medsci-skills 4.1.0

package/skills/check-reporting/references/checklists/ROBINS_E.md

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+# ROBINS-E Assessment Guide
+
+Risk Of Bias In Non-randomized Studies — of Exposures.
+Reference: Higgins JPT et al. Environment International 2024;186:108602. doi: 10.1016/j.envint.2024.108602.
+Website: https://www.riskofbias.info/welcome/robins-e-tool
+
+## Purpose
+
+ROBINS-E assesses the risk of **material bias** in individual observational studies examining the effect of an **exposure** on an outcome. Designed for follow-up (cohort) studies. Material bias = bias sufficient to affect the direction of the estimated effect or impact the ability to draw conclusions.
+
+## Structure
+
+ROBINS-E has:
+- **Planning stage**: List confounders and consider appropriateness
+- **Preliminary considerations** (per study): Sections A-E
+- **7 bias domains** with signalling questions
+- **Overall judgment** across domains
+
+Signalling question responses: Yes / Probably yes / Probably no / No / No information
+(Some questions have domain-specific response options)
+
+Domain judgments: Low risk of bias / Some concerns / High risk of bias / Very high risk of bias
+
+Three outputs per domain:
+1. Risk of bias judgment (algorithmic, overridable)
+2. Predicted direction of bias
+3. Whether bias threatens conclusions (Yes / No / Cannot tell)
+
+## Planning Stage
+
+### P1: List Important Confounding Factors
+Specify confounders relevant to all or most studies on this topic. State whether they are particular to specific exposure-outcome combinations.
+
+### P2: Appropriateness Assessment
+Will the review use the ROBINS-E assessment of appropriateness (study sensitivity)? → Yes / No
+If Yes, complete Appendix 1 (Parts I, II, III).
+
+## Preliminary Considerations (Per Study)
+
+### A. Specify the Result Being Assessed
+- ROBINS-E is specific to a particular study result
+- Different results from the same study may have different risks of bias
+- Specify the numerical result (e.g., RR=1.52, 95% CI 0.83 to 2.77)
+
+### B. Decide Whether to Proceed
+- Some study characteristics may directly indicate very high risk of bias
+- Screening section to identify such situations before detailed assessment
+
+### C. Specify the Analysis
+- Gather information about participants, exposure measure(s), outcome, and analysis methods
+
+### D. Specify the Causal Effect
+- Define the causal effect of exposure being estimated
+- This is essential: the causal effect defines what the result would be in the absence of bias
+
+### E. Evaluation of Confounding Factors
+- Identify which important confounders (from P1) are controlled for in the analysis
+- Assess whether control is adequate
+
+## Domain 1: Risk of Bias Due to Confounding
+
+### Key Signalling Questions
+- Were all important confounding domains measured?
+- Were all important confounding domains adequately controlled for?
+- Was the analysis adjusted for all important confounders, or was matching/restriction used?
+- Were appropriate methods used to control confounding (regression, propensity score, IP weighting)?
+
+### Judgment
+- **Low risk of bias (except for concerns about uncontrolled confounding)**: All critical confounders well addressed, but residual uncontrolled confounding cannot be eliminated in observational studies
+- **Some concerns**: Minor concerns about residual confounding
+- **High risk of bias**: Important confounders not adequately controlled
+- **Very high risk of bias**: Critical confounding renders the estimate unreliable
+
+*Note: For Domain 1, 'Low risk' is expressed as "Low risk of bias (except for concerns about uncontrolled confounding)" because uncontrolled confounding can never be fully excluded in observational studies.*
+
+## Domain 2: Risk of Bias Arising from Measurement of the Exposure
+
+### Key Signalling Questions
+- Was the exposure clearly defined and consistently measured?
+- Was exposure assessment valid and reliable?
+- Was exposure measured at the appropriate time point?
+- Was exposure classification differential with respect to the outcome?
+
+### Judgment
+- **Low**: Exposure well-defined, measured validly, non-differential misclassification
+- **Some concerns**: Minor measurement issues unlikely to materially affect results
+- **High**: Exposure measurement likely to introduce material bias
+- **Very high**: Exposure so poorly measured that no useful estimate possible
+
+## Domain 3: Risk of Bias in Selection of Participants
+
+### Key Signalling Questions
+- Was selection into the study (or into the analysis) related to both exposure and outcome?
+- Was start of follow-up aligned with exposure assessment?
+- Were adjustments made for selection effects?
