Harms Reporting in Randomized Controlled Trials of Interventions Aimed at Modifying Microbiota A Systematic Review

Background: Probiotics, prebiotics, and synbiotics are used increasingly, although the safety and potential harms of these interventions are poorly understood. Purpose: To examine how harms-related information is reported in publications of randomized controlled trials (RCTs) of probiotics, prebiotics, and synbiotics. Data Sources: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science (without language restrictions) from 1 January 2015 to 20 March 2018. Study Selection: RCTs assessing the safety or efficacy of at least 1 intervention involving probiotics, prebiotics, or synbiotics alone or in combination with another intervention compared with any control (such as a placebo or an antibiotic) for any clinical condition. Data Extraction: 4 reviewers independently assessed study characteristics, the reporting of harms, and the presentation of safety results. Data Synthesis: Of 384 trials conducted in healthy volunteers (n = 136) or patients with any of several medical conditions (n = 248), 339 (88%) were published in specialty journals. Trials most often evaluated probiotics (n = 265 [69%]). Studies in persons with medical conditions enrolled outpatients (n = 195) and highrisk patients (n = 53). No harms-related data were reported for 106 trials (28%), safety results were not reported for 142 (37%), and the number of serious adverse events (SAEs) per study group was not given for 309 (80%). Of 242 studies mentioning harms-related results, 37% (n = 89) used only generic statements to describe AEs and 16% (n = 38) used inadequate metrics. Overall, 375 trials (98%) did not give a definition for AEs or SAEs, the number of participant withdrawals due to harms, or the number of AEs and SAEs per study group with denominators. Limitation: Journal publication processes may have affected the completeness of reporting; only English-language publications were examined. Conclusion: Harms reporting in published reports of RCTs assessing probiotics, prebiotics, and synbiotics often is lacking or inadequate. We cannot broadly conclude that these interventions are safe without reporting safety data.