# Darbepoetin alfa × Neurodevelopment in preterm infants — Evidence sheet with separate follow-up unverified

Verdict 2925 · 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: Preterm infants with birth weight 500~1250 g, enrolled within 48 hours of birth; detailed baseline and eligibility information unread
- Ingredient, formulation and route: Historical research exposure to darbepoetin alfa; no recommendation on transfusion or developmental treatment selection
- Dose: The original 10µg/kg once weekly and 35-week stopping condition are retained as history only; no individual administration, dose or suitability guidance
- Comparator: Placebo/sham and a standardized transfusion protocol; details of the other arm in the three-arm trial and concurrent exposures unread
- Measured outcome: Original claim of improved neurodevelopment; subclaim '?', separate two-year secondary follow-up and direct instruments/values/denominators unverified
- Duration: The hospitalization/35-week research exposure and transfusion window are distinguished from separate two-year developmental follow-up; details of age definitions and actual duration unread
- Questions outside this scope: Combining mean transfusions, transfusion-free status, donors and developmental assessment as the same effect; Replacing '?' uniformly with D/B or inventing follow-up values, instruments or bibliography; Counting follow-up, two questions or the same infants as new independent evidence; Transferring effects from other ESAs or encephalopathy/cancer indications; Recommendations on transfusion, dose, administration, suitability, product selection or treatment

## Checklist items

### N01 · Were the selected claim and its subclaim grade distinguished from the parent verdict?

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

- Current findings: The selected claim is 'Improved neurodevelopment', with the subclaim grade retained as '?' from the stored summary. The note says this is a separate follow-up outcome rather than the primary endpoint of the main outcome paper. These are preserved separately from the parent B72 and Caution status.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Missing subclaim scores, status and axes are not filled with parent values. '?' is not uniformly replaced with D or confirmed B, and no new verdict is made.
- Reason for missing information: Missing subclaim scores, status and axes are not filled with parent values. '?' is not uniformly replaced with D or confirmed B, and no new verdict is made.
- Required materials and conditions: Separate preservation of the existing claim, grade, note and parent values
- Materials to obtain first: Missing subclaim scores, status and axes are not filled with parent values. '?' is not uniformly replaced with D or confirmed B, and no new verdict is made.
- Further research: Link additional material separately to each existing question and its parent context.
- Conditions for verification: Separate preservation of the existing claim, grade, note and parent values
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N02 · What were the actual birth weight, enrollment timing and preterm population?

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

- Current findings: The existing review summary states that preterm infants with birth weight 500~1250 g were included within 48 hours of birth.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not extend this to all newborns, other weights/gestational ages or other anemia/encephalopathy indications. Detailed gestational age, eligibility exclusions and baseline risk are unread.
- Reason for missing information: Do not extend this to all newborns, other weights/gestational ages or other anemia/encephalopathy indications. Detailed gestational age, eligibility exclusions and baseline risk are unread.
- Required materials and conditions: Original eligibility, baseline, birth weight, enrollment age and denominators
- Materials to obtain first: Do not extend this to all newborns, other weights/gestational ages or other anemia/encephalopathy indications. Detailed gestational age, eligibility exclusions and baseline risk are unread.
- Further research: Obtain the original eligibility, baseline, weight, gestational age and enrollment/treatment timing material.
- Conditions for verification: Original eligibility, baseline, birth weight, enrollment age and denominators
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N03 · Were darbepoetin and sham study identity distinguished from common care?

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

- Current findings: The existing review summary records darbepoetin, sham and standardized transfusion criteria.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not extend this to specific products, administration routes or other drugs, or fill in such details. Original details of concurrent exposures such as iron/nutrition are unread.
- Reason for missing information: Do not extend this to specific products, administration routes or other drugs, or fill in such details. Original details of concurrent exposures such as iron/nutrition are unread.
- Required materials and conditions: Original drug, placebo/sham, concurrent treatment, baseline care and actual exposure
- Materials to obtain first: Do not extend this to specific products, administration routes or other drugs, or fill in such details. Original details of concurrent exposures such as iron/nutrition are unread.
- Further research: Obtain the original drug, sham, common care, concurrent treatment and actual exposure material.
- Conditions for verification: Original drug, placebo/sham, concurrent treatment, baseline care and actual exposure
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N04 · Are 10µg/kg once weekly and the stopping time historical exposure conditions?

