Kotowska 2005.

Methods	Placebo controlled RCT, follow‐up: 2 weeks after last study drug dose
Participants	Pediatric population, mixed inpatient and outpatient, Poland, unclear if patients with recurrent C. difficile were included
Interventions	S. boulardii 10 x 109 cfu/day or placebo for duration of antibiotic course
Outcomes	CDAD, AAD and AE
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“Investigators at the Medical University of Warsaw used computers to generate independent allocation sequences and randomization lists for each study site. To avoid a disproportionate number of patients in the experimental or placebo group, randomization at each site was performed in blocks of six (three received placebo and three, active treatment)”
Allocation concealment (selection bias)	Low risk	“To ensure allocation concealment, an independent subject prepared the randomization schedule and oversaw the packaging and labelling of trial treatments”
Blinding of participants and personnel (performance bias) CDAD	Low risk	“All investigators, participants, outcome assessors and data analysts were blinded to the assigned treatment throughout the study” “The active treatment and placebo used in this study were prepared centrally by the hospital pharmacy at the Medical University of Warsaw as identically appearing wafers”
Blinding of participants and personnel (performance bias) AE	Low risk	See above: Blinding of participants and personnel (performance bias) CDAD
Blinding of participants and personnel (performance bias) AAD	Low risk	See above: Blinding of participants and personnel (performance bias) CDAD
Blinding of outcome assessment (detection bias) CDAD	Low risk	Outcome assessors were blinded
Blinding of outcome assessment (detection bias) AE	Low risk	Blinding of outcome assessment (detection bias) CDAD
Blinding of outcome assessment (detection bias) AAD	Low risk	Blinding of outcome assessment (detection bias) CDAD
Incomplete outcome data (attrition bias) CDAD	Low risk	“Overall, 23 (8.6%) of the randomized children [13 (9.8%) in the S. boulardii group and 10 (7.2%) in the placebo group] withdrew before completing the trial and were lost to follow‐up. The reasons for not completing the trial were non‐acceptance of the allocated intervention (n = 22) or damage of the study product (n = 1)”   A relatively low number of participants had missing data post randomization. The missing data was balanced between groups both in number and reasons given for the missing outcome data. Additionally, an extreme case scenario regarding the missing data was calculated by the authors and shown to not influence the authors’ conclusions. While it is unclear from the paper if this extreme case scenario was conducted for outcomes besides AAD (the authors’ primary outcome), we consider the missing data to not realistically have a risk of ‘material’ bias on the authors’ conclusions regarding CDAD
Incomplete outcome data (attrition bias) AE	Low risk	There were no AE reported in either group. Although an extreme disproportion in AE event rates in the missing outcome data could have affected the estimate of AE it seems highly unlikely based on the rationale given for the missing data, null event rate in both groups, as well as the overall low amount of missing data
Incomplete outcome data (attrition bias) AAD	Low risk	See above; Incomplete outcome data (attrition bias) CDAD
Selective reporting (reporting bias)	Low risk	A protocol of this trial was not located. All outcomes listed in ‘methods’ were analysed in ‘results.’ We consider the risk of reporting bias to be low
Other bias	Unclear risk	Baseline participant characteristics roughly equivalent with no significant differences noted. No financial support, funding, or conflict of interest were listed. According to our a priori criteria for risk of funding bias we consider the risk of bias here to be unclear