Dr. Laura Selmic part of collaborative effort to improve clinical trial reporting for dogs and cats
Article by: Allison Burk
Originally Published
Dr. Laura E. Selmic, associate professor of veterinary clinical sciences and Teckie and Don Shackelford Chair in Canine Medicine at Ohio State’s College of Veterinary Medicine, recently contributed to efforts to standardize reporting guidelines for randomized controlled clinical trials involving dogs and cats.
Dr. Annette O’Connor, chair of the MSU College of Veterinary Medicine’s Department of Large Animal Clinical Sciences and professor of epidemiology and Dr. Jan Sargeant, emeritus professor at the University of Guelph (Ontario, Canada), joined Selmic on a steering committee led by Dr. Audrey Ruple, Dorothy A. and Richard G. Metcalf professor of veterinary medical informatics and associate professor of quantitative epidemiology at Virginia Tech’s Virginia-Maryland College of Veterinary Medicine, to develop the new PetSORT guidelines. The guidelines, as well as their methods and development process, were published in the journal Frontiers in Veterinary Medicine.
According to Ruple, she and her steering committee collaborators went through a year of published results from randomized controlled clinical trials conducted in dogs and cats and found, in general, “they weren't reported well, meaning that in the majority of cases they weren't reported completely, and key methodological features were often missing, which makes it difficult to interpret trial results.” That led to the effort to standardize reporting guidelines for those clinical trials.
“The point of it is to ensure that we are doing a good job of reporting, especially because when we think about meta-analyses, which is where we combine results of multiple randomized controlled trials, if the initial trials are not reported well, we can’t synthesize their results,” Ruple said. “And so then it becomes a research wastage issue.”
Selmic is a small animal surgical oncologist at Ohio State and works with clinical trials daily. She emphasized that clinical trial reporting guidelines are so impactful for the small animal veterinary community at large.
“Clinical trials need to be reported in a standardized way so clinicians and scientists can glean the most complete information from these studies and so that in the future these guidelines can be used in other studies like systematic reviews and metanalyses,” Selmic said.
Now that these guidelines are published, the next step for this group of veterinary epidemiologists is getting journal editors and private and public labs across North America to begin utilizing them to affect the quality of reporting.
Ruple said they now have a whole battery of checklists for research conducted using large animals and companion animals, and they plan to send them out to all the academic research teams across the U.S., Canada, Australia, and the U.K. Adding that the outreach will include deans of research so they will be more aware of the checklists and guidelines, and hopefully will, in turn, pass that on to their faculty.
The PetSORT collaborators have a group of 56 experts from academia and the public and private sectors as their consensus panel. They hope they will serve as advocates for the guidelines in the respective areas, including veterinary clinics and, ultimately, pet owners.
“Of course, improved reporting of trial results also directly impacts the wellbeing of pets, and even benefits clinicians’ wellbeing by reducing uncertainty in clinical decision making,” said Michigan State’s O’Connor.
Guidelines from research in human populations were modified for dogs and cats to create the PetSORT checklist, which can be viewed below.
PETSORT CHECKLIST
Title and Abstract
1a. Identify the study as a randomized trial in the title.
1b. Summarize the objective, trial design, primary outcome(s), study population, intervention, results, and conclusions/clinical relevance.
Introduction: Background and Objectives
2a. Give scientific background and explanation of rationale.
2b. Specify objectives or hypotheses.
Methods: Trial Design
3a. Describe trial design (such as parallel, factorial, crossover) and the intervention allocation level (such as animal, litter, kennel). For crossover trials, description of the number and duration of intervention and washout periods.
3b. Report any changes to methods after trial commencement (such as eligibility criteria), with reasons.
Methods: Participants
4a. Report eligibility criteria for animals and their caregivers (including owners of pets and custodians of shelter animals) at all organizational levels (such as animals or veterinary clinics). State whether animals were shelter-owned or client-owned.
