Risk of bias for analysis 1.10 All‐cause mortality: sensitivity analysis: fixed‐effect model.
| Study | Bias | |||||||||||
| Randomisation process | Deviations from intended interventions | Missing outcome data | Measurement of the outcome | Selection of the reported results | Overall | |||||||
| Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | Authors' judgement | Support for judgement | |
| Cammarota 2015 | Low risk of bias | Quote from article: "Blocked randomization of subjects was performed by an external person not involved in the study. An online random number generator software was used to provide random permuted blocks with a block size of six and an equal allocation ratio; the sequence was concealed until the interventions were assigned." Comment: We think the allocation sequence was random and appropriately concealed in this study and the baseline characteristics of the two groups were comparable. |
Low risk of bias | The study was not blinded however we do not believe there was a deviation from intended intervention due to non‐blinding nor did this affect the outcome measured as we included the analyzed data on an intention to treat basis. | Low risk of bias | There was no missing data at the end of the study period. | Low risk of bias | The study was open‐label. However, the outcome of all‐cause mortality is an observer‐reported outcome not involving judgement hence there is a low risk of bias. | Low risk of bias | The clinical trial was registered at clinicaltrial.gov (NCT02148601). The study was conducted in accordance with the Consolidated Standards of Reporting Trials (CONSORT) Statement. There were no concerns about selective reporting for this outcome. | Low risk of bias | Even though the study was open‐label, we did not have any major concerns about bias in the measurement of this outcome as all‐cause mortality is an observer‐reported outcome not involving judgement hence the assessment is not likely to be influenced by knowledge of intervention received. Moreover, intention to treat analysis was performed. |
| Hota 2017 | Some concerns | No information was available on sequence generation and concealment of allocation sequence. However, the baseline characteristics of both groups were similar. We contacted the authors for further information on the randomization process but did not get a reply. | Low risk of bias | The study was not blinded however we do not believe there was a significant deviation from intended intervention due to non‐blinding nor did this affect the outcome measured. The authors of the study performed a per‐protocol analysis and we included the intention to treat analysis by considering all the participants who were randomized to FMT and vancomycin group and assumed that two participants excluded by the study authors in the analysis did not have the outcome. | Low risk of bias | Two participants were excluded from the vancomycin group, one withdrew and one was withdrawn by the investigator due to non‐compliance to protocol. We included all participants in the intention‐to‐treat analysis and assumed that those excluded did not experience the outcome. This missing data is less likely to create a bias for this outcome. | Low risk of bias | The study was open‐label. However, the outcome of all‐cause mortality is an observer‐reported outcome not involving judgement hence there is a low risk of bias. | Low risk of bias | The study was registered at clinicaltrial.gov (NCT01226992). We did not have any major concerns about selective reporting for this outcome. | Low risk of bias | Even though we had some concerns about the lack of description of methods of randomization process, we did not think that this study was at high risk of bias. The two groups were balanced at the start of the trial. Even though this was an open label study the outcome measured was objective hence low risk of bias from non‐blinding. |
| Hvas 2019 | Some concerns | No information was available on allocation sequence and concealment of allocation sequence. However, the baseline characteristics of both groups were similar. We contacted the authors for further information on the randomization process but did not get a reply. | Low risk of bias | The study was not blinded however we do not believe there were significant deviations from the intended treatment due to non‐blinding as all participants received allocated intervention and authors of the study performed intention to treat analysis. | Low risk of bias | There was no attrition and data were available for all the participants for this outcome. | Low risk of bias | The study was open‐label. However, the outcome of all‐cause mortality is an observer‐reported outcome not involving judgement hence there is a low risk of bias. | Low risk of bias | The trial was registered at clinicaltrial.gov (NCT02743234). We did not have any concerns about selective reporting for this outcome. | Low risk of bias | Even though we had some concerns about the lack of description of methods of randomization process and that study was open label, we did not consider this study was at high risk for bias for this outcome. All the study groups were similar at the start of the trial and that outcome measured was objective in nature. |
| Kelly 2016 | Low risk of bias | Quote from article: "Patients were equally allocated to the donor and autologous FMT groups via block randomization by C difficile positivity at baseline, with stratification by study site." Comment: The allocation sequence was random and appropriately concealed in this study and the baseline characteristics of the two groups were comparable. |
Low risk of bias | This was a double‐blinded study and the authors performed an intention to treat analysis. | Low risk of bias | Two patients were lost to follow‐up in the control and one patient in the intervention group. All participants were considered in the intention to treat analysis. | Low risk of bias | The study was double‐blind, hence we did not have any concerns about the risk of bias in the measurement of this outcome. | Low risk of bias | The trial was registered at clinicaltrial.gov (NCT01703494). We did not have any concerns about selective reporting for this outcome. | Low risk of bias | This was a very well conducted double blinded study with no major concerns about risk of bias for any of the domains considered. |
| Rode 2021 | Low risk of bias | Quote from article: "Computer‐generated stratified randomization in blocks of six was used with allocation concealment in sealed opaque envelopes with sequential numbers for each stratum. " Comment: The allocation sequence was random and appropriately concealed in this study and the baseline characteristics of the two groups were comparable. |
Low risk of bias | The study was not blinded however we do not believe there was a deviation from intended intervention due to non‐blinding nor did this affect the outcome measured as we included the analyzed data on an intention to treat basis by assuming that two participants who did not complete the study did not have the outcome. | Low risk of bias | We analyzed data on an intention‐to‐treat basis, hence there is a low risk of bias from missing data on two participants. | Low risk of bias | The study was open‐label. However, the outcome of all‐cause mortality is an observer‐reported outcome not involving judgement hence there is a low risk of bias. | Low risk of bias | The trial was registered at ClinicalTrials.gov (NCT02774382). We did not have any major concerns about selective reporting for this outcome. | Low risk of bias | Even though the study was open‐label, we did not have any major concerns about bias in the measurement of this outcome due to the objective nature of outcomes measured and intention to treat analysis. |
| van Nood 2013 | Low risk of bias | Quote from protocol: "Patients will be randomized by a computer according to their first, second or >2 relapses, and hospitalization status." Quote from Supplementary Appendix: ''To achieve adequate allocation concealment, each patient was randomized by applying automated biased coin minimization in ALEA with stratification for hospitalization status (clinical or outpatient) and the number of previous recurrences (1, 2, >2). The coin bias factor was set at 3, the bias coin lower threshold at 2. Study physicians at the coordinating center in charge of randomization were unaware of the model specifications used.'' Comment: The allocation sequence was random and appropriately concealed in this study and the baseline characteristics of the two groups were comparable. |
Low risk of bias | The authors analyzed data on a modified intention‐to‐treat basis with the exclusion of one patient who required high dose prednisolone treatment after randomization but before the study treatment was initiated. The study was not blinded however we do not believe there was a deviation from intended intervention due to non‐blinding nor did this affect the outcome measured as we included the analyzed data on an intention to treat basis by assuming that two participants who did not complete the study did not have the outcome. | Low risk of bias | All participants were included in the intention to treat analysis while assessing all‐cause mortality. | Low risk of bias | The study was open‐label. However, the outcome of all‐cause mortality is an observer‐reported outcome not involving judgement hence there is a low risk of bias. | Low risk of bias | The trial was registered at the Netherlands Trial Register number, NTR1177. We did not have any concerns about selective outcome reporting for this outcome. | Low risk of bias | Even though the study was open‐label, we did not have any major concerns about bias in the measurement of this outcome as all‐cause mortality is an observer‐reported outcome not involving judgement hence the assessment is not likely to be influenced by knowledge of intervention received. |