| Trial | Risk of 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 | |
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NCT03141177 IMDC favourable risk group |
Low risk of bias | Interactive Response Technology was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 8 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 1.7% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 3% of those who received treatment discontinued due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | High risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per IMDC risk group) were pre‐specified in the protocol and SAP. However, the time point that produced this numerical result was not pre‐specified. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data and inconsistency with pre‐planned analyses. |
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NCT03141177 IMDC intermediate risk group |
Low risk of bias | Interactive Response Technology was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 8 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 1.7% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 3% of those who received treatment discontinued due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | High risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per IMDC risk group) were pre‐specified in the protocol and SAP. However, the time point that produced this numerical result was not pre‐specified. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data and inconsistency with pre‐planned analyses. |
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NCT03141177 IMDC poor risk group |
Low risk of bias | Interactive Response Technology was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 8 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 1.7% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 3% of those who received treatment discontinued due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | High risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per IMDC risk group) were pre‐specified in the protocol and SAP. However, the time point that produced this numerical result was not pre‐specified. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data and inconsistency with pre‐planned analyses. |
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NCT02811861 Comparison 1 (LEN+PEM vs.SUN) Total trial population (combined risk groups) |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 2.8% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Low risk of bias | A study protocol with SAP available. All reported analyses were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 1 (LEN+PEM vs.SUN) MSKCC favourable risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 2.8% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per MSKCC risk group) were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 1 (LEN+PEM vs.SUN) MSKCC intermediate risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 2.8% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per MSKCC risk group) were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 1 (LEN+PEM vs.SUN) MSKCC poor risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 2.8% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per MSKCC risk group) were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 1 (LEN+PEM vs.SUN) IMDC favourable risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was not available for 2 participants randomised to the experimental arm and 4 participants randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without IMDC risk group allocation were excluded from subgroup analyses. | High risk of bias | 2.8% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per IMDC risk group) were pre‐specified in the protocol and SAP. | High risk of bas | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 1 (LEN+PEM vs.SUN) IMDC intermediate risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was not available for 2 participants randomised to the experimental arm and 4 participants randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without IMDC risk group allocation were excluded from subgroup analyses. | High risk of bias | 2.8% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not further explained). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per IMDC risk group) were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 1 (LEN+PEM vs.SUN) IMDC poor risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was not available for 2 participants randomised to the experimental arm and 4 participants randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without IMDC risk group allocation were excluded from subgroup analyses. | High risk of bias | 2.8% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per IMDC) were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 2 (LEN+EVE vs. SUN) Total trial population (combined risk groups) |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 2 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 2.7% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Low risk of bias | A study protocol with SAP available. All reported analyses were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 2 (LEN+EVE vs. SUN) MSKCC favourable risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 2 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 2.7% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per MSKCC risk group) were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 2 (LEN+EVE vs. SUN) MSKCC intermediate risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 2 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bais | 2.7% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not further explained). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per MSKCC risk group) were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 2 (LEN+EVE vs. SUN) MSKCC poor risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 2 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 2.7% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per MSKCC risk group) were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 2 (LEN+EVE vs. SUN) IMDC favourable risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was not available for 6 participants randomised to the experimental arm and 4 participants randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 2 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without IMDC risk group allocation were excluded from subgroup analyses. | High risk of bias | 2.7% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per IMDC risk group) were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information on about missing outcome data. |