4b. Describe the settings and locations where the data were collected. Describe sources of clustering (such as multiple veterinary practices or group housing).
Methods: Interventions
5. Describe interventions for each group with sufficient details to allow replication. Describe the unit of allocation (such as body part (eye), individual animal, litter).
Methods: Outcomes
6a. Completely define pre-specified primary and secondary outcome measures, including how, when, and by whom they were assessed.
6b. Describe any changes to trial outcomes after the trial commenced, with reasons.
6c. If the outcome of interest (such as survival time) could be differentially impacted by euthanasia, describe methods used to reduce bias in study results (such as standardized criteria or counseling for euthanasia).
Methods: Sample Size
7a. Provide a sample size calculation or a justification for the sample size if a calculation was not performed.
7b. When applicable, explain any interim analyses and stopping guidelines.
Methods: Randomization: Sequence Generation
8a. Describe the method used to generate the random allocation sequence.
8b. Describe the type of randomization and include details of any restriction (such as stratification, blocking, and block size) used.
Methods: Allocation Concealment
9. Describe the steps taken to conceal the allocation sequence until interventions were assigned.
Methods: Implementation
10. Describe who generated the random allocation sequence, who enrolled study subjects, and who assigned them to interventions.
Methods: Blinding or Masking
11a. Report which individuals (such as caregivers, investigators, outcome assessors, data analysts) were blinded/masked after allocation. Provide justification if not blinded/masked.
11b. If relevant, describe the similarity of interventions.
Methods: Statistical Methods
12a. Describe the statistical methods used to compare groups for primary and secondary outcomes.
12b. Describe the methods used for ancillary analyses, such as subgroup analyses and adjusted analyses; report if these were pre-specified in the protocol or unplanned.
Results: Study Subject Flow
13a. For each group, state the number of study units (body part, individual animal, or litter) assessed for eligibility, randomly assigned, received the intended intervention, and analyzed for each primary and secondary outcome.
13b. Quantify and explain any losses and exclusions after randomization for each group (such as the number per group removed due to adverse events) and for each intervention period in a crossover trial.
Results: Recruitment
14a. Report the dates defining the periods of recruitment and follow-up.
14b. If the trial was discontinued early, provide the reason.
Results: Baseline Data
15. Provide a detailed description (such as a table) of baseline demographic and clinical characteristics that could impact the outcomes for each intervention group.
Results: Numbers Analyzed
16. Report the number analyzed for the primary and all secondary outcomes and whether the analysis was by original assigned groups (intervention-to-treat) or per protocol. Explicitly report the number of units lost to follow-up and, if relevant, the number of animals with changed intervention assignments (if relevant per protocol).
Results: Outcomes and Estimation
17a. For each primary and secondary outcome, report the results for each group, and the estimated effect size and its precision (such as 95% confidence interval).
17b. For binary outcomes, present both absolute and relative effect sizes.
Results: Ancillary Analyses
18. Present the results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from unplanned or exploratory analyses.
Results: Harms
19. Describe the methods for the detection of adverse events and report all adverse events (expected, unexpected, and suspected) or unintended effects observed in each group or their absence.
Discussion: Interpretation
20. Ensure that interpretation is consistent with results, balancing benefits and harms, and considering other relevant evidence.
Discussion: Generalizability
21. Discuss generalizability (external validity, applicability) of the trial findings.
Discussion: Limitations
22. Discuss trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses. Consider potential carryover effects if a crossover trial.
Other Information: Registration
23. State whether the trial was registered and, if so, provide a registration number and name of trial registry. If not, provide a reason for not registering the trial in advance.
Other Information: Protocol
24. State if the full trial protocol was finalized a priori and where it can be accessed. Describe any protocol deviations with justification.
Other Information: Funding and Transparency
25. State sources of funding and other support (such as supply of drugs), role of funders, conflict of interest, ethical approval for human (if applicable) and animal subject use, and quality standards used.