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

- Current findings: The existing Korean text retains 10µg/kg once weekly through 35 weeks of corrected gestational age, while the English text states through 35 weeks gestation as the research condition.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not turn this condition into individual instructions for administration, scheduling, stopping or suitability. Do not arbitrarily redefine the original gestational-age wording or certify that everyone actually completed treatment.
- Reason for missing information: Do not turn this condition into individual instructions for administration, scheduling, stopping or suitability. Do not arbitrarily redefine the original gestational-age wording or certify that everyone actually completed treatment.
- Required materials and conditions: Original study plan, dose, frequency, stopping time and actual exposure
- Materials to obtain first: Do not turn this condition into individual instructions for administration, scheduling, stopping or suitability. Do not arbitrarily redefine the original gestational-age wording or certify that everyone actually completed treatment.
- Further research: Obtain the original exposure plan, age definitions and tables of actual completion, missed doses, dose reduction or discontinuation.
- Conditions for verification: Original study plan, dose, frequency, stopping time and actual exposure
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N05 · Were 102 infants, 34 per arm and the three-arm design distinguished?

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

- Current findings: The existing review summary and evidence list describe a multicenter masked placebo-controlled three-arm trial with 102 infants and 34 per arm.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not invent the remaining arm's drug, dose or effect from the numbers in the two displayed arms. Outcome-specific analysis, dropout and follow-up denominators are separately unread.
- Reason for missing information: Do not invent the remaining arm's drug, dose or effect from the numbers in the two displayed arms. Outcome-specific analysis, dropout and follow-up denominators are separately unread.
- Required materials and conditions: Allocation, arm identity, arm-specific analyses, missing data and denominators
- Materials to obtain first: Do not invent the remaining arm's drug, dose or effect from the numbers in the two displayed arms. Outcome-specific analysis, dropout and follow-up denominators are separately unread.
- Further research: Obtain the original three-arm identities, allocation, analysis populations, missing data and participant flow.
- Conditions for verification: Allocation, arm identity, arm-specific analyses, missing data and denominators
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N06 · Were other study arms, other ESAs and verdict 2798 combined as the same result?

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

- Current findings: The existing review summary contains the three-arm trial and a cross-citation to high-dose epoetin alfa in verdict 2798 for a different encephalopathy indication.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not fill missing details of other arms with verdict 2798 values, or use that verdict to establish direct superiority/equivalence among ESAs or no effect on transfusion/development in preterm infants.
- Reason for missing information: Do not fill missing details of other arms with verdict 2798 values, or use that verdict to establish direct superiority/equivalence among ESAs or no effect on transfusion/development in preterm infants.
- Required materials and conditions: Original arm identities, ESAs, comparisons, indications and outcome relationships
- Materials to obtain first: Do not fill missing details of other arms with verdict 2798 values, or use that verdict to establish direct superiority/equivalence among ESAs or no effect on transfusion/development in preterm infants.
- Further research: Obtain original material separately for each drug, arm, indication and direct comparison.
- Conditions for verification: Original arm identities, ESAs, comparisons, indications and outcome relationships
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01, R02

### N07 · What were the roles of standardized restrictive transfusion criteria and clinicians' decisions?

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

- Current findings: The existing review summary records a standardized restrictive protocol based on Hb/Hct, respiratory support and symptoms, and actual blood administration records as the basis for treating transfusion as a hard endpoint.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not invent individual transfusion thresholds or procedures. Details of standardized implementation/deviations and other institutions' transfusion policies are unread.
- Reason for missing information: Do not invent individual transfusion thresholds or procedures. Details of standardized implementation/deviations and other institutions' transfusion policies are unread.
- Required materials and conditions: Transfusion thresholds, Hb/Hct, respiratory support, symptoms, records and deviations
- Materials to obtain first: Do not invent individual transfusion thresholds or procedures. Details of standardized implementation/deviations and other institutions' transfusion policies are unread.
- Further research: Obtain the original protocol, implementation/deviations, records, arm-specific criteria and denominators.
- Conditions for verification: Transfusion thresholds, Hb/Hct, respiratory support, symptoms, records and deviations
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N08 · Were mean transfusions per infant and the ± notation preserved as recorded?

