Kate Snedeker

A systematic review of vaccinations to reduce the shedding of Escherichia coli O157 in the faeces of domestic ruminants.

The objective of this study was to conduct a systematic review and meta‐analysis of the published literature to evaluate the efficacy of vaccines in reducing faecal shedding of Escherichia coli O157 in ruminants. A systematic search of eight databases and land‐grant university research reports using an algorithm adapted from a previous systematic review of pre‐harvest interventions against E. coli O157 was conducted to locate all reports of in vivo trials of E. coli O157 vaccines in ruminants published between 1990 and 2010. All located references were screened by two independent reviewers, and data were extracted from all relevant papers, with treatment effect measured in odds ratios. For trials with a faecal prevalence outcome that did not involve mixing of treated and untreated cattle in the same pen, efficacy was explored using random‐effects meta‐analysis. Funnel plots were used to evaluate publication bias, and random‐effects meta‐regression was performed to explore heterogeneity. The search located 20 relevant manuscripts which detailed 24 trials and 46 treatment comparisons; all but one trial involved cattle. There were 9 deliberate challenge trials (19 comparisons), and 15 natural exposure trials (27 comparisons). For Type III protein vaccines, there were 9 natural exposure trials detailing 17 comparisons, and meta‐analysis of 8 comparisons revealed that vaccine treatment resulted in a statistically significant reduction in E. coli O157 faecal prevalence [odds ratio (OR) = 0.38, 95% confidence interval (CI) = 0.29, 0.51]. Siderophore receptor and porin protein (SRP) vaccines (three trials/four comparisons) also reduced faecal prevalence (OR = 0.42, 95% CI = 0.20, 0.61); however, none of the bacterin vaccine trials (n = 3, six comparisons) resulted in a statistically significant reduction in prevalence. The results suggest that Type III protein and SRP vaccines significantly reduce faecal shedding in cattle; however, caution should be taken in interpreting the results because of the heterogeneity in the results.

Methodological quality and completeness of reporting in clinical trials conducted in livestock species

Randomized controlled trials (RCTs) are the gold standard for evaluating efficacy of treatments under real world conditions and, as such, it is important that they are conducted with methodological rigour to prevent biased results. Many medical journals have adopted a standard checklist for reporting of RCTs, the CONSORT statement. The objective of this study was to evaluate clinical trials in livestock populations to assess methodological quality and completeness of reporting and to investigate the association between these criteria and treatment effects. A total of 100 clinical trials published between 2006 and 2008 in the English language were randomly selected. For each trial, 2 reviewers independently completed a checklist based on the CONSORT statement and a different 2 reviewers completed a standard template describing the outcomes used and the statistical significance of all reported treatment effects. Disagreements among reviewers were resolved by consensus. The results showed that there were substantive deficiencies in the reporting of many of trial features, both related to methodological quality and completeness of reporting. Details on key features such as randomization, double blinding, and the number of subjects lost to follow-up were reported in only 67, 4, and 62% of trials, respectively. Reporting of random allocation to treatment group was associated with a lower proportion of positive treatments effects within trials, as was reporting of inclusion/exclusion criteria for study subjects, details on the intervention, animal signalment, significance tests of baseline differences for at least one variable, and the methods used to measure all outcomes. The results suggest that there are deficiencies in the current reporting of important features of RCTs conducted in livestock species and that these deficiencies may be associated with biased treatment effects. The creation and adoption of standards for trial reporting in livestock could aid authors, reviewers, and editors in ensuring that necessary trial details are reported in all published trials.

The REFLECT Statement: Reporting Guidelines for Randomized Controlled Trials in Livestock and Food Safety: Explanation and Elaboration

Concerns about the completeness and accuracy of reporting of randomized clinical trials (RCTs) and the impact of poor reporting on decision making have been documented in the medical field over the past several decades. Experience from RCTs in human medicine would suggest that failure to report critical trial features can be associated with biased estimated effect measures, and there is evidence to suggest that similar biases occur in RCTs conducted in livestock populations. In response to these concerns, standardized guidelines for reporting RCTs were developed and implemented in human medicine. The Consolidated Standards of Reporting Trials (CONSORT) statement was first published in 1996, with a revised edition published in 2001. The CONSORT statement consists of a 22‐item checklist for reporting a RCT and a flow diagram to follow the number of participants at each stage of a trial. An explanation and elaboration document not only defines and discusses the importance of each of the items, but also provides examples of how this information could be supplied in a publication. Differences between human and livestock populations necessitate modifications to the CONSORT statement to maximize its usefulness for RCTs involving livestock. These have been addressed in an extension of the CONSORT statement titled the REFLECT statement: Methods and processes of creating reporting guidelines for randomized control trials for livestock and food safety. The modifications made for livestock trials specifically addressed the common use of group housing and group allocation to intervention in livestock studies; the use of deliberate challenge models in some trials and the common use of non‐clinical outcomes, such as contamination with a foodborne pathogen. In addition, the REFLECT statement for RCTs in livestock populations proposed specific terms or further clarified terms as they pertained to livestock studies.

