# Evidence sheet: liberal transfusion thresholds × overall 180-day neurologic outcome in acute brain injury

Verdict 2932 · Evidence Check

Stored-material review date: Not recorded  
Original evidence cut-off: 2026-08-26  
Review-criteria version: 1.0  
Public page/material preparation date: 2026-10-10

Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect.

## Assessment scope

- Population: TRAIN's anemic mixed TBI/SAH/ICH population; HEMOTION's traumatic-injury-only population; not extended to effects in every patient or subgroup
- Ingredient, formulation and route: Historical assigned strategies of 9 versus 7 g/dL in TRAIN and 10 versus 7 g/dL in HEMOTION; not transfusion, threshold or suitability recommendations
- Dose: Not recorded
- Comparator: Each trial's liberal/restrictive thresholds and actual transfusion/concomitant treatment; causes of population/threshold differences remain unverified
- Measured outcome: TRAIN's unfavorable GOS-E 1~5 at 180 days and HEMOTION's unfavorable outcome at six months; different definitions, denominators and estimates
- Duration: Each 180-day/six-month assessment specification; not extended to other durations or lifelong outcomes
- Questions outside this scope: Certifying TRAIN's overall result as equal effects across all brain injuries, anemia levels, individuals or each TBI/SAH/ICH subgroup; Repurposing HEMOTION's traumatic-injury 10-versus-7 strategy as identical direct replication of TRAIN's mixed-population 9-versus-7 strategy or hemorrhage subgroups; Calculating new exclusion/missingness counts or rates, total participants or events from 850/806/393/413, 742/722 or safety denominators 397/423; Copying TRAIN's GOS-E 1~5 as HEMOTION's exact cutoff/baseline-specific adjudication, or equating 180-day and six-month windows without verification; Converting original unfavorable-outcome rates into favorable-outcome rates or individual probabilities, or recalculating/reversing signs/reciprocals/new RRs for difference −10.0/RR .86 or difference 5.4/CI; Repurposing original positive/null or opposing-conclusion wording as reversed effect signs, proven interaction under identical conditions, zero HEMOTION effect, equivalence or exclusion of important effects; Presenting population/threshold differences alone as proof of conflict causes or effect modification; Changing original Korean core-summary size wording/English differences into new trial-size judgments or corrections, or deleting current numbers/history; Repurposing transfusion medians of 2/0 as total exposure, every individual's exposure or a new dose-response effect; Changing safety cerebral ischemia of 35/397 versus 57/423 and RR .65/CI into primary-outcome denominators, overall safety, zero other harm or individual suitability; Changing public/nonprofit funding or CIHR 'and others' into absence of all product/company/staff/COI involvement or certified independence; Extending research thresholds, blood exposure or 180-day outcomes into transfusion/threshold/individual-suitability, treatment-administration or replacement guidance; Adding the same reports/trials/populations or different questions/groups/timepoints/denominators as new independent trials or total participants; Inheriting parent scores/axes, historical cross-checks, registration matches or full-text review accounts as subclaim values, current content review or external reading; New search/API use, numerical calculations, hypothetical numbers, new effects/CIs/grades, independent certification or treatment/suitability/administration guidance

## Checklist items

### N01 · What are the existing subclaim and parent values for the overall acute-brain-injury question?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: The selected existing question is improved 180-day neurologic outcome across acute brain injury. Its C grade and note describe positive TRAIN and null HEMOTION findings as conflicting. Subclaim score, status and axes are absent; parent C56, Caution and H/R0/I2/E+/B1 remain parent context.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Absent subclaim values are not filled with parent scores or axes, and no new grade is created. Existing content review remains incomplete.
- Reason for missing information: Absent subclaim values are not filled with parent scores or axes, and no new grade is created.
- Required materials and conditions: Separate the subclaim C grade and note, absent score/status/axes, and parent C56/axes
- Materials to obtain first: Additional materials for the selected question or user feedback
- Further research: Proposal: Record separate sources for the overall question and original verdict. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Separate the subclaim C grade and note, absent score/status/axes, and parent C56/axes must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Separate the subclaim C grade and note, absent score/status/axes, and parent C56/axes to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design
- Related sources: S01, S02

### N02 · Which brain-injury populations does TRAIN's overall population include?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN studied anemic acute brain injury including traumatic brain injury, subarachnoid hemorrhage and intracerebral hemorrhage, randomizing 850 participants across 72 ICUs in 22 countries. This is not extended to universal effects across all brain injuries, anemia levels or treatment settings.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Exact stage/severity, age, anemia and eligibility criteria, and baseline characteristics and denominators by injury remain unverified. Existing content review remains incomplete.
- Reason for missing information: Exact stage/severity, age, anemia and eligibility criteria, and baseline characteristics and denominators by injury remain unverified.
- Required materials and conditions: Anemia, TBI/SAH/ICH, 22 countries and 72 ICUs, and eligibility scope
- Materials to obtain first: Eligibility/exclusions, baseline and injury-specific tables, and recruitment materials
- Further research: Proposal: Link materials on the mixed overall population and eligibility conditions. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Anemia, TBI/SAH/ICH, 22 countries and 72 ICUs, and eligibility scope must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Anemia, TBI/SAH/ICH, 22 countries and 72 ICUs, and eligibility scope to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.1; detailed population conditions are Chamgap's own design
- Related sources: S01