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NCT02811861 Comparison 2 (LEN+EVE vs. SUN) IMDC intermediate risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was not available for 6 participants randomised to the experimental arm and 4 participants randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 2 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without IMDC risk group allocation were excluded from subgroup analyses. | High risk of bias | 2.7% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per IMDC risk group) were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT02811861 Comparison 2 (LEN+EVE vs. SUN) IMDC poor risk group |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was not available for 6 participants randomised to the experimental arm and 4 participants randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 2 participants randomised to the experimental arm and 17 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without IMDC risk group allocation were excluded from subgroup analyses. | High risk of bias | 2.7% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. 2% discontinued treatment due to “other” reasons (not explained further). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Low risk of bias | A study protocol with SAP available. All reported subgroup analyses (including analyses per IMDC risk group) were pre‐specified in the protocol and SAP. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data. |
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NCT01108445 Total trial population (combined risk groups) |
Low risk of bias | Participants were randomised in a 1:1 ratio. Randomisation was done under allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned intervention. Only 1 participant withdrew after consent, but before randomisation and before study drug was assigned. The method of analysis was appropriate (ITT). |
Low risk of bias | All 108 participants were evaluable. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT01392183 Total trial population (only intermediate and poor risk groups included in the trial) |
Some concerns | Participants were randomised in a 1:1 ratio, but no information provided about the allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. | High risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. No statement about the method of analysis. | Low risk of bias | Detailed flow diagram provided, no indication of loss to follow‐up. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | High risk of bias | Overall judged high risk of bias due to lack of information about the allocation concealment and method of analysis; missing study protocol and SAP. |
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NCT00334282 Total trial population (combined risk groups) |
Low risk of bias | Interactive voice response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was blinded: both participants and those delivering the intervention were not aware of assigned interventions. The method of analysis was appropriate (ITT). | Low risk of bias | 1.3% of those who received treatment were lost to follow‐up. No analysis to correct for bias, but numbers are low and probably did not have an effect on the outcome. |
Low risk of bias | Outcome assessors were not aware of the assigned intervention. | Low risk of bias | CSR and study protocol with SAP available. All reported analyses were pre‐specified in the protocol and SAP. | Low risk of bias | Overall judged low risk of bias. |
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NCT00065468 Comparison 1 (TEM vs. IFN) Total trial population (only intermediate and poor risk groups included in the trial) |
Some concerns | Participants were randomised, but no information provided about the allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 1 participant randomised to the single‐drug arm and 7 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 1.9% did not receive the intended interventions and therefore did not have outcome data. 2% of those who received treatment were lost to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to lack of information about the allocation concealment; missing study protocol and SAP. |
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NCT00065468 Comparison 2 (IFN+TEM vs. IFN) Total trial population (only intermediate and poor risk groups included in the trial) |
Some concerns | Participants were randomised, but no information provided about the allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 2 participants randomised to the combination arm and 7 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 2.2% did not receive the intended interventions and therefore did not have outcome data. 1.7% of those who received treatment were lost to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to lack of information about the allocation concealment; missing study protocol and SAP. |
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NCT00738530 Total trial population (combined risk groups) |
Low risk of bias | Interactive voice recognition system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was double‐blind: both participants and those delivering the intervention were not aware of assigned interventions. Only 6 participants randomised to the experimental arm and 2 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 1.2% did not receive the intended interventions and therefore did not have outcome data. 4.4% of those who received treatment withdrew consent or were lost to follow‐up before final data cut off for OS analysis. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were not aware of the assigned intervention. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT00738530 MSKCC favourable risk group |