Quality of Reporting of Clinical Trials of Dogs and Cats and Associations with Treatment Effects

BACKGROUND To address concerns about the quality of reporting of randomized controlled trials, and the potential for biased treatment effects in poorly reported trials, medical journals have adopted a common set of reporting guidelines, the Consolidated Standards of Reporting Trials (CONSORT) statement, to improve the reporting of randomized controlled trials. HYPOTHESIS The reporting of clinical trials involving dogs and cats might not be ideal, and this might be associated with biased treatment effects. ANIMALS Dogs and cats used in 100 randomly selected reports of clinical trials. METHODS Data related to methodological quality and completeness of reporting were extracted from each trial. Associations between reporting of trial features and the proportion of positive treatment effects within trials were evaluated by generalized linear models. RESULTS There were substantive deficiencies in reporting of key trial features. An increased proportion of positive treatment effects within a trial was associated with not reporting: the method used to generate the random allocation sequence (P < .001), the use of double blinding (P < .001), the inclusion criteria for study subjects (P = .003), baseline differences between treatment groups (P = .006), the measurement used for all outcomes (P = .002), and possible study limitations (P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE Many clinical trials involving dogs and cats in the literature do not report details related to methodological quality and aspects necessary to evaluate external validity. There is some evidence that these deficiencies are associated with treatment effects. There is a need to improve reporting of clinical trials, and guidelines, such as the CONSORT statement, can provide a valuable tool for meeting this need.

The REFLECT Statement: Methods and Processes of Creating Reporting Guidelines for Randomized Controlled Trials for Livestock and Food Safety by Modifying the CONSORT Statement

The conduct of randomized controlled trials in livestock with production, health and food‐safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A 2‐day consensus meeting was held on 18–19 November 2008 in Chicago, IL, USA, to achieve the objective. Prior to the meeting, a Web‐based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food‐safety researchers, livestock‐production specialists, journal editors, assistant editors and associate editors. Prior to the meeting, the attendees completed a Web‐based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety and 22‐item checklist. Fourteen items were modified from the CONSORT checklist and an additional sub‐item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health and food‐safety outcomes.

Quality of reporting in clinical trials of preharvest food safety interventions and associations with treatment effect.

Randomized controlled trials (RCTs) are the gold standard for evaluating treatment efficacy. Therefore, it is important that RCTs are conducted with methodological rigor to prevent biased results and report results in a manner that allows the reader to evaluate internal and external validity. Most human health journals now require manuscripts to meet the Consolidated Standards of Reporting Trials (CONSORT) criteria for reporting of RCTs. Our objective was to evaluate preharvest food safety trials using a modification of the CONSORT criteria to assess methodological quality and completeness of reporting, and to investigate associations between reporting and treatment effects. One hundred randomly selected trials were evaluated using a modified CONSORT statement. The majority of the selected trials (84%) used a deliberate disease challenge, with the remainder representing natural pathogen exposure. There were widespread deficiencies in the reporting of many trial features. Randomization, double blinding, and the number of subjects lost to follow-up were reported in only 46%, 0%, and 43% of trials, respectively. The inclusion criteria for study subjects were only described in 16% of trials, and the number of animals housed together was only stated in 52% of the trials. Although 91 trials had more than one outcome, no trials specified the primary outcome of interest. There were significant bivariable associations between the proportion of positive treatment effects and failure to report the number of subjects lost to follow-up, the number of animals housed together in a group, the level of treatment allocation, and possible study limitations. The results suggest that there are substantive deficiencies in reporting of preharvest food safety trials, and that these deficiencies may be associated with biased treatment effects. The creation and adoption of standards for reporting in preharvest food safety trials will help to ensure the inclusion of important trial details in all publications.

Analysis of trends in the full publication of papers from conference abstracts involving pre-harvest or abattoir-level interventions against foodborne pathogens

Study results are often presented as abstracts at scientific conferences before publication as full articles in peer-reviewed journals. Given the current emphasis on evidence-based decision-making, it is vital that the peer-reviewed literature represents as broad and un-biased a selection of studies as possible. While the proportion of abstracts published as full papers in the peer-reviewed literature has been extensively studied in human healthcare, no such studies have been published in the field of food safety. The goal of this study was to estimate the proportion published and average time to publication for conference abstracts involving studies of pre-harvest or abattoir interventions to reduce foodborne pathogens. Abstracts were obtained by hand-searching available proceedings between 1995 and 2004 from 10 conferences. Included abstracts were limited to those detailing non-observational, controlled in vivo trials where outcome(s) were measured in livestock, carcasses or eggs. Data on abstract type (<or=500 words, >500 words), species, intervention, study type, sample size, number housed together and outcomes were recorded. Four databases (Agricola, CAB, Web of Science, Scholars Portal) were searched for published papers corresponding to the conference abstracts using author and intervention/pathogen terms. Time to publication and overall median time to publication were estimated. Chi-squared, logistic regression and survival analyses were used to test for significant differences in proportion published and time to publication between variable levels. Of the 149 abstracts identified, 68 (45.6%) were published in peer-reviewed journals within 4 years. The median time to publication was 13.5 months (range: 0, 72). Abstracts shorter than 1 page were significantly more likely to be published (OR=2.2, 95% CI=1.0, 4.8), and abstracts involving pork or pigs were significantly less likely to be published that those involving poultry (OR=0.4: 0.2, 0.8). Abstracts reporting at least one positive outcome were more likely to be published (OR=2.608: 1.097, 6.196) and were published faster (HR=2.3: 1.1, 4.7). Time to publication decreased with the number of positive outcomes reported (HR=1.1: 1.0, 1.3). Sample size could only be determined for 46% of abstracts, with a median sample size of 9 (range 1-378), and housing was sufficiently described to determine sample size in 35% of pre-slaughter studies. The potential effects of this bias on systematic reviews and uses of interventions could be significant, and thus improvements may be warranted in the proportion of conference abstracts resulting in papers in the peer-reviewed literature.