+
+### Judgment
+- **Low**: Selection not related to both exposure and outcome
+- **Some concerns**: Minor selection issues
+- **High**: Selection bias likely to materially affect results
+- **Very high**: Extreme selection bias
+
+## Domain 4: Risk of Bias Due to Post-exposure Interventions
+
+### Key Signalling Questions
+- Were there post-exposure interventions that could have affected the outcome?
+- Were these interventions differential across exposure groups?
+- Were they likely to affect the estimated exposure effect?
+
+### Judgment
+- **Low**: No important post-exposure interventions, or balanced across groups
+- **Some concerns**: Some differential post-exposure interventions
+- **High**: Important post-exposure interventions likely bias the result
+- **Very high**: Post-exposure interventions dominate the observed effect
+
+## Domain 5: Risk of Bias Due to Missing Data
+
+### Key Signalling Questions
+- Were outcome data available for all or nearly all participants?
+- Were participants excluded due to missing data on exposure or other variables?
+- Was the proportion of missing data similar across exposure groups?
+- Were appropriate methods used to handle missing data?
+
+### Judgment
+- **Low**: Complete data or minimal, non-differential missingness
+- **Some concerns**: Some missing data but unlikely to materially bias results
+- **High**: Missing data pattern likely to introduce material bias
+- **Very high**: Extensive missing data with differential patterns
+
+## Domain 6: Risk of Bias Arising from Measurement of the Outcome
+
+### Key Signalling Questions
+- Could outcome measurement have been influenced by knowledge of exposure status?
+- Were outcome assessors blinded to exposure?
+- Were outcome measures comparable across exposure groups?
+- Was the outcome defined and assessed using validated methods?
+
+### Judgment
+- **Low**: Objective outcome or blinded assessment, non-differential measurement
+- **Some concerns**: Minor measurement concerns
+- **High**: Outcome measurement likely differentially affected by exposure knowledge
+- **Very high**: Outcome measurement severely compromised
+
+## Domain 7: Risk of Bias in Selection of the Reported Result
+
+### Key Signalling Questions
+- Were multiple outcome measurements reported?
+- Were multiple analyses performed (different adjustments, subgroups, models)?
+- Is the reported result likely selected from among multiple measurements or analyses?
+
+### Judgment
+- **Low**: Pre-specified analysis plan or single planned analysis
+- **Some concerns**: Minor concerns about selective reporting
+- **High**: Reported result likely selected to favor a particular conclusion
+- **Very high**: Clear evidence of selective reporting
+
+## Overall Risk of Bias
+
+Three overall judgments are derived from the domain judgments:
+
+1. **Overall risk of bias**: Most conservative across domains
+   - **Low**: Low in all domains
+   - **Some concerns**: Some concerns in at least one domain, but no high/very high
+   - **High**: High in at least one domain, but not very high in any
+   - **Very high**: Very high in at least one domain
+
+2. **Overall predicted direction of bias**: Considering all domains together
+
+3. **Overall: does bias threaten conclusions?**: Yes / No / Cannot tell
+
+Justification should be provided when overriding algorithm-suggested judgments.
+
+## When to Use
+
+- Systematic reviews of observational studies examining exposure effects (environmental, occupational, behavioral, dietary)
+- Currently designed for cohort (follow-up) studies
+- Not for case-control studies (extension planned)
+- Not for intervention studies (use ROBINS-I instead)
+- Complementary to GRADE for rating certainty of evidence from observational studies

package/skills/check-reporting/references/checklists/ROBINS_I.md

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+# ROBINS-I Assessment Guide
+
+Risk Of Bias In Non-randomised Studies - of Interventions.
+Reference: Sterne JAC et al. BMJ 2016;355:i4919.
+
+## Structure
+
+ROBINS-I assesses 7 domains + overall judgment.
+- **Signalling questions**: Yes / Probably yes / Probably no / No / No information
+- **Domain judgment**: Low / Moderate / Serious / Critical / No information
+- **Overall judgment**: Lowest of all domain judgments (most conservative)
+
+## Pre-assessment Requirements
+
+Before applying ROBINS-I, specify:
+1. The target trial (what RCT would ideally answer this question?)
+2. The effect of interest (assignment to intervention vs starting and adhering)
+3. Confounders to be controlled
+
+## Domain 1: Bias Due to Confounding
+
+### Key Questions
+- Is there potential for confounding not accounted for?
+- Did the authors use appropriate methods to control confounding (matching, regression, propensity score)?