### N03 · What historical trial strategy does the 9 versus 7 g/dL comparison represent?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN's 9 versus 7 g/dL thresholds are historical trial conditions. Assigned liberal/restrictive strategies are distinguished from actual transfusion volume/timing and individual suitability; no transfusion, threshold or treatment instructions are created.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Actual threshold adherence, crossover/deviations, blood exposure/timing and concomitant treatment details remain unverified. Existing content review remains incomplete.
- Reason for missing information: Actual threshold adherence, crossover/deviations, blood exposure/timing and concomitant treatment details remain unverified.
- Required materials and conditions: Separate assigned thresholds, actual exposure, and baseline/concomitant treatment
- Materials to obtain first: Actual transfusion, adherence and concomitant treatment records, and protocol
- Further research: Proposal: Link assigned strategies and actual exposure. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Separate assigned thresholds, actual exposure, and baseline/concomitant treatment must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Separate assigned thresholds, actual exposure, and baseline/concomitant treatment to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.2–3.2.3; Reverse-direction labels and assessment adaptation are Chamgap design; M03 §3.2.3 and M08 §8.2.2–8.2.3; Chamgap application
- Related sources: S01

### N04 · What is known about allocation and assessment in the open-label randomized design?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN was a multinational open-label randomized trial. Open treatment and masking/measurement of the 180-day neurologic assessor are kept separate; the original H/B1 axes do not establish actual assessor blinding.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Allocation generation/concealment, assessor/patient awareness and assessment conditions remain unverified. Existing content review remains incomplete.
- Reason for missing information: Allocation generation/concealment, assessor/patient awareness and assessment conditions remain unverified.
- Required materials and conditions: Allocation generation/concealment, open-label status, and 180-day assessment/masking
- Materials to obtain first: Allocation/assessment guidance, masking and original collection materials
- Further research: Proposal: Record separate materials for design and outcome measurement. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Allocation generation/concealment, open-label status, and 180-day assessment/masking must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Allocation generation/concealment, open-label status, and 180-day assessment/masking to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M08 §8.1–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application
- Related sources: S01

### N05 · How do the 850 randomized participants differ from the 806 in the primary analysis?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: The preserved statement says TRAIN included only the 806 participants with observed primary outcomes among 850 randomized. The unfavorable-outcome denominators are 246/393 versus 300/413; no new exclusion counts or rates are calculated.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Reasons for unobserved/excluded outcomes, group follow-up/missingness and original ITT/sensitivity plans remain unverified. Existing content review remains incomplete.
- Reason for missing information: Reasons for unobserved/excluded outcomes, group follow-up/missingness and original ITT/sensitivity plans remain unverified.
- Required materials and conditions: Observed-outcome/completer analysis, group denominators 393/413, and missingness/exclusions
- Materials to obtain first: Participant flow, missingness/analysis populations and sensitivity analyses/SAP
- Further research: Proposal: Link randomized and observed populations and missingness. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Observed-outcome/completer analysis, group denominators 393/413, and missingness/exclusions must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Observed-outcome/completer analysis, group denominators 393/413, and missingness/exclusions to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M08 Table 8.2.a, M15 §15.3 and M19 §19.1.2–19.2.4; Design-specific adaptation is Chamgap design; M08 §8.2.2 and M15 §15.3.1; Chamgap application
- Related sources: S01

### N06 · How was unfavorable GOS-E 1~5 outcome at 180 days defined?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN's endpoint was unfavorable GOS-E 1~5 outcome at 180 days. Descriptions of scale levels, components/death, other functional scales or continuous scores are not added where absent from the summary.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Adjudication/questions, assessment window, scale/component results and original collection details remain unverified. Existing content review remains incomplete.
- Reason for missing information: Adjudication/questions, assessment window, scale/component results and original collection details remain unverified.
- Required materials and conditions: The scale, 1~5 cutoff, timing/adjudication and original component scope
- Materials to obtain first: GOS-E assessment/endpoint definitions, original outcome tables and prespecified plans
- Further research: Proposal: Link the unfavorable-outcome definition and individual functional materials. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering The scale, 1~5 cutoff, timing/adjudication and original component scope must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes The scale, 1~5 cutoff, timing/adjudication and original component scope to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation to each question is internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M08 Table 8.2.a, M04 §4.6.3; internal application
- Related sources: S01

### N07 · Which groups and analysis population underlie TRAIN's unfavorable-outcome counts and rates?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN's original unfavorable outcomes are preserved as 246/393 (62.6%) with the liberal strategy versus 300/413 (72.6%) with the restrictive strategy. They are not converted into rates among all 850 participants, injury-specific response rates or favorable-outcome rates.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Original group/denominator flow, subgroup events, missingness/censoring and exact assessment timing remain unverified. Existing content review remains incomplete.
- Reason for missing information: Original group/denominator flow, subgroup events, missingness/censoring and exact assessment timing remain unverified.
- Required materials and conditions: Original group labels and denominators for 246/393 (62.6%) and 300/413 (72.6%)
- Materials to obtain first: Original outcome/group-denominator tables and subgroup/follow-up tables
- Further research: Proposal: Document event/person and overall/subgroup denominators. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Original group labels and denominators for 246/393 (62.6%) and 300/413 (72.6%) must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Original group labels and denominators for 246/393 (62.6%) and 300/413 (72.6%) to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design
- Related sources: S01