Low risk of bias | Interactive voice recognition system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was not available for 28 participants randomised to the experimental arm and 24 participants randomised to the control arm. | Low risk of bias | The study was double‐blind: both participants and those delivering the intervention were not aware of assigned interventions. Only 6 participants randomised to the experimental arm and 2 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without MSKCC risk group allocation were excluded from subgroup analyses. | Low risk of bias | 1.2% did not receive the intended interventions and therefore did not have outcome data. 4.4% of those who received treatment withdrew consent or were lost to follow‐up before final data cut off for OS analysis. Unclear to which risk group they were assigned to. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were not aware of the assigned intervention. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT00738530 MSKCC intermediate risk group |
Low risk of bias | Interactive voice recognition system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was not available for 28 participants randomised to the experimental arm and 24 participants randomised to the control arm. | Low risk of bias | The study was double‐blind: both participants and those delivering the intervention were not aware of assigned interventions. Only 6 participants randomised to the experimental arm and 2 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without MSKCC risk group allocation were excluded from subgroup analyses. | Low risk of bias | 1.2% did not receive the intended interventions and therefore did not have outcome data. 4.4% of those who received treatment withdrew consent or were lost to follow‐up before final data cut off for OS analysis. Unclear to which risk group they were assigned to. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were not aware of the assigned intervention. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT00738530 MSKCC poor risk group |
Low risk of bias | Interactive voice recognition system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was not available for 28 participants randomised to the experimental arm and 24 participants randomised to the control arm. | Low risk of bias | The study was double‐blind: both participants and those delivering the intervention were not aware of assigned interventions. Only 6 participants randomised to the experimental arm and 2 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without MSKCC risk group allocation were excluded from subgroup analyses. | Low risk of bias | 1.2% did not receive the intended interventions and therefore did not have outcome data. 4.4% of those who received treatment withdrew consent or were lost to follow‐up before final data cut off for OS analysis. Unclear to which risk group they were assigned to. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were not aware of the assigned intervention. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT00072046 Total trial population (combined risk groups) |
Some concerns | Participants were randomised via a stratified random block design, but no information provided about the allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 13 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 2.2% did not receive the intended interventions and therefore did not have outcome data. Of those who received treatment, less than 1% were lost to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement (objective outcome). | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing information about the allocation concealment; missing study protocol and SAP. |
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NCT00072046 MSKCC favourable risk group |
Some concerns | Participants were randomised via a stratified random block design, but no information provided about the allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 13 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 2.2% did not receive the intended interventions and therefore did not have outcome data. Of those who received treatment, less than 1% were lost to follow‐up. Unclear to which risk group they were assigned to. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing information about the allocation concealment; missing study protocol and SAP. |
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NCT00072046 MSKCC intermediate risk group |
Some concerns | Participants were randomised via a stratified random block design, but no information provided about the allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 13 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 2.2% did not receive the intended interventions and therefore did not have outcome data. Of those who received treatment, less than 1% were lost to follow‐up. Unclear to which risk group they were assigned to. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing information about the allocation concealment; missing study protocol and SAP. |
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NCT00072046 MSKCC poor risk group |
Some concerns | Participants were randomised via a stratified random block design, but no information provided about the allocation concealment. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 13 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 2.2% did not receive the intended interventions and therefore did not have outcome data. Of those who received treatment, less than 1% were lost to follow‐up. Unclear to which risk group they were assigned to. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing information about the allocation concealment; missing study protocol and SAP. |
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NCT00609401 Total trial population (combined risk groups) |
Low risk of bias | Randomisation was performed centrally. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. The method of analysis was appropriate (ITT). | Low risk of bias | 6.3% were lost to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT00081614 Total trial population (only favourable and intermediate risk groups included in the trial) |
Low risk of bias | Interactive voice response service was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was double‐blind: both participants and those delivering the intervention were not aware of assigned interventions. The method of analysis was appropriate (ITT). | Low risk of bias | 1 participant randomised to the experimental arm was lost to follow‐up, which probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were not aware of the assigned intervention. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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Jonasch 2010 Total trial population (combined risk groups) |
