| 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 |
| Subgroup 4.3.1 Adults |
| Davies 2014 |
Low risk of bias |
At the randomisation visit (visit 2) the participants were to be randomised to either insulin degludec or insulin detemir, both in combination with insulin aspart. The randomisation was to be carried out in a 2:1 manner using the Interactive Voice/Web Response System IV/WRS. The trial was stratified according to region with 4 levels: Europe (Italy, UK, Macedonia and Finland), Japan, India and South America (Brazil). There were no relevant baseline imbalances. |
Low risk of bias |
Open‐label trial design. The statistical evaluation of the full analysis set (FAS) was to follow the intention‐to‐treat (ITT) principle. |
Low risk of bias |
Withdrawals and reasons for withdrawal were documented, did not differ substantially between intervention groups and did not appear to be related to health status. Full Analysis Set (FAS) included all randomised participants. The statistical evaluation of the FAS was to follow the intention‐to‐treat (ITT) principle and participants were to contribute to the evaluation “as randomised”. Safety analysis set included all participants who received at least one dose of the investigational product or its comparator. Participants in the safety set were to contribute to the evaluation “as treated”. Unless otherwise specified missing values (including intermittent missing values) were imputed using the last observation carried forward (LOCF) method. Missing observations were considered missing at random in all analyses. |
Low risk of bias |
Open‐label design with outcome measure unlikely influenced by lack of blinding. |
Low risk of bias |
Data from full clinical study report. Only one measurement and result provided for the time point selected by review authors. |
Low risk of bias |
No risk of bias identified. |
| Subgroup 4.3.2 Children |
| BEGIN Young |
Low risk of bias |
Participants were allocated to treatment with insulin degludec or insulin detemir in a 1:1 ratio. Randomisation was carried out using a central interactive voice/web response system (IV/WRS). Randomisation was stratified according to 3 age groups: 1 to less than 6 years; 6 to less than 12 years; 12 to less than 18 years of age. There were no relevant baseline imbalances. |
Low risk of bias |
Open‐label trial design. The internal Novo Nordisk safety committee and the external data monitoring committee (DMC) reviewed safety data on an ongoing basis. The internal safety committee was blinded and the DMC was unblinded. All analyses and summary of efficacy endpoints, and formal statistical analyses related to safety endpoints were based on the full analysis set (FAS). The statistical evaluation of the FAS was to follow the intention‐to‐treat (ITT) principle and participants contributed to the evaluation “as randomised”. |
Low risk of bias |
Withdrawals and reasons for withdrawal were documented, did not differ substantially between intervention groups and did not appear to be related to health status. The full analysis set (FAS) included all randomised participants. The statistical evaluation of the FAS was to follow the intention‐to‐treat (ITT) principle and participants contributed to the evaluation “as randomised”. The safety analysis set included all participants receiving at least one dose of the investigational product. Participants in the safety set were to contribute to the evaluation “as treated”. All analyses and summary of efficacy endpoints, and formal statistical analyses related to safety endpoints were based on the full analysis set (FAS). Only endpoints derived after 26 weeks of treatment were to be analysed statistically. Unless otherwise specified, missing values (including intermittent missing values) were imputed using the last‐observation‐carried‐forward (LOCF) method. External classification of severe hypoglycaemia was performed blinded. |
Low risk of bias |
External classification of severe hypoglycaemia was performed blinded and outcome measure unlikely influenced by potential lack of blinding. |
Low risk of bias |
Data from full clinical study report. Only one measurement and result provided for the time point selected by review authors. |
Low risk of bias |
No risk of bias identified. |
