https://doi.org/10.1002/14651858.CD015391
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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 | |
Lenze 2020 | Low risk of bias |
Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated that stratified by age (18-44, 45-54, 55-64, and ≥65 years)16 and sex. Treatments were randomly allocated using alternating block sizes of 2 and 4. Randomization allocation was conducted via REDCap, which displayed randomization assignment to the laboratory manager (J.S.), who prepared the study materials, including the study drug or placebo. All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment." "Participants were well-matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups." |
Low risk of bias |
Placebo controlled trial. All outcome assessors, investigators, and research staff who were in There is a substantial number of participants who did not complete the study. There were 18 out of 80 (22.5%) in intervention group and 19 out of 72 (26.4%) in the placebo group. Patients were analysed according to randomization group. |
High risk of bias |
37 study participants did not finish the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study. |
Low risk of bias |
No detailed information on outcome measurement reported. Medical records were used to measure outcomes that were not self-reported. No patients died during the trial. |
Low risk of bias |
The primary analysis reported agrees with that of the protocol. |
High risk of bias |
Quote: "Patients were randomized 1:1 to fluvoxamine or matching "Participants were well-matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups."
37 study participants did not finish the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study.
|
TOGETHER 2021 | Low risk of bias |
Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)." |
Low risk of bias |
Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group." Comment: Patients were analysed according to randomization group with intention-to treat analyses. |
Low risk of bias |
Quote: "84 participants stopped fluvoxamine and 64 participants stopped placebo owing to issues of tolerability." |
Low risk of bias |
Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing. We collected outcome data irrespective of whether |
Low risk of bias |
Comment: The primary analysis reported in the paper agrees with that of the protocol. |
Low risk of bias |
Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)." Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group." Comment: Patients were analysed according to randomization group with intention-to treat analyses. Quote: "84 participants stopped fluvoxamine and 64 participants Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing. Comment: The primary analysis reported in the paper agrees with that of the protocol. |
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 | |
Lenze 2020 | Low risk of bias |
Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated that stratified by age (18-44, 45-54, 55-64, and ≥65 years)16 and sex. Treatments were randomly allocated using alternating block sizes of 2 and 4. Randomization allocation was conducted via REDCap, which displayed randomization assignment to the laboratory manager (J.S.), who prepared the study materials, including the study drug or placebo. All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment." "Participants were well-matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups." |
Low risk of bias |
All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment. Patients were analyzed according to randomization group. |
Low risk of bias |
Although 37 study participants did not finish the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study, the authors performed a senstivity analysis to assess the missing data. |
Low risk of bias |
In this case we consider hospitalisation as obejctive enough to allow for an unbiased assessment. Study personnel and participants were blinded to the intervention. |
Low risk of bias |
The primary analysis reported in the paper agrees with that of the protocol. Unlikely that multiple outcome measures or analyses were used since 0 patients died during the trial. |
Low risk of bias |
No concerns. |
TOGETHER 2021 | Low risk of bias |
Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)." |
Low risk of bias |
Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group." Comment: Patients were analysed according to randomization group with intention-to treat analyses. |
Low risk of bias |
Quote: "84 participants stopped fluvoxamine and 64 participants stopped placebo owing to issues of tolerability." |
Low risk of bias |
Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or |
Low risk of bias |
Comment: The primary analysis reported in the publication agrees with that of the protocol. Numerical results are unlikely to be selected from multiple outcome measures or analyses. Outcomes are sufficiently different and details are reported for each measurement separately. |
Low risk of bias |
Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)." Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group." Comment: Patients were analysed according to randomisation group with intention-to treat analyses. Quote: "84 participants stopped fluvoxamine and 64 participants Quote: "Study personnel collected outcome data on days 1, 2, 3, Comment: The primary analysis reported in the paper agrees with that of the protocol. |
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 | |
Lenze 2020 | Low risk of bias |
Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated that stratified by age (18-44, 45-54, 55-64, and ≥65 years)16 and sex. Treatments were randomly allocated using alternating block sizes of 2 and 4. Randomization allocation was conducted via REDCap, which displayed randomization assignment to the laboratory manager (J.S.), who prepared the study materials, including the study drug or placebo. All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment." "Participants were well-matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups." |
Low risk of bias |
Placebo controlled trial. All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment. There is a substantial number of participants who did not complete the study. There were 18 out of 80 (22.5%) in the intervention group and 19 out of 72 (26.4%) in the placebo group. Comment: For missing data, the researchers compared available scores with missing scores to check if the missing scores were non-random. |
High risk of bias |
37 study participants did not complete the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study. Outcome data could potentially be missing when participants experienced serious adverse events. |
High risk of bias |
Quote: "Adverse events and serious adverse events were recorded each day via participant self-report for 15 days after randomization." |
Low risk of bias |