+
+### Judgment
+- **Low**: All critical confounders appropriately controlled
+- **Moderate**: Minor concerns about residual confounding
+- **Serious**: Important confounders not adequately controlled
+- **Critical**: Confounding so severe that no useful estimate possible
+
+## Domain 2: Bias in Selection of Participants
+
+### Key Questions
+- Was selection into the study related to both intervention and outcome?
+- Was start of follow-up and intervention aligned?
+- Were adjustments made for different start times?
+
+## Domain 3: Bias in Classification of Interventions
+
+### Key Questions
+- Were intervention groups clearly defined?
+- Was information used to classify interventions recorded at the start of the intervention?
+- Could classification of intervention status have been affected by knowledge of the outcome?
+
+## Domain 4: Bias Due to Deviations from Intended Interventions
+
+### Key Questions
+- Were there deviations from intended intervention beyond what would be expected?
+- Were these deviations unbalanced between groups and likely to affect outcomes?
+- Were important co-interventions balanced across groups?
+
+## Domain 5: Bias Due to Missing Data
+
+### Key Questions
+- Were outcome data available for all or nearly all participants?
+- Were participants excluded due to missing data on intervention or other variables?
+- Was the proportion of missing data similar across groups?
+- Were appropriate methods used to handle missing data?
+
+## Domain 6: Bias in Measurement of Outcomes
+
+### Key Questions
+- Could outcome measurement have been influenced by knowledge of intervention?
+- Were outcome assessors blinded?
+- Were outcome measures comparable across groups?
+
+## Domain 7: Bias in Selection of Reported Result
+
+### Key Questions
+- Were multiple outcome measurements reported?
+- Were multiple analyses performed?
+- Is the reported result likely selected from among multiple measurements or analyses?
+
+## Overall Risk of Bias
+
+The overall judgment is the most conservative across all domains:
+- **Low**: Low risk in all domains
+- **Moderate**: Low or moderate in all domains
+- **Serious**: Serious in at least one domain, but not critical in any
+- **Critical**: Critical in at least one domain
+
+## Recommendation for Synthesis
+
+- Studies at **critical** risk of bias should be excluded from meta-analysis
+- Present critical studies in a separate table for completeness
+- Conduct sensitivity analysis excluding serious risk of bias studies

package/skills/check-reporting/references/checklists/ROBIS.md

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+# ROBIS Assessment Guide
+
+Risk Of Bias In Systematic Reviews, version 1.2.
+Reference: Whiting P et al. J Clin Epidemiol 2016;69:225-234.
+
+## Purpose
+
+ROBIS assesses the risk of bias **in systematic reviews themselves** (not in individual studies). It evaluates whether the review process was conducted appropriately and whether the conclusions are trustworthy.
+
+Applicable to reviews of: interventions, aetiology, diagnosis, and prognosis.
+
+## Structure
+
+ROBIS has 3 phases:
+- **Phase 1** (optional): Assessing relevance of the review to the target question
+- **Phase 2**: Identifying concerns with the review process (4 domains, signalling questions)
+- **Phase 3**: Judging overall risk of bias in the review
+
+Signalling questions answered: Y (Yes) / PY (Probably Yes) / PN (Probably No) / N (No) / NI (No Information)
+
+Domain concerns rated: LOW / HIGH / UNCLEAR
+
+## Phase 1: Assessing Relevance (Optional)
+
+State the target question and compare it with the question addressed by the review.
+
+For **intervention reviews**, specify: Patients/Population, Intervention(s), Comparator(s), Outcome(s)
+
+For **aetiology reviews**, specify: Patients/Population, Exposure(s) and Comparator(s), Outcome(s)
+
+For **DTA reviews**, specify: Patients, Index test(s), Reference standard, Target condition
+
+For **prognostic reviews**, specify: Patients, Outcome to be predicted, Intended use of model, Intended moment in time
+
+Final question: Does the question addressed by the review match the target question? → YES / NO / UNCLEAR
+
+## Phase 2: Identifying Concerns with the Review Process
+
+### Domain 1: Study Eligibility Criteria
+
+Describe the study eligibility criteria, any restrictions, and whether objectives and criteria were pre-specified.
+
+#### Signalling Questions
+1.1 Did the review adhere to pre-defined objectives and eligibility criteria?
+1.2 Were the eligibility criteria appropriate for the review question?
+1.3 Were eligibility criteria unambiguous?
+1.4 Were any restrictions in eligibility criteria based on study characteristics appropriate (e.g., date, sample size, study quality, outcomes measured)?
+1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g., publication status or format, language, availability of data)?