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

- Current findings: Transfusions were 1.2±2.4 with darbepoetin versus 2.4±2.9 with placebo. The existing reader answer records a mean of 1.2 versus 2.4 transfusions per infant.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not newly identify ± as SD, SE or CI. Do not calculate event counts, transfused infant counts, total blood volume, donor counts, RR, P or CI.
- Reason for missing information: Do not newly identify ± as SD, SE or CI. Do not calculate event counts, transfused infant counts, total blood volume, donor counts, RR, P or CI.
- Required materials and conditions: Original counts, statistic, dispersion, arm order, duration and denominators
- Materials to obtain first: Do not newly identify ± as SD, SE or CI. Do not calculate event counts, transfused infant counts, total blood volume, donor counts, RR, P or CI.
- Further research: Obtain the original dispersion type, denominators, duration, count distribution, model and test.
- Conditions for verification: Original counts, statistic, dispersion, arm order, duration and denominators
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N09 · Was the original absolute reduction of 1.2 transfusions distinguished from preventing an infant from receiving a transfusion?

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

- Current findings: The existing reader answer describes an absolute reduction of 1.2 transfusions per infant.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not turn the mean difference into the same 1.2 reduction for every individual or a risk difference for receiving transfusion. There are no new mean differences, CIs, P values, total savings or event examples.
- Reason for missing information: Do not turn the mean difference into the same 1.2 reduction for every individual or a risk difference for receiving transfusion. There are no new mean differences, CIs, P values, total savings or event examples.
- Required materials and conditions: Original mean difference, effect, observation duration, denominators and uncertainty
- Materials to obtain first: Do not turn the mean difference into the same 1.2 reduction for every individual or a risk difference for receiving transfusion. There are no new mean differences, CIs, P values, total savings or event examples.
- Further research: Obtain the original mean difference, model, interval, test, duration and denominators.
- Conditions for verification: Original mean difference, effect, observation duration, denominators and uncertainty
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N10 · Were the hospitalization transfusion-free proportions of 59% and 38% distinguished from the original 21%p difference?

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

- Current findings: The original text records transfusion-free proportions of 59% versus 38%, an original absolute increase of 21%p.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not convert proportions into infant counts, RR, NNT or transfusion-free status for all periods. Details of original event counts, outcome denominators, CI and P are unread.
- Reason for missing information: Do not convert proportions into infant counts, RR, NNT or transfusion-free status for all periods. Details of original event counts, outcome denominators, CI and P are unread.
- Required materials and conditions: Transfusion-free definition, people, duration, denominators and original difference
- Materials to obtain first: Do not convert proportions into infant counts, RR, NNT or transfusion-free status for all periods. Details of original event counts, outcome denominators, CI and P are unread.
- Further research: Obtain the original transfusion-free criteria, arm denominators, infant counts, duration, CI and test.
- Conditions for verification: Transfusion-free definition, people, duration, denominators and original difference
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N11 · Are transfusion counts, transfusion-free status and donor exposure the same measure?

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

- Current findings: The existing summary and citations describe reduced transfusion counts and donor exposure, and record the transfusion-free proportion separately.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not fill missing donor values or totals with transfusion values. Do not count multiple measures or repeated transfusions as new participants or independent trials.
- Reason for missing information: Do not fill missing donor values or totals with transfusion values. Do not count multiple measures or repeated transfusions as new participants or independent trials.
- Required materials and conditions: Counts, people, donors, blood volume and each denominator
- Materials to obtain first: Do not fill missing donor values or totals with transfusion values. Do not count multiple measures or repeated transfusions as new participants or independent trials.
- Further research: Obtain the original definitions for each measure, people/events, denominators and donor/blood-volume material.
- Conditions for verification: Counts, people, donors, blood volume and each denominator
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N12 · Were the hospitalization/35-week stopping window and two-year developmental follow-up distinguished?

