Aïda Bafeta, PhD; Mitsuki Koh, MPH; Carolina Riveros, MSc; Philippe Ravaud, MD, PhD
Note: All authors, external and internal, had full access to all the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Acknowledgment: The authors thank Elise Diard (French Cochrane Center) for help with the figures and Laura Smales (BioMedEditing, Toronto, Ontario, Canada) and Caroline Barnes for language revision of the manuscript. The authors are particularly indebted to Lina Ghosn El Chall for data extraction.
Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-0343.
Reproducible Research Statement:Study protocol: Available at www.clinicalepidemio.fr/protocols/. Statistical code: Not applicable. Data set: See tables, figures, and Appendix materials for all relevant data. For more details, contact Dr. Bafeta (e-mail, firstname.lastname@example.org).
Corresponding Author: Aïda Bafeta, PhD, Centre d'Epidémiologie Clinique, INSERM U1153, Hôpital Hôtel-Dieu, 1 place du Parvis Notre Dame, 75004 Paris, France; e-mail, email@example.com.
Current Author Addresses: Dr. Bafeta, Ms. Koh, Ms. Riveros, and Pr. Ravaud: Centre d'Epidémiologie Clinique, INSERM U1153, Hôpital Hôtel-Dieu, 1 place du Parvis Notre Dame, 75004 Paris, France.
Author Contributions: Conception and design: A. Bafeta, M. Koh, P. Ravaud.
Analysis and interpretation of the data: A. Bafeta, M. Koh, P. Ravaud.
Drafting of the article: A. Bafeta, P. Ravaud.
Critical revision for important intellectual content: A. Bafeta, P. Ravaud.
Final approval of the article. A. Bafeta, M. Koh, C. Riveros, P. Ravaud.
Obtaining of funding: P. Ravaud.
Administrative, technical, or logistic support: M. Koh, P. Ravaud.
Collection and assembly of data: A. Bafeta, M. Koh, C. Riveros, P. Ravaud.
Probiotics, prebiotics, and synbiotics are used increasingly, although the safety and potential harms of these interventions are poorly understood.
To examine how harms-related information is reported in publications of randomized controlled trials (RCTs) of probiotics, prebiotics, and synbiotics.
Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science (without language restrictions) from 1 January 2015 to 20 March 2018.
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.
4 reviewers independently assessed study characteristics, the reporting of harms, and the presentation of safety results.
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 high-risk 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.
Journal publication processes may have affected the completeness of reporting; only English-language publications were examined.
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.
No specific funding.
Bafeta A, Koh M, Riveros C, Ravaud P. Harms Reporting in Randomized Controlled Trials of Interventions Aimed at Modifying Microbiota: A Systematic Review. Ann Intern Med. [Epub ahead of print 17 July 2018]169:240–247. doi: 10.7326/M18-0343
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Published: Ann Intern Med. 2018;169(4):240-247.
Published at www.annals.org on 17 July 2018
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