Low risk | Randomisation method appropriate and allocation concealed. No imbalances. | Low risk of bias | No information provided about whether the participants or those delivering the intervention were blinded or not. Only 1 participant randomised to the experimental arm did not receive any treatment. The method of analysis was appropriate (ITT). |
Low risk | 1 participant did not receive the intended intervention and therefore did not have outcome data. Of those who received treatment, 8.8% came off study before the first 8‐week response assessment. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement (objective outcome). | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT00098657/NCT00083889 Total trial population (combined risk groups) |
Some concerns | Participants were randomised in a 1:1 ratio, but it is not mentioned who conducted the randomisation or whether it was conducted centrally so that nobody could foresee assignment. However, there were no baseline imbalances that would suggest a problem with randomisation. | Some concerns | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 15 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 2% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement (objective outcome). | Some concerns | No study protocol or SAP available. | High risk of bias | Overall judged high risk of bias due to lack of information about the randomisation process and allocation concealment; deviations from intended interventions only in the control group; lack of information about missing data; missing study protocol and SAP. |
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NCT00098657/NCT00083889 MSKCC intermediate risk group |
Some concerns | Participants were randomised in a 1:1 ratio, but it is not mentioned who conducted the randomisation or whether it was conducted centrally so that nobody could foresee assignment. However, there were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Some concerns | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 15 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 2% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement (objective outcome). | Some concerns | No study protocol or SAP available. | High risk of bias | Overall judged high risk of bias due to lack of information about the randomisation process and allocation concealment; deviations from intended interventions only in the control group; lack of information about missing data; missing study protocol and SAP. |
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NCT00098657/NCT00083889 MSKCC poor risk group |
Some concerns | Participants were randomised in a 1:1 ratio, but it is not mentioned who conducted the randomisation or whether it was conducted centrally so that nobody could foresee assignment. However, there were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Some concerns | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 15 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 2% did not receive the intended interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement (objective outcome). | Some concerns | No study protocol or SAP available. | High risk of bias | Overall judged high risk of bias due to lack of information about the randomisation process and allocation concealment; deviations from intended interventions only in the control group; lack of information about missing data; missing study protocol and SAP. |
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NCT00920816 Total trial population (combined risk groups) |
Low risk of bias | A centralised registration system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 1% did not receive the intended interventions and therefore did not have outcome data. 2.1% of those who received treatment were lost to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were not aware of the assigned intervention. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT01024920 Total trial population (combined risk groups) |
Low risk of bias | Interactive voice randomisation system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm did not receive any treatment. The method of analysis was appropriate. | Low risk of bias | 3% did not receive the intended interventions and therefore did not have outcome data. 1 participant randomised to the control arm was lost to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT00631371 Total trial population (combined risk groups) |
Low risk of bias | A computerised centrally located randomisation system was used. There were no baseline imbalances that would suggest a problem with randomisation. |
Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 7 participants randomised to the experimental arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | Less than 1% did not receive the intended interventions and therefore did not have outcome data. 5.5% of those who received treatment were lost to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT01835158 Total trial population (only intermediate and poor risk groups included in the trial) |
Low risk of bias | Randomisation was performed centrally. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 1 participant randomised to the experimental arm and 6 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | High risk of bias | 4.5% did not receive the intended interventions and therefore did not have outcome data. There is a statement about loss to follow‐up, but not how many. |
Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | Study protocol available with some statistical considerations briefly described, but no separate SAP available to fully check the pre‐planned analyses. | High risk of bias | Overall judged high risk of bias due to lack of information about missing outcome data; missing SAP. |
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NCT02231749 Total trial population (combined risk groups) |
Low risk of bias | Interactive voice response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 11 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 1.3% did not receive the intended interventions and therefore did not have outcome data. Less than 1% of those who received treatment were lost to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement. | Low risk of bias | Study protocol and SAP available. Final revisions of both done before data cutoff (with extended follow‐up). Analyses were preplanned and reported. | Low risk of bias | Overall judged low risk of bias. |
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NCT02231749 IMDC favourable risk group |