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

- Current findings: The parent record preserves the historical judgment that the period through 35 weeks matched the natural course of transfusion during hospitalization, and records separate two-year developmental follow-up.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not substitute long-term developmental assessment for the short intervention window or assume the same follow-up duration for all participants. Details of the exact end of transfusion observation, actual exposure and postnatal age are unread.
- Reason for missing information: Do not substitute long-term developmental assessment for the short intervention window or assume the same follow-up duration for all participants. Details of the exact end of transfusion observation, actual exposure and postnatal age are unread.
- Required materials and conditions: Intervention window, transfusion observation window, follow-up age, original duration and denominators
- Materials to obtain first: Do not substitute long-term developmental assessment for the short intervention window or assume the same follow-up duration for all participants. Details of the exact end of transfusion observation, actual exposure and postnatal age are unread.
- Further research: Obtain each original duration, age definition, exposure, discharge, follow-up and denominator.
- Conditions for verification: Intervention window, transfusion observation window, follow-up age, original duration and denominators
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N13 · What were the original computer block allocation, caregiver/investigator masking and sham procedures?

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

- Current findings: The existing review summary records computer block randomization, caregiver/investigator masking, sham and standardized transfusion criteria as the historical basis for counting no additional defects.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not certify independent review of the original paper's procedures in this work or newly certify absence of bias. Detailed allocation concealment, analyst, missing-data and assessor procedures are unread.
- Reason for missing information: Do not certify independent review of the original paper's procedures in this work or newly certify absence of bias. Detailed allocation concealment, analyst, missing-data and assessor procedures are unread.
- Required materials and conditions: Original allocation, concealment, masking, transfusion records and analysts
- Materials to obtain first: Do not certify independent review of the original paper's procedures in this work or newly certify absence of bias. Detailed allocation concealment, analyst, missing-data and assessor procedures are unread.
- Further research: Obtain the original allocation, masking, recording, analysis and missing-data procedures.
- Conditions for verification: Original allocation, concealment, masking, transfusion records and analysts
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N14 · What is the actual access status for primary transfusion, secondary developmental follow-up and registration plans?

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

- Current findings: The existing review summary states that transfusion count was prespecified primary, while neurodevelopment was a planned separate two-year secondary follow-up rather than primary in the main paper. The registration identifier is NCT00334737.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Registrations, full texts, plans and follow-up reports are not newly read. Do not invent test P values, α, ordering, multiplicity or changes to follow-up plans.
- Reason for missing information: Registrations, full texts, plans and follow-up reports are not newly read. Do not invent test P values, α, ordering, multiplicity or changes to follow-up plans.
- Required materials and conditions: Original endpoint hierarchy, registration, protocol, SAP, changes and multiplicity
- Materials to obtain first: Registrations, full texts, plans and follow-up reports are not newly read. Do not invent test P values, α, ordering, multiplicity or changes to follow-up plans.
- Further research: Obtain original registration, plans, hierarchy, changes, multiplicity and analysis-population material.
- Conditions for verification: Original endpoint hierarchy, registration, protocol, SAP, changes and multiplicity
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N15 · Were the main paper, separate follow-up and relationships among the same participants distinguished?

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

- Current findings: The existing citation is the Ohls 2013 main paper, and the existing review summary describes planned/published separate two-year follow-up. It does not provide the specific bibliography, URL or result tables of that follow-up paper.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not count follow-up assessments of the same trial, two questions or other ESAs as independent trials or new participants. Final independent counts and total participants remain null.
- Reason for missing information: Do not count follow-up assessments of the same trial, two questions or other ESAs as independent trials or new participants. Final independent counts and total participants remain null.
- Required materials and conditions: Original reports, follow-up bibliography, registration, assessment age and population mapping
- Materials to obtain first: Do not count follow-up assessments of the same trial, two questions or other ESAs as independent trials or new participants. Final independent counts and total participants remain null.
- Further research: Obtain the original follow-up bibliography, registration, arm-specific assessments and population/follow-up mapping.
- Conditions for verification: Original reports, follow-up bibliography, registration, assessment age and population mapping
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N16 · What are the gaps in direct neurodevelopmental effects, instruments and denominators?