Comparison of outcomes and other variables between conference abstracts and subsequent peer-reviewed papers involving pre-harvest or abattoir-level interventions against foodborne pathogens.

Accuracy in the reporting of studies in conference abstracts is important because the majority of studies in such abstracts are never further detailed in peer-reviewed publications, and data from such abstracts may be used in systematic reviews. Previous research on interventional studies in human biomedicine indicates that there is no guarantee of consistency between a conference abstract and paper in the reporting of results and other key variables. However, no research has been done to determine if this lack of reporting consistency in abstracts and papers extends to interventional studies in pre-harvest/harvest-level food safety. The goal of this study was to compare outcome results and other key variables between conference abstracts and subsequent peer-reviewed publications describing studies of pre-harvest and abattoir-level interventions against foodborne pathogens, and to determine whether the agreement in the results or key variables was associated with the time to full publication. A systematic search identified 59 conference abstracts with matching peer-reviewed papers (matches), and data on variables including outcome measures and results, pathogens, species, interventions, overall efficacy of intervention, sample size and housing were extracted from both the conference abstracts and the papers. The matching of variables between abstracts and papers was described, and logistic regression used to test for associations between variable matching and time to publication. Sample size was only provided for both abstract and paper in 24 matches; the same sample size was reported in 20 of these matches. Most other variables were reported in the majority of abstracts/papers, and with the exception of outcomes and intervention effect, the reporting of variables was relatively consistent. There was no significant difference in the numbers of authors, with the first author the same in 78.3% of matches. Of 231 outcome measures reported in both abstracts and papers, nearly one third (77% or 32.2%) had different results, with 32 changing direction of effect. More than a quarter of matches involved at least one significant change in outcome result. The overall conclusion on the efficacy of the intervention changed in 10.7% of matches. There was a significant association between increased time to publication and differences in the number of authors, and having fewer outcome measures in the abstract reported in the paper. These results suggest that data from conference abstracts should be considered with caution.

Completeness of reporting in abstracts from clinical trials of pre-harvest interventions against foodborne pathogens

Abstracts are the most commonly read part of a journal article, and play an important role as summaries of the articles, and search and screening tools. However, research on abstracts in human biomedicine has shown that abstracts often do not report key methodological features and results. Little research has been done to examine reporting of such features in abstracts from papers detailing pre-harvest food safety trials. Thus, the objective of this study was to assess the quality of reporting of key factors in abstracts detailing trials of pre-harvest food safety interventions. A systematic search algorithm was used to identify all in vivo trials of pre-harvest interventions against foodborne pathogens in PubMed and CAB Direct published from 1999 to October 2009. References were screened for relevance, and 150 were randomly chosen for inclusion in the study. A checklist based on the CONSORT abstract extension and the REFLECT Statement was used to assess the reporting of methodological features and results. All screening and assessment was performed by two independent reviewers with disagreements resolved by consensus. The systematic search returned 3554 unique citations; 356 were found to be relevant and 150 were randomly selected for inclusion. The abstracts were from 51 different journals, and 13 out of 150 were structured. Of the 124 abstracts that reported whether the trial design was deliberate disease challenge or natural exposure, 113 were deliberate challenge and 11 natural exposure. 103 abstracts detailed studies involving poultry, 20 cattle and 15 swine. Most abstracts reported the production stage of the animals (135/150), a hypothesis or objective (123/150), and results for all treatment groups (136/150). However, few abstracts reported on how animals were grouped in housing (25/150), the location of the study (5/150), the primary outcome (2/126), level of treatment allocation (15/150), sample size (63/150) or whether study units were lost to follow up (4/150). Forty-eight (48/150) abstracts reported the name, mode of administration, dose and duration of the intervention(s), while 102 (102/150) reported at least one of these elements. Nine (9/150) abstracts specified that allocation of study units to treatments was randomized, and none of the abstracts reported whether blinding was used (0/150). These results reveal gaps in reporting of methodological features and results. Thus, improving reporting quality in abstracts should be a crucial goal to be pursued by authors, reviewers and journal editors.