevant studies, the computer program literally draws a network using direct comparisons from the studies and then estimates indirect comparisons between them. 

“For example, there is more than one antibiotic choice to prevent specific infections. In a standard meta-analysis, we ask does antibiotic A work or does antibiotic B work? In a network meta-analysis, we look at relative efficacy.”

“If one study compares antibiotic A to antibiotic B and another compares antibiotic A to antibiotic C, the network can compare B to C based on the information it has,” says Sargeant. 

Ultimately, veterinarians want to know which treatment and which management practice works the best, she notes. Ideally this leads to more effective treatment decisions, as well as more prudent antibiotic use.

This is the next wave of where systematic reviews and evidence synthesis is going, she adds. 

Once the eight systematic reviews and network meta-analyses are complete, Sargeant will bring together a small group of epidemiologists and animal industry experts in early 2019 to discuss next steps. This will help to direct resources and identify research gaps. 

“We want to really drill down to identify where there are gaps and how we, as an agricultural community, who want to prudently use antibiotics, direct our research needs going forward,” she adds.

The science behind systematic reviews & network meta-analysis 

Imagine sifting through all the existing studies available to answer a specific question and synthesizing it to identify what has been dis­covered to date. That’s the essence of systematic reviews. 

An important part of evidence-based medicine, systematic reviews have been used for more than two decades in human health­care and are making important inroads into veterinary medicine. 

Systematic reviews are a type of literature review that uses a structured series of steps to critically appraise and synthesize research studies. They are designed to answer a specific clinical or policy question and to provide a transparent and comprehensive summary of current evidence relevant to a research question. Systematic reviews of clinical trials are vital to the practice of evidence-based medicine. Key to the success of systematic reviews in veterinary medicine has been the implementation of clearly defined reporting guidelines for clinical trials in animal health, animal production, welfare and food safety. 

Systematic reviews are an important tool to help veterinarians and animal health professionals understand the vast volume of scientific research available. For decision makers, they provide a transparent, comprehensive summary of current knowledge to incorporate scientific evidence into the decision-making process. They can also help recognize gaps in knowledge and provide insight when identifying questions that will need to be answered with future research. 

Using meta-analysis or network meta-analysis, researchers can combine results from multiple studies identified in a systematic review, looking for all the possible answers to a specific question. At OVC, recent work in this area includes identifying and analyzing studies that evaluate the efficacy of antibiotics for a particular health issue and using network meta-analysis, evaluate the comparative efficacy of different antibiotic treatments. 

Jan Sargeant has advanced reporting guidelines for observational (www.strobevet-statement.org) and clinical studies (www.REFLECT-statement.org) with animals, both developed in collaboration with Annette O’Connor, Iowa State University’s College of Veterinary Medicine.

Originally published in the Winter/Spring 2019 Crest Magazine.

(Illustration credit: istockphoto.com/CSA-Archive)