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

- Current findings: The existing review summary describes separate two-year secondary follow-up but does not provide the developmental scores, between-arm effects, CIs, P values, original instruments or assessment denominators. The subclaim grade '?' remains unchanged.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not fill developmental effects with transfusion values or encephalopathy values for other ESAs. There are no new scale names, effects, scores, grades or clinical confirmations.
- Reason for missing information: Do not fill developmental effects with transfusion values or encephalopathy values for other ESAs. There are no new scale names, effects, scores, grades or clinical confirmations.
- Required materials and conditions: Original follow-up paper, assessment instruments, original scales, arm denominators, effects and intervals
- Materials to obtain first: Do not fill developmental effects with transfusion values or encephalopathy values for other ESAs. There are no new scale names, effects, scores, grades or clinical confirmations.
- Further research: Obtain the original follow-up paper, instruments, denominators, models, effects, intervals and tests.
- Conditions for verification: Original follow-up paper, assessment instruments, original scales, arm denominators, effects and intervals
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N17 · Were two-year assessment age, survivors, dropout, missing data and repeated assessments distinguished?

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

- Current findings: The stored summary records a two-year follow-up plan and separate outcomes.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not invent corrected-age definitions, survivor denominators, assessment completion, dropout, repeated assessments or institution-specific values. Do not use the initial 102 infants as the follow-up completer denominator.
- Reason for missing information: Do not invent corrected-age definitions, survivor denominators, assessment completion, dropout, repeated assessments or institution-specific values. Do not use the initial 102 infants as the follow-up completer denominator.
- Required materials and conditions: Corrected/chronological age, assessment population, survival, dropout, instruments and missing-data handling
- Materials to obtain first: Do not invent corrected-age definitions, survivor denominators, assessment completion, dropout, repeated assessments or institution-specific values. Do not use the initial 102 infants as the follow-up completer denominator.
- Further research: Obtain the original assessment age, survival/follow-up flow, arm denominators, instruments and missing-data handling.
- Conditions for verification: Corrected/chronological age, assessment population, survival, dropout, instruments and missing-data handling
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N18 · Were primary/secondary hierarchy, multiple developmental scales and clinical function established?

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

- Current findings: The existing review summary states that development was separate secondary follow-up rather than primary in the main paper.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not newly decide which developmental scales, subscales, clinical disabilities or functions were prespecified key outcomes. Do not transfer transfusion success to success across multiple developmental outcomes.
- Reason for missing information: Do not newly decide which developmental scales, subscales, clinical disabilities or functions were prespecified key outcomes. Do not transfer transfusion success to success across multiple developmental outcomes.
- Required materials and conditions: Original secondary-outcome plan, scales, multiplicity, models, function and plan changes
- Materials to obtain first: Do not newly decide which developmental scales, subscales, clinical disabilities or functions were prespecified key outcomes. Do not transfer transfusion success to success across multiple developmental outcomes.
- Further research: Obtain the original follow-up plan, scales, hierarchy, changes, multiplicity and clinical-function material.
- Conditions for verification: Original secondary-outcome plan, scales, multiplicity, models, function and plan changes
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N19 · Was a separate follow-up report certified as an independent trial or individual neuroprotection?