+
+**Concerns regarding specification of study eligibility criteria:** LOW / HIGH / UNCLEAR
+
+### Domain 2: Identification and Selection of Studies
+
+Describe methods of study identification and selection (e.g., number of reviewers involved).
+
+#### Signalling Questions
+2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports?
+2.2 Were methods additional to database searching used to identify relevant reports?
+2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible?
+2.4 Were restrictions based on date, publication format, or language appropriate?
+2.5 Were efforts made to minimise error in selection of studies?
+
+**Concerns regarding methods used to identify and/or select studies:** LOW / HIGH / UNCLEAR
+
+### Domain 3: Data Collection and Study Appraisal
+
+Describe methods of data collection, what data were extracted, how risk of bias was assessed (e.g., number of reviewers), and the tool used.
+
+#### Signalling Questions
+3.1 Were efforts made to minimise error in data collection?
+3.2 Were sufficient study characteristics available for both review authors and readers to be able to interpret the results?
+3.3 Were all relevant study results collected for use in the synthesis?
+3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria?
+3.5 Were efforts made to minimise error in risk of bias assessment?
+
+**Concerns regarding methods used to collect data and appraise studies:** LOW / HIGH / UNCLEAR
+
+### Domain 4: Synthesis and Findings
+
+Describe synthesis methods.
+
+#### Signalling Questions
+4.1 Did the synthesis include all studies that it should?
+4.2 Were all pre-defined analyses reported or departures explained?
+4.3 Was the synthesis appropriate given the nature and similarity in the research questions, study designs and outcomes across included studies?
+4.4 Was between-study variation (heterogeneity) minimal or addressed in the synthesis?
+4.5 Were the findings robust e.g. as demonstrated through funnel plot or sensitivity analyses?
+4.6 Were biases in primary studies minimal or addressed in the synthesis?
+
+**Concerns regarding the synthesis and findings:** LOW / HIGH / UNCLEAR
+
+## Phase 3: Judging Risk of Bias in the Review
+
+Describe whether conclusions were supported by the evidence.
+
+### Signalling Questions
+A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4?
+B. Was the relevance of identified studies to the review's research question appropriately considered?
+C. Did the reviewers avoid emphasizing results on the basis of their statistical significance?
+
+**Risk of bias in the review:** LOW / HIGH / UNCLEAR
+
+### Judgment Algorithm
+- **Low risk**: Concerns are low across all domains and Phase 3 questions are favorable
+- **High risk**: High concerns in one or more domains, or the interpretation does not adequately address identified concerns
+- **Unclear**: Insufficient information to make a judgment
+
+## When to Use
+
+- Assessing quality of existing systematic reviews (overview of reviews)
+- Evaluating competing systematic reviews on the same topic
+- Guideline development (appraising evidence base)
+- Critical appraisal teaching and journal clubs
+- Not for assessing individual primary studies (use QUADAS-2, RoB 2, ROBINS-I, etc.)

package/skills/check-reporting/references/checklists/ROB_ME.md

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+# ROB-ME Assessment Guide
+
+Risk Of Bias due to Missing Evidence in a meta-analysis.
+Reference: Page MJ et al. BMJ 2023;383:e076"; ROB-ME Cribsheet Version 1, October 2023.
+Website: https://www.riskofbias.info/welcome/rob-me-tool
+
+## Purpose
+
+ROB-ME assesses the risk of bias in a **pairwise meta-analysis result** due to missing evidence — encompassing both non-reporting biases (selective reporting of results) and non-publication biases (unpublished studies). It is applied at the synthesis level (not individual study level).
+
+## Structure
+
+ROB-ME has 5 steps applied to **each meta-analysis** in a systematic review:
+1. Select and define meta-analyses to assess
+2. Determine which studies have missing results (Results Matrix)
+3. Consider the potential for missing studies across the systematic review
+4. Assess risk of bias due to missing evidence (signalling questions)
+5. Overall risk of bias judgment
+
+Response options: Y (Yes) / PY (Probably Yes) / PN (Probably No) / N (No) / NI (No Information) / NA (Not Applicable)
+
+Green-underlined responses are potential markers for **low** risk of bias.
+Red responses are potential markers for **a** risk of bias.