### N08 · What are the interval, direction and analysis specifications for adjusted RR .86?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN's adjusted RR .86 (95% CI .79~.94), P=.002 is recorded in the original unfavorable-outcome comparison direction. It is not changed into a favorable-outcome RR, individual prediction or effect of transfusion exposure alone; no reciprocal or new effect is calculated.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Covariates, model/assumptions, missing-data handling and exact contrast/population remain unverified. Existing content review remains incomplete.
- Reason for missing information: Covariates, model/assumptions, missing-data handling and exact contrast/population remain unverified.
- Required materials and conditions: Unfavorable-outcome RR/CI/P, adjustment and distinction from absolute effects
- Materials to obtain first: Adjusted model/SAP and original result/interval tables
- Further research: Proposal: Link comparison direction and adjusted estimates. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Unfavorable-outcome RR/CI/P, adjustment and distinction from absolute effects must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Unfavorable-outcome RR/CI/P, adjustment and distinction from absolute effects to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application
- Related sources: S01

### N09 · How do TRAIN's absolute difference of −10%p and RR differ?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN's original absolute difference −10.0%p (95% CI −16.5~−3.6) and adjusted RR .86 are different estimates. No new difference is calculated from 62.6/72.6, and the sign is not changed to match HEMOTION's positive-difference coding.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. The exact absolute-difference contrast/adjustment, denominators, covariates and original tables remain unverified. Existing content review remains incomplete.
- Reason for missing information: The exact absolute-difference contrast/adjustment, denominators, covariates and original tables remain unverified.
- Required materials and conditions: Original absolute difference −10.0 (−16.5~−3.6), RR, scales and directions
- Materials to obtain first: Original absolute/relative-effect tables and contrast/model definitions
- Further research: Proposal: Record the sign and interval specifications for each estimate. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Original absolute difference −10.0 (−16.5~−3.6), RR, scales and directions must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Original absolute difference −10.0 (−16.5~−3.6), RR, scales and directions to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are Chamgap's own design; M08 §8.2.2, M15 §15.3.1; Chamgap's own application; M15 §15.3.1–15.3.3; Chamgap's own application
- Related sources: S01

### N10 · What is known about primary timing/outcome, prespecified analysis and multiplicity?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN's original primary endpoint was unfavorable GOS-E outcome at 180 days, analyzed in 806 with observed outcomes. Injury-specific, safety and other-timepoint results are not promoted to new primary endpoints or independent confirmation.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Protocol/SAP, prespecified multiplicity/subgroup/missingness plans and amendment history remain unverified. Existing content review remains incomplete.
- Reason for missing information: Protocol/SAP, prespecified multiplicity/subgroup/missingness plans and amendment history remain unverified.
- Required materials and conditions: The 180-day primary outcome, prespecified plan, and subgroup/safety hierarchy
- Materials to obtain first: Registration/protocol/SAP and endpoint hierarchy
- Further research: Proposal: Link plans for primary, secondary and subgroup analyses. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering The 180-day primary outcome, prespecified plan, and subgroup/safety hierarchy must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes The 180-day primary outcome, prespecified plan, and subgroup/safety hierarchy to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M08 Table 8.2.a, M04 §4.6.3; Chamgap's own application
- Related sources: S01

### N11 · What exposure information is represented by median transfusion volume of 2 versus 0 units?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN's original median transfusion volume of 2 versus 0 units is preserved. The median is not repurposed as every individual's exposure, total transfusion volume or a dose-response effect.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Timing, analysis population, distribution/blood types, crossover/additional transfusion and concomitant treatment remain unverified. Existing content review remains incomplete.
- Reason for missing information: Timing, analysis population, distribution/blood types, crossover/additional transfusion and concomitant treatment remain unverified.
- Required materials and conditions: Separate actual transfusion volume, assigned strategy, distribution/denominator/time
- Materials to obtain first: Actual exposure/distribution, adherence/crossover and concomitant treatment records
- Further research: Proposal: Link assigned strategies and actual blood exposure. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Separate actual transfusion volume, assigned strategy, distribution/denominator/time must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Separate actual transfusion volume, assigned strategy, distribution/denominator/time to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; own application; M03 §3.2.2–3.2.3; reverse-direction labels and test adaptations are our own design
- Related sources: S01

### N12 · Did HEMOTION test the same question as TRAIN's overall population?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: HEMOTION included traumatic brain injury only and compared 10 versus 7 g/dL; TRAIN included TBI/SAH/ICH and compared 9 versus 7. The populations and liberal thresholds are not treated as identical, and HEMOTION is not transferred as direct replication in SAH/ICH.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Exact eligibility/severity, baseline characteristics, treatment/exposure and comparability by injury remain unverified. Existing content review remains incomplete.
- Reason for missing information: Exact eligibility/severity, baseline characteristics, treatment/exposure and comparability by injury remain unverified.
- Required materials and conditions: Traumatic injury only and thresholds of 10 versus 7, versus mixed injuries and 9 versus 7
- Materials to obtain first: Both trials' characteristics/baseline and strategy/exposure tables
- Further research: Proposal: Record population/threshold differences and their relationship to results. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Traumatic injury only and thresholds of 10 versus 7, versus mixed injuries and 9 versus 7 must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Traumatic injury only and thresholds of 10 versus 7, versus mixed injuries and 9 versus 7 to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.1; detailed population conditions are our own design; M03 §3.2.2–3.2.3; reverse-direction labels and test adaptations are our own design; M04 §4.6.1–4.6.2, M15 §15.3.1; own application
- Related sources: S01, S02