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

- Current findings: There is only a reference to separate follow-up of the same trial; the specified existing review summary contains no corresponding bibliography or effects.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. A reference to follow-up publication alone does not establish independent replication, neuroprotection, individual effects or confirmation for other ESAs/indications.
- Reason for missing information: A reference to follow-up publication alone does not establish independent replication, neuroprotection, individual effects or confirmation for other ESAs/indications.
- Required materials and conditions: Original trial, same population, follow-up bibliography, drugs and direct long-term outcomes
- Materials to obtain first: A reference to follow-up publication alone does not establish independent replication, neuroprotection, individual effects or confirmation for other ESAs/indications.
- Further research: Obtain the original registration, follow-up bibliography, same-population mapping and direct long-term outcomes.
- Conditions for verification: Original trial, same population, follow-up bibliography, drugs and direct long-term outcomes
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01, R02

### N20 · What are the small-study, original sample-size design and precision gaps?

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

- Current findings: The existing review summary records 102 infants, 34 per arm, a sample-size plan adding dropout allowance to 27 per arm, and the historical judgment of one small-study item.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not convert this into new power, success probabilities, parent scores or subclaim scores. Original assumption, MCID and CI details are unread, and there is no new sample-size calculation.
- Reason for missing information: Do not convert this into new power, success probabilities, parent scores or subclaim scores. Original assumption, MCID and CI details are unread, and there is no new sample-size calculation.
- Required materials and conditions: Original size, assumptions, plan, dropout, intervals and clinical importance
- Materials to obtain first: Do not convert this into new power, success probabilities, parent scores or subclaim scores. Original assumption, MCID and CI details are unread, and there is no new sample-size calculation.
- Further research: Obtain the original size assumptions, power, dropout handling, intervals and clinical boundaries.
- Conditions for verification: Original size, assumptions, plan, dropout, intervals and clinical importance
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N21 · Were public/nonprofit research funding and Amgen antibody assays distinguished?

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

- Current findings: Support from Thrasher Research Fund, Colorado CTSI and NIH/NCRR/NCATS and Amgen's antibody assay work are retained. The existing review summary records that study-drug supply and trial funding were not disclosed.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not turn antibody assays into external efficacy analysis of the entire trial or certification of no study-drug/funding provision. Employee authors and other roles are separately unread.
- Reason for missing information: Do not turn antibody assays into external efficacy analysis of the entire trial or certification of no study-drug/funding provision. Employee authors and other roles are separately unread.
- Required materials and conditions: Cash, products/in-kind support, assay provision, affiliations, analysis and roles
- Materials to obtain first: Do not turn antibody assays into external efficacy analysis of the entire trial or certification of no study-drug/funding provision. Employee authors and other roles are separately unread.
- Further research: Obtain original disclosures of cash, drugs/in-kind support, assays, affiliations, design, analysis and writing.
- Conditions for verification: Cash, products/in-kind support, assay provision, affiliations, analysis and roles
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N22 · Were similar prematurity morbidity/ROP and the original safety denominators distinguished?

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

- Current findings: The original safety text describes similar prematurity morbidity and retinopathy of prematurity across arms; the parent safety status is Caution.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not turn this into absence of all harms, equivalence or zero events for a specific harm. Details of each original event, denominator, CI, P, relatedness and collection are unread.
- Reason for missing information: Do not turn this into absence of all harms, equivalence or zero events for a specific harm. Details of each original event, denominator, CI, P, relatedness and collection are unread.
- Required materials and conditions: Harm definitions, grades, events/people, exposure, denominators and relatedness
- Materials to obtain first: Do not turn this into absence of all harms, equivalence or zero events for a specific harm. Details of each original event, denominator, CI, P, relatedness and collection are unread.
- Further research: Obtain original harm definitions, arm-specific events/people, denominators, exposure, relatedness and tests.
- Conditions for verification: Harm definitions, grades, events/people, exposure, denominators and relatedness
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N23 · Was a trial with 102 infants used to exclude rare/long-term harms or discontinuations?