Low risk of bias | Interactive voice response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 11 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 1.3% did not receive the intended interventions and therefore did not have outcome data. Less than 1% of those who received treatment were lost to follow‐up. Unclear to which risk group they were assigned to. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement. | Low risk of bias | Study protocol and SAP available. Final revisions of both done before data cutoff (with extended follow‐up). Analyses were preplanned and reported. | Low risk of bias | Overall judged low risk of bias. |
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NCT02231749 IMDC intermediate&poor risk groups combined |
Low risk of bias | Interactive voice response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned Only 3 participants randomised to the experimental arm and 11 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 1.3% did not receive the intended interventions and therefore did not have outcome data. Less than 1% of those who received treatment were lost to follow‐up. Unclear to which risk group they were assigned to. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement. | Low risk of bias | Study protocol and SAP available. Final revisions of both done before data cutoff (with extended follow‐up). Analyses were preplanned and reported. | Low risk of bias | Overall judged low risk of bias. |
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NCT01984242 Comparison 1 (ATE vs. SUN) Total trial population (combined risk groups) |
Low risk of bias | Interactive voice/web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 1 participant randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 0.3% did not receive the intended interventions and therefore did not have outcome data. 1.5% of those who received treatment were lost to follow‐up. However, these numbers are very low and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT01984242 Comparison 2 (ATE+BEV vs. SUN) Total trial population (combined risk groups) |
Low risk of bias | Interactive voice/web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 1 participant randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 0.3% did not receive the intended interventions and therefore did not have outcome data. 3.5% of those who received treatment were lost to follow‐up. However, these numbers are very low and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to missing study protocol and SAP. |
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NCT02420821 Total trial population (combined risk groups) |
Low risk of bias | Interactive voice and web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk if bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 15 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | 2% did not receive the intended interventions and therefore did not have outcome data. Less than 1% were lost to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | Outcome assessors were aware of the assigned intervention, but knowledge of intervention received could not have affected outcome measurement. | Low risk of bias | Study protocol and SAP available. All reported analyses were pre‐specified in the protocol and SAP. | Low risk of bias | Overall judged low risk of bias. |
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NCT02684006 IMDC favourable risk group |
Low risk of bias | Interactive voice response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was not available for 5 participants randomised to the experimental arm and 1 participant randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 8 participants randomised to the experimental arm and 5 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate. Participants without IMDC risk group allocation were excluded from the analysis. |
Some concerns | 1.5% did not receive the intended interventions and therefore did not have outcome data. No information about study flow for the second interim analysis (which is the result considered in this review). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | High risk of bias | Study protocol and SAP available but discrepancies were found between statements in the publications and the SAP about the pre‐specification of subgroup analyses. However, the time point (third interim analysis for OS) was pre‐specified. | High risk of bias | Overall judged high risk of bias due to lack of information about potential losses of follow‐up; lack of information about the subgroup analyses in the study protocol and SAP. |
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NCT02684006 IMDC intermediate risk group |
Low risk of bias | Interactive voice response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was not available for 5 participants randomised to the experimental arm and 1 participant randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 8 participants randomised to the experimental arm and 5 participants randomised to the control arm did not receive any treatment. unclear. The method of analysis was appropriate. Participants without IMDC risk group allocation were excluded from subgroup analyses. |
Some concerns | 1.5% did not receive the intended interventions and therefore did not have outcome data. No information about study flow for the second interim analysis (which is the result considered in this review). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | High risk of bias | Study protocol and SAP available but discrepancies were found between statements in the publications and the SAP about the pre‐specification of subgroup analyses. However, the time point (third interim analysis for OS) was pre‐specified. | High risk of bias | Overall judged high risk of bias due to lack of information about potential losses of follow‐up; lack of information about the subgroup analyses in the study protocol and SAP. |
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NCT02684006 IMDC poor risk group |
Low risk of bias | Interactive voice response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. IMDC risk group was not available for 5 participants randomised to the experimental arm and 1 participant randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 8 participants randomised to the experimental arm and 5 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate. Participants without IMDC risk group allocation were excluded from subgroup analyses. |