### N13 · What do HEMOTION's 742 randomized and 722 analyzed participants represent?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: HEMOTION's 742 randomized and 722 analyzed participants are preserved. Its 68.4% versus 73.5% rates are not transferred to all 742 participants or TRAIN's 393/413 denominators; no new exclusion counts or rates are calculated.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Group analysis denominators, follow-up/missingness/exclusions and sensitivity/ITT plans remain unverified. Existing content review remains incomplete.
- Reason for missing information: Group analysis denominators, follow-up/missingness/exclusions and sensitivity/ITT plans remain unverified.
- Required materials and conditions: Randomized/analysis denominators, group-level missingness and actual outcomes
- Materials to obtain first: HEMOTION flow, original group outcomes/denominators and SAP
- Further research: Proposal: Link randomized/analysis populations and outcome denominators. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Randomized/analysis denominators, group-level missingness and actual outcomes must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Randomized/analysis denominators, group-level missingness and actual outcomes to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M08 Table 8.2.a, M15 §15.3 and M19 §19.1.2–19.2.4; Design-specific adaptation is Chamgap design; M08 §8.2.2 and M15 §15.3.1; Chamgap application
- Related sources: S02

### N14 · What do HEMOTION's unfavorable outcomes, adjusted difference and CI estimate?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: HEMOTION's original 68.4% versus 73.5%, adjusted absolute difference 5.4%p (95% CI −2.9~13.7) and null-result wording are preserved. No new difference, CI or RR is calculated from the rates, and nonsignificance is not changed into equivalence, zero effect or exclusion of important effects.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Exact group/coding of the adjusted difference, model, original P value, denominators and important-difference threshold remain unverified. Existing content review remains incomplete.
- Reason for missing information: Exact group/coding of the adjusted difference, model, original P value, denominators and important-difference threshold remain unverified.
- Required materials and conditions: 68.4/73.5%, adjusted 5.4%p (−2.9~13.7), and the original null-result wording
- Materials to obtain first: HEMOTION original tables, contrast/model and prespecified importance threshold
- Further research: Proposal: Document original intervals and estimation specifications. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering 68.4/73.5%, adjusted 5.4%p (−2.9~13.7), and the original null-result wording must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes 68.4/73.5%, adjusted 5.4%p (−2.9~13.7), and the original null-result wording to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are Chamgap's own design; M08 §8.2.2, M15 §15.3.1; Chamgap's own application; M15 §15.3.1–15.3.3; Chamgap's own application
- Related sources: S02

### N15 · Are assessment and GOS-E definitions identical at 180 days and six months?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN is preserved as 180-day GOS-E 1~5 and HEMOTION as six-month unfavorable GOS-E outcome. HEMOTION's exact cutoff/adjudication rules and assessment window are not filled with TRAIN's definition.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Both assessment windows/collection, HEMOTION's unfavorable-outcome definition and baseline-specific classification/weighting remain unverified. Existing content review remains incomplete.
- Reason for missing information: Both assessment windows/collection, HEMOTION's unfavorable-outcome definition and baseline-specific classification/weighting remain unverified.
- Required materials and conditions: TRAIN's 180-day 1~5 definition and HEMOTION's actual six-month definition/assessment window
- Materials to obtain first: Both trials' endpoint/assessment guidance and prespecified plans
- Further research: Proposal: Compare timing and scale specifications. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering TRAIN's 180-day 1~5 definition and HEMOTION's actual six-month definition/assessment window must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes TRAIN's 180-day 1~5 definition and HEMOTION's actual six-month definition/assessment window to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design; M08 Table 8.2.a, M03 §3.2.4; own application; M04 §4.6.1–4.6.2, M15 §15.3.1; own application
- Related sources: S01, S02

### N16 · How does the original positive/null conflict wording relate to the numbers?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: The original account describes TRAIN as positive and HEMOTION as null/opposing, and the subclaim C note describes conflict. Original rates, estimates and CIs are recorded together; the wording alone does not newly establish opposite effect signs or a proven difference under identical conditions.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. The cause of conflict, direct between-trial interaction, comparability and important-effect threshold remain unverified. Existing content review remains incomplete.
- Reason for missing information: The cause of conflict, direct between-trial interaction, comparability and important-effect threshold remain unverified.
- Required materials and conditions: Preserve original verdict/conflict wording alongside each rate, effect and interval
- Materials to obtain first: Both trials' original results/characteristics and prespecified comparison/interaction materials
- Further research: Proposal: Link original conclusion wording and quantitative results separately. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Preserve original verdict/conflict wording alongside each rate, effect and interval must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Preserve original verdict/conflict wording alongside each rate, effect and interval to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are our own design; M15 §15.3.1–15.3.3; own application; M04 §4.6.1–4.6.2, M15 §15.3.1; own application
- Related sources: S01, S02