+
+## Step 1: Select and Define Meta-analyses
+
+For each meta-analysis, specify:
+- The PICO: Participants, Intervention, Comparator, Outcome
+- Eligible study designs
+- Eligible outcome definitions (measures, metrics, time points)
+- Eligible methods of analysis (analysis populations, crude vs adjusted estimates)
+
+## Step 2: Determine Which Studies Have Missing Results (Results Matrix)
+
+For each study meeting inclusion criteria, create a Results Matrix using these symbols:
+
+| Symbol | Meaning |
+|--------|---------|
+| check (green) | A study result is available for inclusion in the meta-analysis |
+| ~ (yellow) | No study result available, for a reason **unrelated** to the P value, magnitude or direction |
+| ? (orange) | Unclear whether an eligible result was generated |
+| X (red) | No study result available, **likely because of** the P value, magnitude or direction |
+
+Record: Study ID, Source(s) used, Number of participants analysed, and availability status for each meta-analysis.
+
+Also record any known information about the results (direction of effect, statistical significance, or narrative descriptions).
+
+## Step 3: Consider the Potential for Missing Studies
+
+Answer the following questions **once** for the systematic review as a whole:
+
+### Signalling Questions
+3.1 Were prospectively registered studies or studies identified for a prospective meta-analysis the only type of study eligible for inclusion?
+   - **Y**: inception cohort → lower risk of missing studies
+   - **N**: proceed to 3.2
+
+3.2 If N to 3.1: Would you expect every eligible study to be identifiable regardless of its results?
+   - **NA/Y/PY**: lower risk
+   - **PN/N**: higher risk — proceed to 3.3
+
+3.3 If Y/PY to 3.2: Were you likely to have found all eligible studies regardless of their results?
+   - Consider: trial registers searched, search strategy designed to retrieve regardless of outcomes
+   - **NA/Y/PY**: lower risk
+   - **PN/N**: higher risk — check the box indicating potential for missing studies
+
+## Step 4: Assess Risk of Bias (per meta-analysis)
+
+Specify the meta-analysis details: description, summary effect estimate (95% CI), number of included studies and participants.
+
+### Within-study Assessment ('Known Unknowns')
+
+4.1 Of the studies identified, was there any for which no result was available for inclusion in the meta-analysis, **likely because of the P value, magnitude or direction** of the result generated (refer to Step 2)?
+   - Answer 'Yes' if any study has an 'X' in the Results Matrix for this meta-analysis
+   - **Y/N**
+
+4.2 If Y to 4.1: Is it likely that there would be a notable change to the summary effect estimate if the omitted results had been included?
+   - Consider: amount of missing evidence relative to total; direction of effect in omitted studies; fixed-effect vs random-effects model
+   - **Trivial missing → 'No/Probably no'**; Non-trivial with differing direction → 'Yes/Probably yes'
+   - **NA/Y/PY/PN/N/NI**
+
+### Within-study Assessment ('Unknown Unknowns')
+
+4.3 Of the studies identified, was there any for which it was unclear whether an eligible result was generated (refer to Step 2)?
+   - Answer 'Yes' if any study has a '?' in the Results Matrix
+   - **Y/N**
+
+4.4 If Y to 4.3: Is it likely that there would be a notable change to the summary effect estimate if the potentially omitted results had been included?
+   - Consider same factors as 4.2 but for 'potentially' missing evidence
+   - **NA/Y/PY/PN/N/NI**
+
+### Across-study Assessment
+
+4.5 Do circumstances (identified in Step 3) indicate potential for some eligible studies not being identified because of the P value, magnitude or direction of the results generated?
+   - Answer 'Yes' if the checkbox in Step 3 was checked
+   - **Y/N**
+
+4.6 If Y to 4.5: Is it likely that studies not identified had results that were eligible for inclusion in the meta-analysis?
+   - Consider: core outcome sets, scope of outcome domain, whether missing studies would have measured this outcome
+   - **NA/Y/PY/PN/N**
+
+4.7 If Y to 4.1, 4.3, or 4.5: Does the pattern of observed study results suggest that the meta-analysis is likely to be missing results that were systematically different (in terms of P value, magnitude or direction) from those observed?
+   - Methods: (1) funnel plot inspection, (2) funnel plot asymmetry test, (3) compare fixed-effect vs random-effects estimates, (4) inspect P values/direction in forest plot
+   - Distinguish small-study effects from non-reporting biases
+   - **NA/Y/PY/PN/N**
+
+4.8 If Y/PY/NI to 4.2, 4.4, 4.6, or 4.7: Did sensitivity analyses suggest that the summary effect estimate was biased due to missing results?