Some concerns | 1.5% did not receive the intended interventions and therefore did not have outcome data. No information about study flow for the second interim analysis (which is the result considered in this review). | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | High risk of bias | Study protocol and SAP available but discrepancies were found between statements in the publications and the SAP about the pre‐specification of subgroup analyses. However, the time point (third interim analysis for OS) was pre‐specified. | High risk of bias | Overall judged high risk of bias due to lack of information about potential losses of follow‐up; lack of information about the subgroup analyses in the study protocol and SAP. |
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NCT02853331 Total trial population (combined risk groups) |
Low risk of bias | Interactive voice response system or integrated web response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 4 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | Less than 1% did not receive the intended interventions and therefore did not have outcome data. No indication of loss to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Low risk of bias | Study protocol and SAP available. All reported analyses were pre‐specified in the protocol and SAP. | Low risk of bias | Overall judged low risk of bias. |
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NCT00719264 Total trial population (combined risk groups) |
Some concerns | Participants were randomised in a 1:1 ratio, but no information provided about who conducted the randomisation and whether the allocation was concealed. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 1 participant randomised to the experimental arm and 2 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate. | Low risk of bias | Less than 1% did not receive the intended interventions and therefore did not have outcome data. Less than 1% of those who received treatment were lost to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | Some concerns | Overall judged some concerns due to lack of information about the randomisation and allocation concealment; missing study protocol and SAP. |
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NCT00720941 Total trial population (combined risk groups) |
Low risk of bias | Interactive voice response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 5 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). | Low risk of bias | Less than 1% did not receive the intended interventions and therefore did not have outcome data. 2.9% of those who received treatment were lost to follow‐up. However, these numbers are small and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Low risk of bias | CSR and study protocol with SAP available. All reported analyses were pre‐specified in the protocol and SAP. | Low risk of bias | Overall judged low risk of bias. |
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NCT00720941 MSKCC favourable risk group |
Low risk of bias | Interactive voice response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was not available for 17 participants randomised to the experimental arm and 21 participants randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 5 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without MSKCC risk group allocation were excluded from subgroup analyses. |
Low risk of bias | Less than 1% did not receive the intended interventions and therefore did not have outcome data. 2.9% of those who received treatment were lost to follow‐up. Unclear to which risk group they were assigned to. However, these numbers are small and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | High risk of bias | A post‐hoc analysis according to risk group was conducted. | High risk of bias | Overall judged high risk of bias due to post‐hoc analysis. |
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NCT00720941 MSKCC intermediate risk group |
Low risk of bias | Interactive voice response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was not available for 17 participants randomised to the experimental arm and 21 participants randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 5 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without MSKCC risk group allocation were excluded from subgroup analyses. |
Low risk of bias | Less than 1% did not receive the intended interventions and therefore did not have outcome data. 2.9% of those who received treatment were lost to follow‐up. Unclear to which risk group they were assigned to. However, these numbers are small and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | High risk of bias | A post‐hoc analysis according to risk group was conducted. | High risk of bias | Overall judged high risk of bias due to post‐hoc analysis. |
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NCT00720941 MSKCC poor risk group |
Low risk of bias | Interactive voice response system was used for randomisation. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was not available for 17 participants randomised to the experimental arm and 21 participants randomised to the control arm. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 3 participants randomised to the experimental arm and 5 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). Participants without MSKCC risk group allocation were excluded from subgroup analyses. |
Low risk of bias | Less than 1% did not receive the intended interventions and therefore did not have outcome data. 2.9% of those who received treatment were lost to follow‐up. Unclear to which risk group they were assigned to. However, these numbers are small and probably did not have an effect on the outcome. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | High risk of bias | A post‐hoc analysis according to risk group was conducted. | High risk of bias | Overall judged high risk of bias due to post‐hoc analysis. |
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NCT00420888 Total trial population |
Some concerns | Participants were randomised in a 1:1 ratio, but no information provided about who conducted the randomisation and whether the allocation was concealed. There were no baseline imbalances that would suggest a problem with randomisation. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 8 participants did not receive any treatment. The method of analysis was appropriate (ITT). |