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

- Current findings: The existing review summary records that 102 infants are too few to exclude rare harms, and that long-term neurodevelopment and safety are separate questions.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Retain the original blood pressure, thrombosis and blood-count monitoring text as history only; do not create implementation instructions, new risk rates, P values, CIs or long-term safety claims.
- Reason for missing information: Retain the original blood pressure, thrombosis and blood-count monitoring text as history only; do not create implementation instructions, new risk rates, P values, CIs or long-term safety claims.
- Required materials and conditions: Rare harms, actual exposure, duration, discontinuations and safety population
- Materials to obtain first: Retain the original blood pressure, thrombosis and blood-count monitoring text as history only; do not create implementation instructions, new risk rates, P values, CIs or long-term safety claims.
- Further research: Obtain the original safety population, actual exposure, discontinuations, collection and rare/long-term harm material.
- Conditions for verification: Rare harms, actual exposure, duration, discontinuations and safety population
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

### N24 · Were development and other ESAs/indications combined as the same harm or clinical effect?

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

- Current findings: The original verdict 2798 cross-citation concerns high-dose epoetin alfa for hypoxic-ischemic encephalopathy treatment: the same ESA class but a different indication.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Do not transfer cancer/encephalopathy judgments for other indications to transfusion or development in preterm infants. Do not create instructions on product/transfusion/drug/treatment selection, use or suitability.
- Reason for missing information: Do not transfer cancer/encephalopathy judgments for other indications to transfusion or development in preterm infants. Do not create instructions on product/transfusion/drug/treatment selection, use or suitability.
- Required materials and conditions: Developmental outcomes, other drugs, populations, indications and direct comparisons
- Materials to obtain first: Do not transfer cancer/encephalopathy judgments for other indications to transfusion or development in preterm infants. Do not create instructions on product/transfusion/drug/treatment selection, use or suitability.
- Further research: Obtain direct effects/harms and report relationships for each population, drug and indication.
- Conditions for verification: Developmental outcomes, other drugs, populations, indications and direct comparisons
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01, R02

### N25 · Were original bibliography, cross-citations, registration identifiers and access to follow-up material distinguished?

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

- Current findings: Ohls 2013 PubMed PMID23776118, NCT00334737 and the original link to related verdict 2798 are retained. The existing review summary contains no separate follow-up bibliography.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. External abstracts, full texts, registrations, plans, follow-up reports and linked verdicts are unread, with no separate link testing. Do not invent DOIs, URLs or paper titles.
- Reason for missing information: External abstracts, full texts, registrations, plans, follow-up reports and linked verdicts are unread, with no separate link testing. Do not invent DOIs, URLs or paper titles.
- Required materials and conditions: Reports/related verdicts, original URLs, registration and material-specific access status
- Materials to obtain first: External abstracts, full texts, registrations, plans, follow-up reports and linked verdicts are unread, with no separate link testing. Do not invent DOIs, URLs or paper titles.
- Further research: Link user-provided original material by report type, assessment age and access status.
- Conditions for verification: Reports/related verdicts, original URLs, registration and material-specific access status
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01, R02

### N26 · Were the Korean/English texts, axes, reference date, corrections, empty values, candidate history and production status retained?

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

- Current findings: The original 2026-08-26 date, empty correction/deliberation values, parent B72, Caution, axes, Korean/English texts, selected subclaim B/'?' and notes are preserved.
- Why unverified: Only the relevant information in the stored summary is recorded; detailed original material and user review remain outstanding. Original judgments of hard endpoints, independence and design defects are historical, not certification of review in this work. Missing subclaim values are not filled, and the original review-pending/production-eligibility labels are history.
- Reason for missing information: Original judgments of hard endpoints, independence and design defects are historical, not certification of review in this work. Missing subclaim values are not filled, and the original review-pending/production-eligibility labels are history.
- Required materials and conditions: Distinguishing the selected verdict record, complete parent, languages and history from current production
- Materials to obtain first: Original judgments of hard endpoints, independence and design defects are historical, not certification of review in this work. Missing subclaim values are not filled, and the original review-pending/production-eligibility labels are history.
- Further research: Link only user material/decisions as separate events after preserving the complete original text.
- Conditions for verification: Distinguishing the selected verdict record, complete parent, languages and history from current production
- Why this condition is needed: Case-specific production conditions recording the selected claim, endpoint, denominator, time, study identity and interpretation boundaries
- Application exceptions: Unread material, other questions, other products and out-of-scope results do not stand in for fulfillment, zero effect or safety.
- Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
- Referenced methods: Improved neurodevelopment
- Related sources: R01

## Evidence and sources

### R01

Ohls RK, Christensen RD, Kamath-Rayne BD, et al. A Randomized, Masked, Placebo-Controlled Study of Darbepoetin Alfa in Preterm Infants. Pediatrics. 2013;132(1):e119-e127. PMID: 23776118.