### N17 · How are the original Korean/English descriptions of trial size and conclusions preserved?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: The Korean core summary's original 'larger contemporaneous HEMOTION' wording and the English description of a contemporaneous large trial remain in the full preserved source. Original 850/806 and 742/722 counts are used separately; that wording is not adopted as a new trial-size comparison/verdict fact, and the original is not corrected.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. New original-text review or correction of the wording/numeric context was not performed here. Existing content review remains incomplete.
- Reason for missing information: New original-text review or correction of the wording/numeric context was not performed here.
- Required materials and conditions: History of the original 'larger contemporaneous' wording, actual 850/742 counts and English account
- Materials to obtain first: Original correction materials or user feedback
- Further research: Proposal: Record version-specific sources for original wording and numbers. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering History of the original 'larger contemporaneous' wording, actual 850/742 counts and English account must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes History of the original 'larger contemporaneous' wording, actual 850/742 counts and English account to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.5, §4.6.3; current material-conversion limits reflect review scope and our own design; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are our own design
- Related sources: S01, S02

### N18 · Do population/threshold differences explain the cause of the conflict?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: The original counterview says populations and liberal thresholds differ, but these differences alone cannot explain the opposing conclusions and the cause is unknown. Differences are not newly confirmed as proven effect modification or causes.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Prespecified interactions, standardized comparisons, covariates/exposure and causal analyses remain unverified. Existing content review remains incomplete.
- Reason for missing information: Prespecified interactions, standardized comparisons, covariates/exposure and causal analyses remain unverified.
- Required materials and conditions: Differences in 9/10 versus 7 thresholds and mixed/traumatic populations, with cause unverified
- Materials to obtain first: Trial characteristics, prespecified interactions and comparative analysis materials
- Further research: Proposal: Record the unverified relationship between condition differences and causes of conflict. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Differences in 9/10 versus 7 thresholds and mixed/traumatic populations, with cause unverified must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Differences in 9/10 versus 7 thresholds and mixed/traumatic populations, with cause unverified to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.6.1–4.6.2, M15 §15.3.1; own application
- Related sources: S01, S02

### N19 · Can the overall acute-brain-injury effect be transferred separately to TBI, SAH and ICH?

Verification status: Unverified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN's overall result does not certify equal effect size separately in TBI/SAH/ICH. HEMOTION's traumatic-injury result is not transferred to hemorrhage subgroups, and subgroups are not counted as new independent trials.
- Why unverified: Required information is unverified in the preserved summary. Injury-specific denominators/events, effects/CIs, prespecified subgroups and interactions remain unverified. Existing content review remains incomplete.
- Reason for missing information: Injury-specific denominators/events, effects/CIs, prespecified subgroups and interactions remain unverified.
- Required materials and conditions: Mixed-population overall results, subgroup events/denominators and interaction
- Materials to obtain first: Injury-specific results, prespecified plans and interaction materials
- Further research: Proposal: Record overall/subgroup estimates and conditions separately. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Mixed-population overall results, subgroup events/denominators and interaction must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Mixed-population overall results, subgroup events/denominators and interaction to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.6.1–4.6.2, M15 §15.3.1; own application; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are our own design; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design
- Related sources: S01, S02

### N20 · Are trials, questions, timepoints and denominators kept separate when counting?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN and HEMOTION have separate original reports/conditions and their own randomized, analysis and safety denominators and 180-day/six-month outcomes. The parent/current sheet, questions and timepoints are not added as new independent trials or total participants.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Unique trial, participant and independent-replication totals have not been confirmed and remain unrecorded. Existing content review remains incomplete.
- Reason for missing information: Unique clinical trial, participant and independent replication totals have not been verified and are not recorded.
- Required materials and conditions: Report/trial/population links, shared denominators/endpoints and unverified unique totals
- Materials to obtain first: Report/trial/population/endpoint linkage materials, if supplied
- Further research: Proposal: Record study families and shared/duplicate relationships. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Report/trial/population links, shared denominators/endpoints and unverified unique totals must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Report/trial/population links, shared denominators/endpoints and unverified unique totals to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: Study/report distinction in M04 §4.6.1–4.6.2; Cohort/outcome linkage is Chamgap application; M04 §4.6.1–4.6.2 and M15 §15.3.1; Chamgap application
- Related sources: S01, S02

### N21 · What are TRAIN's funding, sponsorship and administrative roles?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN's original ESICM NeXT grant, La Fondation des Gueules Cassées, and University Hospital Brussels sponsorship/administrative support are preserved. Public/nonprofit support is not changed into absence of all product/company/staff-author/COI involvement or certification of independence.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Support agreements, product/blood support, authors/contributions, study/analysis/manuscript decision rights and COI remain unverified. Existing content review remains incomplete.
- Reason for missing information: Support agreements, product/blood support, authors/contributions, study/analysis/manuscript decision rights and COI remain unverified.
- Required materials and conditions: ESICM NeXT, Fondation and Brussels, distinguished from products/staff/COI
- Materials to obtain first: Original support/sponsorship roles, contributions/products and author/COI materials
- Further research: Proposal: Document funding and actual roles. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering ESICM NeXT, Fondation and Brussels, distinguished from products/staff/COI must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes ESICM NeXT, Fondation and Brussels, distinguished from products/staff/COI to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: Chamgap's own conditions for independence and attribution. The official methodological sections used in this example do not validate every detail of these items.
- Related sources: S01

