| Background/relevance: 3 items (1 primary, 2 secondary) |
| Primary | 1. Clear underlying hypotheses and specific research questions | | |
| Secondary | 2. Relevant population and setting | | |
| Secondary | 3. Relevant interventions and outcomes are included | | |
| Design 4 items: (2 primary, 2 secondary) |
| Primary | 1. Evidence of a priori protocol, review of analyses, statistical analysis plan, and interpretation of results | | |
| Primary | 2. Comparison groups justified | | |
| Secondary | 3. Registration in a public repository with commitment to publish results | | |
| Secondary | 4. Data sources that are sufficient to support the studya | | |
| Measures: 4 items (2 primary, 2 secondary) |
| Primary | 1. Was exposure clearly defined, measured and (relevance) justifiedb | | |
| Primary | 2. Primary outcomes defined, measured and (relevance) justifiedb | | |
| Secondary | 3. Length of observation: Sufficient follow up duration to reliably assess outcomes of interest and long-term treatment effects | | |
| Secondary | 4. Sample size: calculated based on clear a priori hypotheses regarding the occurrence of outcomes of interest and target effect of studied treatment versus comparator | | |
| Analyses 3 items (1 primary, 2 secondary) |
| Primary | 1. Thorough assessment of and mitigation strategy for potential confounders | | |
| Secondary | 2. Study groups are compared at baseline and analyses of subgroups or interaction effects reported | | |
| Secondary | 3. Sensitivity analyses are performed to check the robustness of results and the effects of key assumptions on definitions or outcomes | | |
| Results/reporting: 6 items (2 primary, 4 secondary) |
| Primary | 1. Extensive presentation of results/authors describe the key components of their statistical approachesa | | |
| Primary | 2. Were confounder-adjusted estimates of treatment effects reportedb | | |
| Secondary | 3. Flow chart explaining all exclusions and individuals screened or selected at each stage of defining the final sample | | |
| Secondary | 4. Was follow-up similar or accounted for between groups | | |
| Secondary | 5. Did the authors describe the statistical uncertainty of their findings | | |
| Secondary | 6. Was the extent of missing data reported | | |
| Discussion/interpretation: 4 items (2 primary, 2 Secondary) |
| Primary | 1. Results consistent with known information or if not, was an explanation provided | | |
| Primary | 2. Are the observed treatment effects considered clinically meaningful | | |
| Secondary | 3. Discussion of possible biases and confounding factors, especially related to the observational nature of the study | | |
| Secondary | 4. Suggestions for future research to challenge, strengthen, or extend the study results | | |
| Conflict of interest: (1 primary item) |
| Primary | 1. Potential conflicts of interest, including study funding, were stated | | |
