3. Detailed risk of bias and applicability assessment.
| Study | ||||||||||||||
| Backs‐Dermott 2010 | Berlanga 1999 | Johansson 2015 | Judd 2016 | Klein 2018 | Pintor 2009 | Ruhe 2019 | Van Loo 2015 | Van Loo 2018 | Van Loo 2020 | Wang 2014 | ||||
| Type of study | Development | Development | Development | Development | Development | Validation | Development | Development | Development | Validation | Development | Validation | Development | Validation |
| Domain 1: Participants | ||||||||||||||
| A. Risk of bias | ||||||||||||||
| 1.1. Appropriate data sources? | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| 1.2. Appropriate inclusions and exclusion? | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Risk of bias | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low |
| B. Applicability | ||||||||||||||
| Concern about applicability | Low | Unclear | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low |
| Domain 2: Predictors | ||||||||||||||
| A. Risk of bias | ||||||||||||||
| 2.1. Defined and assessed in similar way for all participants? | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| 2.2. Assessments made without knowledge of outcome? | Probably yes | Probably yes | Yes | Yes | Yes | Yes | No information | Yes | Probably yes | Probably yes | No information | No information | Probably yes | Probably yes |
| 2.3. All available at time of model’s intended use? | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | No | Yes | Yes |
| Risk of bias | Low | Low | Low | Low | Low | Low | Unclear | Low | Low | Low | Unclear | High | Low | Low |
| B. Applicability | ||||||||||||||
| Concern about applicability | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low |
| Domain 3: Outcome | ||||||||||||||
| A. Risk of bias | ||||||||||||||
| 3.1. Determined appropriately? | Yes | Yes | Yes | Probably yes | Yes | Yes | No information | Yes | Yes | Yes | Yes | Yes | Probably yes | Probably yes |
| 3.2. Pre‐specified or standard definition? | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| 3.3. Predictors excluded from outcome definition? | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| 3.4. Defined and determined similar for all participants? | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| 3.5. Determined without knowledge of predictors? | No information | No information | No information | Probably yes | Yes | Yes | No information | No information | No information | No information | No information | No information | No information | No information |
| 3.6. Appropriate time interval between predictor assessment and outcome determination? | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
| Risk of bias | Unclear | Unclear | Unclear | Low | Low | Low | Unclear | Unclear | Unclear | Unclear | Unclear | Unclear | Unclear | Unclear |
| B. Applicability | ||||||||||||||
| Concern about applicability | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low |
| Domain 4: Analysis | ||||||||||||||
| 4.1. Reasonable number of participants with outcome? | Probably yes | No | No | No | Probably yes | Yes | No | No | No | No | No | Probably yes | No information | Yes |
| 4.2. Predictors handled appropriately? | Yes | Probably yes | Yes | No | Probably yes | Probably yes | No | Probably no | No | No | Probably yes | Probably yes | No | No |
| 4.3. All enrolled participants included in analysis? | No | No | Yes | No | Yes | Yes | Yes | No | Probably yes | Probably yes | No | Yes | Yes | Yes |
| 4.4. Missing data handled appropriately? | No information | No information | No information | Yes | Yes | Yes | No information | No | No | No | Yes | Yes | Probably no | Probably no |
| 4.5. Univariable analysis avoided? | No | No | No | No | Yes | NA | No | Yes | Yes | NA | Yes | NA | No | NA |
| 4.6. Complexities in data accounted for? | Probably yes | Probably yes | Probably yes | Yes | Yes | Yes | Probably yes | Yes | Probably yes | Probably yes | Yes | Probably yes | Probably yes | Probably yes |
| 4.7. Relevant performance measures? | No | No | No | No | Yes | Yes | No | No | No | No | No | No | No | No |
| 4.8. Overfitting and optimism accounted for? | No | No | No | No | Yes | NA | No | No | Yes | NA | Yes | NA | Yes | NA |
| 4.9. Final model corresponds to multivariable analysis? | No information | No information | Probably yes | No information | Yes | NA | No information | No information | Probably no | NA | Probably yes | NA | No information | NA |
| Risk of bias | High | High | High | High | Low | Low | High | High | High | High | High | High | High | High |
| Overall assessment of risk of bias | High | High | High | High | Low | Low | High | High | High | High | High | High | High | High |
| Overall concern for applicability | Low | Unclear | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low | Low |
Validation refers to external validation