### N22 · What funding scope is covered by HEMOTION's CIHR 'and others' wording?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: The original HEMOTION record names support from the Canadian Institutes of Health Research and others. Unlisted total funding, in-kind support or company roles are not newly filled in or inherited as verified independence.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Specific other funding, product support, staff/contributions/author COI and analysis/manuscript roles remain unverified. Existing content review remains incomplete.
- Reason for missing information: Specific other funding, product support, staff/contributions/author COI and analysis/manuscript roles remain unverified.
- Required materials and conditions: Listed funding and 'and others', with products/staff and actual roles unverified
- Materials to obtain first: Original total-support/in-kind and author/contribution/COI materials
- Further research: Proposal: Link funding wording and actual support/roles. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Listed funding and 'and others', with products/staff and actual roles unverified must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Listed funding and 'and others', with products/staff and actual roles unverified to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: Chamgap's own conditions for independence and attribution. The official methodological sections used in this example do not validate every detail of these items.
- Related sources: S02

### N23 · Were registration identifiers and actual prespecified plans read?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Both original registration identifiers are preserved. Identifiers and historical prespecification accounts are not inherited as registration/plan reading here or as fulfilled endpoint/missingness/subgroup conditions.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Original registration/amendment history, protocol/SAP and multiplicity/subgroup/missingness plans remain unread. Existing content review remains incomplete.
- Reason for missing information: Original registration/amendment history, protocol/SAP and multiplicity/subgroup/missingness plans remain unread.
- Required materials and conditions: NCT02968654/03260478 identifiers, protocol/SAP and amendments
- Materials to obtain first: Registration/plan copies or user-supplied materials
- Further research: Proposal: Link registration versions by report and endpoint. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering NCT02968654/03260478 identifiers, protocol/SAP and amendments must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes NCT02968654/03260478 identifiers, protocol/SAP and amendments to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.5–4.6 material collection/selection principles; acquisition/reading separation and hyperlink specifications are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application
- Related sources: S01, S02

### N24 · How do TRAIN's cerebral-ischemia safety denominators differ from the primary outcome?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Original cerebral ischemia of 35/397 (8.8%) versus 57/423 (13.5%), RR .65 (95% CI .44~.97), belongs to prespecified serious-adverse-event context. It is not transferred to the 246/393 and 300/413 primary-outcome denominators or overall neurologic improvement.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Safety denominators/collection, cerebral-ischemia definition/adjudication, timing and multiplicity/CI details remain unverified. Existing content review remains incomplete.
- Reason for missing information: Safety denominators/collection, cerebral-ischemia definition/adjudication, timing and multiplicity/CI details remain unverified.
- Required materials and conditions: Prespecified serious events, 35/397 and 57/423, and separate RR .65/CI specifications
- Materials to obtain first: Safety tables, prespecified plans and event collection/denominators
- Further research: Proposal: Record primary endpoints and cerebral-ischemia events/denominators separately. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Prespecified serious events, 35/397 and 57/423, and separate RR .65/CI specifications must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Prespecified serious events, 35/397 and 57/423, and separate RR .65/CI specifications to link the materials needed for the selected question with those currently available.
- Application exceptions: Address gaps in harm materials for the selected kidney-replacement independence/neurologic outcome. Survival dependence and original mortality/neurologic/safety wording are not used to judge overall safety or create harm rates, treatment-initiation/transfusion/threshold/suitability guidance.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M19 §19.1.2–19.2.4; own application; M19 §19.1.2–19.2.4; detailed distinctions are our own design; M19 §19.1.2–19.2.4; own application; M08 Table 8.2.a, M04 §4.6.3; own application
- Related sources: S01

### N25 · Do increased transfusion exposure and cerebral-ischemia findings establish overall safety?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: TRAIN's original median transfusion volume of 2 versus 0 units and cerebral-ischemia results are preserved separately. The no-increase wording for one cerebral-ischemia outcome is not changed into zero transfusion harm, long-term safety or certified individual suitability.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Other safety-event definitions/collection, groups/exposure/denominators, rare/long-term harms and COI details remain unverified. Existing content review remains incomplete.
- Reason for missing information: Other safety-event definitions/collection, groups/exposure/denominators, rare/long-term harms and COI details remain unverified.
- Required materials and conditions: Blood exposure, individual serious events and rare/long-term harms
- Materials to obtain first: Complete safety tables, actual exposure/follow-up and collection materials
- Further research: Proposal: Link blood exposure and endpoint-specific harms. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Blood exposure, individual serious events and rare/long-term harms must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Blood exposure, individual serious events and rare/long-term harms to link the materials needed for the selected question with those currently available.
- Application exceptions: Address gaps in harm materials for the selected kidney-replacement independence/neurologic outcome. Survival dependence and original mortality/neurologic/safety wording are not used to judge overall safety or create harm rates, treatment-initiation/transfusion/threshold/suitability guidance.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M19 §19.1.2–19.2.4; own application; M19 §19.1.2–19.2.4; detailed distinctions are our own design; M19 §19.2 design-specific harm questions; timing details are our own design; M19 §19.1.2–19.2.4; own application; Chamgap's own interpretation boundary. M19 principles are referenced; no official causality tool was run
- Related sources: S01