[PubMed](https://pubmed.ncbi.nlm.nih.gov/23776118/)

Materials actually read: Summary read; external or linked material unread  
Findings recorded in the summary: Darbepoetin 1.2±2.4 versus placebo 2.4±2.9 transfusions; transfusion-free 59% versus 38%  
Record level: Existing review summary; no comparison with the external original report  
Independent replication: The main transfusion paper of the same three-arm trial, a reference to separate two-year follow-up and two subclaim questions; follow-up bibliography/denominators not acquired. Verdict 2798 is a cross-citation to an existing verdict for another ESA and encephalopathy treatment; linked material unread and not independent replication of darbepoetin in preterm infants. Family IDs link relationships, not certified independent counts; events, composite components, institutions, cross-citations and the same participants are not newly counted as independent evidence.

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| local_summary | Original URL preserved | Summary read | Summary read | Preserved parent verdict summary; report-specific links to the same stored summary copy |
| abstract | Original URL preserved | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete |
| fulltext | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete |
| registration | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete |
| protocol_sap | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete |

### R02

High-dose epoetin alfa with no benefit × Neonatal hypoxic-ischemic encephalopathy: verdict 2798 has grade D and 34 points.

[Official source](https://chamgap.com/verdicts/cognition/high-dose-epoetin-hypothermia-neonatal-hie-death-neurodevelopmental-disability/)

Materials actually read: Summary read; external or linked material unread  
Findings recorded in the summary: The same ESA class, but a different indication: encephalopathy treatment.  
Record level: Only the original cross-citation summary is preserved; no newly read clinical evidence for the other ESA/indication  
Independent replication: The main transfusion paper of the same three-arm trial, a reference to separate two-year follow-up and two subclaim questions; follow-up bibliography/denominators not acquired. Verdict 2798 is a cross-citation to an existing verdict for another ESA and encephalopathy treatment; linked material unread and not independent replication of darbepoetin in preterm infants. Family IDs link relationships, not certified independent counts; events, composite components, institutions, cross-citations and the same participants are not newly counted as independent evidence.

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| local_summary | Original URL preserved | Summary read | Summary read | Preserved parent verdict summary; report-specific links to the same stored summary copy |
| source_link | Original URL preserved | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete |
| fulltext | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete |
| registration | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete |
| protocol_sap | No separate URL in the original material | Not read | Not read | External or linked verdict material unread; a URL does not mean reading or review is complete |

## 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. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing
- 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. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing
- 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. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing
- 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. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing
- 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. · Existing stored methodological links reused for preparation; no current review, reassessment of methodological content or external-link testing

## What the statuses mean

- Partly verified: Some information is in the stored summary; detailed original material remains unverified. This does not certify passed review or clinical efficacy
- Unverified: Detailed materials for the selected condition could not be established within the stored scope; this does not mean zero effect, zero studies or safety
- Review incomplete: Awaiting user review
- Met: Use only within the relevant condition's scope after user review; no automatic display in this preparation
- Not reported: Distinguish only within materials actually read; do not turn unread external materials into unreported findings
- Inaccessible: Not applied during this preparation because actual access was not tested
- Not applicable: Use with a reason for non-applicability based on an explicit question boundary
- Conflicting data: Judge after actual material comparison; review was not performed during this preparation
- Insufficient evidence for the conditions: Do not use as a clinical grade encompassing currently unread materials

## Change history

2026-10-10 · Public page/materials 1.0. The reader view and materials were prepared from the existing 26 items. No new clinical search, verification-status changes or scoring were performed.