Psaradellis 2010.
| Methods | Placebo controlled RCT, follow‐up: 3 weeks after last study drug dose | |
| Participants | Adult population, mixed inpatient and outpatient, Canada, unclear if patients with recurrent C. difficile were included | |
| Interventions | Placebo orL. acidophilus CL1285 and L. casei 25 x 109 cfu/day for 2 days then 50 x 109 cfu/day until 5 days after discontinuation of antibiotic | |
| Outcomes | CDAD, AAD, and AE | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The method of randomization was not described |
| Allocation concealment (selection bias) | Unclear risk | Not enough information provided |
| Blinding of participants and personnel (performance bias) CDAD | Low risk | “This was a multicenter double‐blind, randomized, placebo controlled, study…” |
| 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 | There is no explicit mention of outcome assessor blinding. Outcomes of interest to our review from this trial include AE and CDAD. There is no mention of blinding of the cytotoxin assay personnel although this is a placebo controlled drug trial so we will consider the risk of bias to be low here |
| Blinding of outcome assessment (detection bias) AE | Low risk | “Safety was assessed by the incidence of treatment emergent adverse events, which were reported according to the MedDRA (version 10.1) dictionary of terms.” It appears AE were assessed by participants reporting to study personal all of whom were blinded and that an objective dictionary of terms was used for reported adverse events |
| Blinding of outcome assessment (detection bias) AAD | Low risk | Diarrhea assessed by blinded individuals |
| Incomplete outcome data (attrition bias) CDAD | High risk | “Among the 472 randomized patients, 29 patients were excluded from the ITT analysis due to antibiotic treatment duration of less than 3 days and 6 patients were excluded because diarrhea onset occurred before initiation of study treatment. Therefore a total of 437 (92.6%) were included in the ITT population…” “There were 16 patients in the BIO K+ group and 30 in the placebo group that underwent CDAD testing. Of these, 1 (6.2%) patient in the BIO K+ group and 4 (13.3%) in the placebo group were positive for the C. difficile toxins (odds ratio = 0.433, p = 0.645).” The missing data results from less than 10% of the participants and the numbers and reasons for those being excluded are balanced across groups. However, a 2:1 difference in sampling for CDAD is apparent and not representative of the difference in occurrence of AAD between groups. Therefore we must conclude a high risk of ‘material’ bias from incomplete and unbalanced outcome data for the CDAD outcome |
| Incomplete outcome data (attrition bias) AE | Low risk | The missing data results from less than 10% of the participants and the numbers and reasons for those being excluded are balanced across groups. Therefore we are not concerned about attrition bias as it relates to the AE outcomes |
| Incomplete outcome data (attrition bias) AAD | Low risk | See above: Incomplete outcome data (attrition bias) AE |
| Selective reporting (reporting bias) | Low risk | While not reported in the full text article a protocol was discovered on clinicaltrials.gov. The primary outcome listed in the protocol was reported on in the paper. However a secondary outcome listed in the protocol was not mentioned in the paper: “Health outcome evaluation will look at the direct medical costs and clinical outcomes of alternative strategies in the prevention of antibiotic‐associated diarrhea in hospitalized adult patients.” Additionally, the primary outcome was secondarily analysed using statistical adjustments not prespecified in the protocol. However the unadjusted results are reported as well both in the body and abstract of the paper. We do not consider these concerns sufficient to consider the risk of ‘material’ reporting bias to be high. We therefore assess the risk of material bias here as low |
| Other bias | Unclear risk | “The patient demographics and baseline characteristics were similar for the BIO K+ and placebo groups” “John S. Sampalis and Eliofotisti Psaradellis are employees of JSS Medical Research Inc.; JSS Medical Research Inc. was paid by BIO K+ International Inc. to conduct and manage this study. JSS Medical Research Inc. was responsible for analyzing and interpreting the data as well as writing and reviewing the manuscript. The study was funded by a grant‐in‐aid of research from BIO K+ International Inc” Both study authors are employed by a CRO which was paid by the company (Bio K+) which produces the study product |