### N26 · Can 180-day unfavorable outcomes be extended to lifelong function or other patients/thresholds?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: The original materials cover each trial's 180-day/six-month outcomes. They do not create recommendations on lifelong function/mortality, other brain injuries/anemia/exposures, individual thresholds or transfusion selection/administration.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Long-term follow-up, individual prediction/vulnerable groups and direct evidence for other thresholds/populations remain unverified. Existing content review remains incomplete.
- Reason for missing information: Long-term follow-up, individual prediction/vulnerable groups and direct evidence for other thresholds/populations remain unverified.
- Required materials and conditions: Actual 180-day/six-month assessments, eligibility/exposure and out-of-scope conditions
- Materials to obtain first: Direct long-term or separate-condition materials, if supplied
- Further research: Proposal: Record evidence gaps by duration, population and exposure. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Actual 180-day/six-month assessments, eligibility/exposure and out-of-scope conditions must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Actual 180-day/six-month assessments, eligibility/exposure and out-of-scope conditions to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.2.1; detailed population conditions are our own design; M03 §3.2.2–3.2.3; reverse-direction labels and test adaptations are our own design; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are our own design
- Related sources: S01, S02

### N27 · What was actually read in the preserved summaries, URLs and external materials?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Both original bibliographic records/URLs and registration identifiers are retained, and the full preserved summary was read for production and marked as summary reading. External papers/plans and COI remain unread; historical review accounts or identifiers do not upgrade reading status.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. External access, abstract/full-text/registration reading and link/click tests were not performed. Existing content review remains incomplete.
- Reason for missing information: External access, abstract/full-text/registration reading and link/click tests were not performed.
- Required materials and conditions: Preserved summaries, TRAIN/HEMOTION URLs/registration and unread external materials
- Materials to obtain first: User-supplied materials and actual reading records
- Further research: Proposal: Record acquisition, reading and versions by material. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Preserved summaries, TRAIN/HEMOTION URLs/registration and unread external materials must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Preserved summaries, TRAIN/HEMOTION URLs/registration and unread external materials to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.5–4.6 material collection/selection principles; acquisition/reading separation and hyperlink specifications are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design
- Related sources: S01, S02

### N28 · How are original Korean/English text, verdicts/axes, dates and absent values preserved?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: The full source's Korean/English text, parent C56/Caution, unrecorded precision/false flags, empty corrections/deliberation, 2026-08-26 and original conflict/cross-check wording are preserved. Subclaim C/note and absent score/status/axes are not filled with parent values.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. The earlier production record performed no verdict-text translation, clinical full-text review, reassessment, correction or external update. Existing content review remains incomplete.
- Reason for missing information: The earlier production record performed no verdict-text translation, clinical full-text review, reassessment, correction or external update.
- Required materials and conditions: Subclaim C, parent C56, 2026-08-26, null/false and correction history
- Materials to obtain first: Original correction materials or user feedback
- Further research: Proposal: Link original versions/dates and the selected question. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Subclaim C, parent C56, 2026-08-26, null/false and correction history must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Subclaim C, parent C56, 2026-08-26, null/false and correction history to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design
- Related sources: S01, S02

### N29 · How are condition preservation, application and sheet production distinguished from content review?

Verification status: Partly verified  
Reading scope: Summary read; external material unread

- Current findings: Condition preservation, freezing, application, case production and content review are separate records. Existing content review remains incomplete; counts of rows, reports and materials are not unique clinical-trial or participant totals.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials are unread and existing content review remains incomplete. Existing content review remains incomplete, and original clinical materials have not been newly verified. Existing content review remains incomplete.
- Reason for missing information: Review of the existing content is incomplete and clinical source material was not newly verified.
- Required materials and conditions: Separate condition preservation/freezing/application, case production and incomplete content review
- Materials to obtain first: User review feedback and additional preserved materials
- Further research: Proposal: Record condition/production versions and user correction history. No new research, calculation or trial was performed.
- Conditions for verification: Original materials and analysis scope covering Separate condition preservation/freezing/application, case production and incomplete content review must be available, with unverified matters distinguished. Preserved statements are linked here; existing content review remains incomplete.
- Why this condition is needed: This item distinguishes Separate condition preservation/freezing/application, case production and incomplete content review to link the materials needed for the selected question with those currently available.
- Application exceptions: Limited to the stored summary for the selected formulation, population, endpoint and period. It does not substitute for numbers from other formulations/trials/endpoints or unread external material.
- Remaining uncertainty: This record links preserved-summary statements; it does not establish external-paper comparison, a new efficacy verdict or completed content review.
- Referenced methods: M04 §4.5–4.6 material collection/selection principles; acquisition/reading separation and hyperlink specifications are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design
- Related sources: S01, S02

## Evidence and sources

### S01

TRAIN

[PubMed](https://pubmed.ncbi.nlm.nih.gov/39382241/)