High risk of bias | 1.5% did not receive the assigned interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available | High risk of bias | Overall judged high risk of bias due to lack of information about randomisation process and allocation concealment; missing outcome data; missing study protocol and SAP. |
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NCT00420888 MSKCC favourable risk group |
Some concerns | Participants were randomised in a 1:1 ratio, but no information provided about who conducted the randomisation and whether the allocation was concealed. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 8 participants did not receive any treatment. The method of analysis was appropriate (ITT). |
High risk of bias | 1.5% did not receive the assigned interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available | High risk of bias | Overall judged high risk of bias due to lack of information about randomisation process and allocation concealment; missing outcome data; missing study protocol and SAP. |
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NCT00420888 MSKCC intermediate risk group |
Some concerns | Participants were randomised in a 1:1 ratio, but no information provided about who conducted the randomisation and whether the allocation was concealed. There were no baseline imbalances that would suggest a problem with randomisation. MSKCC risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 8 participants did not receive any treatment. The method of analysis was appropriate (ITT). |
High risk of bias | 1.5% did not receive the assigned interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available | High risk of bias | Overall judged high risk of bias due to lack of information about randomisation process and allocation concealment; missing outcome data; missing study protocol and SAP. |
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NCT00420888 IMDC favourable risk group |
Some concerns | Participants were randomised in a 1:1 ratio, but no information provided about who conducted the randomisation and whether the allocation was concealed. There were no baseline imbalances that would suggest a problem with randomisation. HENG risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 8 participants did not receive any treatment. The method of analysis was appropriate (ITT). |
High risk of bias | 1.5% did not receive the assigned interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available | High risk of bias | Overall judged high risk of bias due to lack of information about randomisation process and allocation concealment; missing outcome data; missing study protocol and SAP. |
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NCT00420888 IMDC intermediate risk group |
Some concerns | Participants were randomised in a 1:1 ratio, but no information provided about who conducted the randomisation and whether the allocation was concealed There were no baseline imbalances that would suggest a problem with randomisation. HENG risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 8 participants did not receive any treatment. The method of analysis was appropriate (ITT). |
High risk of bias | 1.5% did not receive the assigned interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available | High risk of bias | Overall judged high risk of bias due to lack of information about randomisation process and allocation concealment; missing outcome data; missing study protocol and SAP. |
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NCT00420888 IMDC poor risk group |
Some concerns | Participants were randomised in a 1:1 ratio, but no information provided about who conducted the randomisation and whether the allocation was concealed. There were no baseline imbalances that would suggest a problem with randomisation. HENG risk group was available for all randomised participants. | Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 8 participants did not receive any treatment. The method of analysis was appropriate (ITT). |
High risk of bias | 1.5% did not receive the assigned interventions and therefore did not have outcome data. No information whether there was loss to follow‐up. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available | High risk of bias | Overall judged high risk of bias due to lack of information about randomisation process and allocation concealment; missing outcome data; missing study protocol and SAP. |
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NCT00979966 Total trial population |
High risk of bias | Participants were randomised in a 1:1 ratio, but no information provided about who conducted the randomisation and whether the allocation was concealed. There were baseline imbalances that could suggest a problem with randomisation. | High risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. No information whether there were deviations form intended interventions and no information provided about the method of analysis. | High risk of bias | No information whether there was loss to follow‐up. | Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | No study protocol or SAP available. | High risk of bias | Overall judged high risk of bias due to lack of information about the randomisation, the allocation concealment, the deviations from intended interventions, the method of analysis and missing outcome data; missing study protocol and SAP. |
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NCT02761057 SWOG Comparison 1 (CAB vs. SUN) Total trial population (combined risk groups) |
Low risk of bias | Randomisation was done by the Statistical Center. There were no baseline imbalances that would suggest a problem with randomisation. |
Low risk of bias | The study was open‐label: both participants and those delivering the intervention were aware of assigned interventions. Only 2 participants randomised to the experimental arm and 2 participants randomised to the control arm did not receive any treatment. The method of analysis was appropriate (ITT). |
Low risk of bias | 4.3% did not receive the intended interventions and therefore did not have outcome data. 2.2% had no protocol treatment. Only 1 participant was lost to follow‐up. However, these numbers are low and probably did not have an effect on the outcome. |
Low risk of bias | No precise information provided about the outcome assessors, but either way knowledge of intervention received could not have affected outcome measurement. | Some concerns | Study protocol available, but no original SAP. | Some concerns | Overall judged some concerns due to missing SAP. |
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