The protocol states: "we will assess for adverse events (including serious adverse events) daily via participant self-report during the first 15 days, and then again at the end of the study." |
High risk of bias |
Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated "Participants were well matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups." There is a substantial number of participants who did not complete the study. There were 18 in intervention group and 19 in the placebo group. Comment: For missing data, the researchers compared available scores with missing scores to check if the missing scores were non-random. 37 study participants did not finish the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study. The outcomes for the missing observations would have been significantly different from the final participants analysed. The protocol states: "we will assess for adverse events (including serious adverse events) daily via participant self-report during the first 15 days, and then again at the end of the study." |
TOGETHER 2021 | Low risk of bias |
Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)." |
Low risk of bias |
Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group." Comment: Patients were analysed according to randomization group with intention-to treat analyses. |
Low risk of bias |
Quote: "84 participants stopped fluvoxamine and 64 participants stopped placebo owing to issues of tolerability." |
High risk of bias |
Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing. We collected outcome data irrespective of whether participants took study medication."; "All serious and non-serious adverse events were reported to study personnel as per local regulatory |
Low risk of bias |
Comment: The primary analysis reported in the paper agrees with that of the protocol. Numerical results are unlikely to be selected from multiple outcome measures or analyses. |
High risk of bias |
Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)." Quote: "The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group." Comment: Patients were analysed according to randomization group with intention-to treat analyses. Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing. Comment: The primary analysis reported in the paper agrees with that of the protocol. |
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 | |
Lenze 2020 | Low risk of bias |
Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated that stratified by age (18-44, 45-54, 55-64, and ≥65 years)16 and sex. Treatments were randomly allocated using alternating block sizes of 2 and 4. Randomization allocation was conducted via REDCap, which displayed randomization assignment to the laboratory manager (J.S.), who prepared the study materials, including the study drug or placebo. All outcome assessors, investigators, and research staff who were in contact with participants were blinded to participant treatment assignment." "Participants were well-matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups." |
Low risk of bias |
Placebo controlled trial. All outcome assessors, investigators, and research staff who were in Comment: For missing data, the researchers compared available scores with missing scores to check if the missing scores were non-random. |
High risk of bias |
37 study participants did not finish the study. There were 18 out of 80 (22.5%) in the intervention group and 19 out of 72 (26.4%) in the placebo group. No evidence to support that the results were not bias by missing outcome data. The outcomes for the missing observations would have been significantly different from the final participants analysed. |
High risk of bias |
Quote: "Adverse events and serious adverse events were recorded each day via participant self-report for 15 days after randomization." |
Low risk of bias |
The protocol states: "we will assess for adverse events (including serious adverse events) daily via participant self-report during the first 15 days, and then again at the end of the study." |
High risk of bias |
Quote: "Patients were randomized 1:1 to fluvoxamine or matching placebo capsules. Randomization schedules were generated "Participants were well matched in demographic and clinical characteristics. The baseline oxygen saturation level did not differ between the groups."
37 study participants did not finish the study. 18 patients in the intervention group and 19 patients in the placebo group did not complete the study. The outcomes for the missing observations would have been significantly different from the final participants analysed. In the protocol it states: "we will assess for adverse events (including serious adverse events) daily via participant self-report during the first 15 days, and then again at the end of the study." |
TOGETHER 2021 | Low risk of bias |
Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Patients were randomly assigned (1:1) by means of a block randomisation procedure for each participating site, stratified by age (<50 years or ≥50 years)." |
Low risk of bias |
No, The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group. Comment: Patients were analysed according to randomization group with intention-to treat analysis. |
Low risk of bias |
Quote: "84 participants stopped fluvoxamine and 64 participants stopped placebo owing to issues of tolerability." |
High risk of bias |
Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing. We collected outcome data irrespective of whether |
Low risk of bias |
Comment: The primary analysis reported in the paper agrees with that of the protocol. Numerical results are unlikely to be selected from multiple outcome measures or analyses. |
High risk of bias |
Quote: "Participants were randomly assigned by means of a centralised core randomisation process handled by an independent unmasked pharmacist who was not aware of any protocol-related procedures and contracted specifically for this process. Sites requested randomisation by text message to the pharmacist at the coordinating centre. "Participants were well matched in demographic and clinical characteristics." The trial team, site staff, and patients were masked to treatment allocation. The active drugs and the placebo pills were packaged in identically shaped bottles and labelled with alphabet letters corresponding to the active group or placebo group. Comment: Patients were analysed according to randomization group with intention-to treat analyses. Quote: "84 participants stopped fluvoxamine and 64 participants stopped placebo owing to issues of tolerability." Quote: "Study personnel collected outcome data on days 1, 2, 3, 4, 5, 7, 10, 14, and 28 in person or via telephone contact or social media applications using video-teleconferencing.
The primary analysis reported in the paper agrees with that of the protocol. Numerical results are unlikely to be selected from multiple outcome measures or analyses. |