Materials actually read: Summary read; external material unread  
Findings recorded in the summary: 62.6% versus 72.6%, adjusted RR 0.86 (0.79~0.94), P=.002. Original absolute difference −10.0%p (CI −16.5~−3.6), adjusted RR and denominators 246/393 versus 300/413 are preserved separately. Safety cerebral-ischemia denominators, transfusion medians and overall/subgroup results are not merged, and no new favorable-outcome rates, differences/CIs or individual effects are calculated.  
Record level: Outcome wording in the stored summary  
Independent replication: S01 TRAIN/PMID39382241 is a 9-versus-7 g/dL strategy trial in a mixed TBI/SAH/ICH population across 72 ICUs in 22 countries, with 850 randomized and 806 analyzed with observed outcomes. Overall results, subgroups and safety denominators 397/423 are distinguished; equal effects across every brain-injury patient/subgroup are not established. The same report/groups/people, timepoints/endpoints and different questions/denominators are not added as new independent trials or participants. Report/material counts are not unique clinical totals; unique trial, participant and independent-replication totals remain unrecorded. S02 HEMOTION/PMID38869931 is a 10-versus-7 g/dL strategy trial in traumatic brain injury only, with 742 randomized and 722 analyzed. It differs from TRAIN's mixed-population 9-versus-7 strategy; the exact six-month GOS-E cutoff/adjudication specification is unverified in this summary. The same report/groups/people, timepoints/endpoints and different questions/denominators are not added as new independent trials or participants. Report/material counts are not unique clinical totals; unique trial, participant and independent-replication totals remain unrecorded.

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Stored summary | Stored file | Stored summary | Summary read | Only the stored JSON summary and bibliography were used for production. This does not constitute external verification or completed content review. |
| External paper | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Registration material | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Protocol | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Statistical analysis plan | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Funding, product-support and COI material | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |

### S02

HEMOTION

[PubMed](https://pubmed.ncbi.nlm.nih.gov/38869931/)

Materials actually read: Summary read; external material unread  
Findings recorded in the summary: 68.4% versus 73.5%, adjusted absolute difference 5.4%p (95% CI −2.9~13.7), null. Original rates and adjusted difference/interval are preserved separately. Signs are not changed to match TRAIN's absolute-difference coding, and no new RR, difference/CI, between-trial interaction or identical overall/subgroup effect is created.  
Record level: Outcome wording in the stored summary  
Independent replication: S01 TRAIN/PMID39382241 is a 9-versus-7 g/dL strategy trial in a mixed TBI/SAH/ICH population across 72 ICUs in 22 countries, with 850 randomized and 806 analyzed with observed outcomes. Overall results, subgroups and safety denominators 397/423 are distinguished; equal effects across every brain-injury patient/subgroup are not established. The same report/groups/people, timepoints/endpoints and different questions/denominators are not added as new independent trials or participants. Report/material counts are not unique clinical totals; unique trial, participant and independent-replication totals remain unrecorded. S02 HEMOTION/PMID38869931 is a 10-versus-7 g/dL strategy trial in traumatic brain injury only, with 742 randomized and 722 analyzed. It differs from TRAIN's mixed-population 9-versus-7 strategy; the exact six-month GOS-E cutoff/adjudication specification is unverified in this summary. The same report/groups/people, timepoints/endpoints and different questions/denominators are not added as new independent trials or participants. Report/material counts are not unique clinical totals; unique trial, participant and independent-replication totals remain unrecorded.

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Stored summary | Stored file | Stored summary | Summary read | Only the stored JSON summary and bibliography were used for production. This does not constitute external verification or completed content review. |
| External paper | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Registration material | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Protocol | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Statistical analysis plan | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |
| Funding, product-support and COI material | Public availability unverified; only bibliography links preserved | Unread; access not attempted | Not read | No external access or click testing was performed in the original preparation. URLs or registration identifiers alone do not upgrade acquisition/reading status. |

## Review criteria and methods

These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score.

- M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions and reasons for changes, and distinguish variations in interventions. · Preserved method HTML copies; no current method-content re-review or official tool execution
- M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish studies from reports and link them; do not omit a study solely because results are unreported. · Preserved method HTML copies; no current method-content re-review or official tool execution
- M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Define the outcome and effect of interest, then examine randomization, deviations, missing data, measurement and selective reporting. · Preserved method HTML copies; no current method-content re-review or official tool execution
- M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · Preserved method HTML copies; no current method-content re-review or official tool execution
- M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence rates. · Preserved method HTML copies; no current method-content re-review or official tool execution

## What the statuses mean

- Met: Status for necessary evidence confirmed after existing content review. No completion is declared in the current presentation.
- Partly verified: Some information in the stored summary is linked into the table. External comparison/content review is not complete.
- Unverified: The article leaves this unverified, or required material is absent from the current stored summary. This is distinct from zero, absence or safety.
- Review incomplete: Existing content review incomplete.
- Not reported: Not reported within the stored material actually read; not extended to the entire primary paper.
- Inaccessible: Means an actual access failure. Access not attempted here is not assigned this state.
- Not applicable: Not used as a substitute for an evidence gap.
- Conflicting data: Requires an observed disagreement under the same comparison criteria; not automatically judged in this production.
- Insufficient evidence for the conditions: Marks a gap in additional material required by the selected conditions; not a new efficacy grade.

## Change history

2026-10-10 · Public page/materials 1.0. Public pages and materials were created from the existing 29 items. No new clinical search, verification-status change or scoring was performed.