+   - Consider: selection models, regression-based adjustment, restricting to largest studies
+   - **NA/Y/PY/PN/N**
+
+## Step 5: Risk of Bias Judgment
+
+### Judgment Scale
+- **Low**: Little or no concern about missing evidence biasing the meta-analysis result
+- **Some concerns**: Some concern but not sufficient to judge high risk
+- **High**: The meta-analysis result is likely biased due to missing evidence
+
+### Optional: Predicted Direction of Bias
+- Favours experimental / Favours comparator / Towards null / Away from null / Unpredictable
+
+## When to Use
+
+- Every pairwise meta-analysis in a systematic review (PRISMA 2020 recommends this)
+- Replaces informal funnel plot interpretation with a structured assessment
+- Complements individual study RoB tools (RoB 2, ROBINS-I, QUADAS-2)
+- Not designed for network meta-analysis (use RoB NMA instead)
+- Should be completed by someone familiar with the meta-analysis methods and included studies

package/skills/check-reporting/references/checklists/RoB2.md

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+# RoB 2 Assessment Guide
+
+Revised Cochrane Risk-of-Bias tool for Randomised Trials.
+Reference: Sterne JAC et al. BMJ 2019;366:l4898. PMID: 31462531.
+
+## Structure
+
+RoB 2 assesses 5 domains for each outcome in each study.
+- **Signalling questions**: Yes / Probably yes / Probably no / No / No information
+- **Domain judgment**: Low risk / Some concerns / High risk
+- **Overall judgment**: Most conservative across all domains
+
+## Domain 1: Bias Arising from the Randomisation Process
+
+### Signalling Questions
+1. Was the allocation sequence random?
+2. Was the allocation sequence concealed until participants were enrolled and assigned?
+3. Did baseline differences between groups suggest a problem with the randomisation process?
+
+### Judgment
+- **Low**: Adequate random sequence generation AND allocation concealment, no problematic baseline imbalances
+- **Some concerns**: Information insufficient to permit judgment
+- **High**: Inadequate sequence generation or concealment, or problematic baseline imbalances suggest failure
+
+## Domain 2: Bias Due to Deviations from Intended Interventions
+
+### Effect of Interest: Assignment (intention-to-treat)
+1. Were participants aware of their assigned intervention during the trial?
+2. Were carers and people delivering the interventions aware of assigned intervention?
+3. Were there deviations from the intended intervention that arose because of the trial context?
+4. Were these deviations likely to have affected the outcome?
+5. Was an appropriate analysis used to estimate the effect of assignment to intervention?
+
+### Effect of Interest: Adherence (per-protocol)
+1-2. Same as above
+3. Were important non-protocol interventions balanced across groups?
+4. Could failures in implementing the intervention have affected the outcome?
+5. Did trial participants adhere to the assigned intervention regimen?
+6. Was an appropriate analysis used to estimate the effect of adhering to intervention?
+
+## Domain 3: Bias Due to Missing Outcome Data
+
+### Signalling Questions
+1. Were data for this outcome available for all, or nearly all, participants randomised?
+2. Is there evidence that the result was not biased by missing outcome data?
+3. Could missingness in the outcome depend on its true value?
+4. Is it likely that missingness depended on its true value?
+
+### Judgment
+- **Low**: Data available for all/nearly all (>95%), or evidence result not biased by missing data
+- **Some concerns**: Missingness could depend on true value but unlikely
+- **High**: Missingness likely dependent on true value
+
+## Domain 4: Bias in Measurement of the Outcome
+
+### Signalling Questions
+1. Was the method of measuring the outcome inappropriate?
+2. Could measurement or ascertainment of the outcome have differed between groups?
+3. Were outcome assessors aware of the intervention received by study participants?
+4. Could assessment of the outcome have been influenced by knowledge of intervention?
+5. Is it likely that assessment was influenced by knowledge of intervention?
+
+## Domain 5: Bias in Selection of the Reported Result
+
+### Signalling Questions
+1. Were the data that produced this result analysed in accordance with a pre-specified analysis plan finalised before unblinded outcome data were available?
+2. Is the numerical result likely to have been selected from multiple eligible outcome measurements or analyses of the data?
+
+## Overall Risk of Bias
+
+- **Low risk**: Low risk in all domains
+- **Some concerns**: Some concerns in at least one domain, but not high risk in any
+- **High risk**: High risk in at least one domain, OR some concerns in multiple domains in a way that substantially lowers confidence
+
+## When to Use
+
+- Use for **individually randomised, parallel-group trials** (default)
+- Variants available for: cluster-randomised trials, crossover trials
+- Do NOT use for non-randomised studies (use ROBINS-I instead)