{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3088-main", "verdict_number": "3088", "title": "Added riboflavin (vitamin B2) × Hemoglobin increase in anemic pregnant women receiving iron and folate", "view_version": "1.0", "view_created_date": "2026-11-01", "criteria_version": "NGM-v3088-B2-IFB-IF-ANEMIC-PREGNANCY-HB-1.0", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-15", "review_scope": { "materials_read": "Preserved Korean and English manuscripts and case-specific records of criteria and their application", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "No external clinical abstracts, full texts, registries, or analysis plans were newly read. Historical access records are distinguished from the preserved summaries read in this work. The original verdict, numerical values, and unverified information have been preserved; no new search, calculation, or reassessment was performed.", "date_meaning": "This is the date the preserved materials were reviewed, not the date of a new search of the clinical literature." }, "claim_context": { "population": "Pregnant women selected for anemia by Hb; not all confirmed to have iron-deficiency anemia", "intervention": "Supplementation with added riboflavin (vitamin B2)", "dose": "The principal analysis question concerns adding B2 1.0 mg/day; the 5 mg from another study is not pooled with it", "comparator": "The same iron 60 mg/day and folic acid 400 μg/day; excludes arms with added vitamin A", "endpoint": "Between-group difference in the change in blood Hb concentration; distinguished from anemia prevalence and combined-nutrient results", "duration": "The principal analysis question covers 2 months; longer-term and postpartum persistence remain unverified", "excluded_extensions": [ "Does this Hb question require a judgment on the optimal dose of 1 mg versus 5 mg?", "Does this question require a judgment on persistence beyond 2 months or on postpartum effects?", "Does the Hb question require evidence of benefit for maternal and fetal clinical events?" ] }, "requirements": [ { "item_id": "N01", "question_type": "One question about an added treatment", "question": "Is the single question in this table IFB versus IF, with only B2 added to the same iron and folate?", "needed": "Corrections to the definition of the current claim being judged, population, IFB/IF components, endpoint, and timeframe, or new original source material.", "role": "Required", "role_reason": "The criteria for a single question about an added treatment must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information about this single question on an added treatment with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "The question remains anchored at its original source location: a comparison adding only B2 to the same iron and folate treatment in pregnant women selected for anemia by Hb, with change in blood Hb as the outcome.", "basis": "Question-clarification principles in M03 §3.1 and §3.2.1–3.2.4; detailed rules for separating comparisons are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3 and M08 §8.2.2–8.2.3; internal application — an internal adaptation for a single question about an added treatment.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the components of each arm against the question-definition table and review the selection decisions that exclude vitamin A add-on arms and the anemia-prevalence question.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The original effect field (/ko/effect) and the definition of the question being judged fix the outcome as an increase in Hb in anemic pregnant women receiving iron and folate. The principal comparison is Ma’s IFB versus IF, distinguished from the IFAB combination arm and from anemia treatments as a whole.", "condition_status": "Met", "status_reason": "The definition of the single original principal comparison (main) and its exclusion boundaries were verified in the currently preserved manuscript. This is separate from verifying the magnitude of the Hb effect.", "missingness": "The principal IFB versus IF comparison and the scope of exclusions were verified. This does not mean that the magnitude of the Hb effect was verified, and external original source material was not directly read in this work.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Corrections to the definition of the current claim being judged, population, IFB/IF components, endpoint, and timeframe, or new original source material." }, { "item_id": "N02", "question_type": "Selection of anemic pregnant women", "question": "Have the Hb eligibility criteria, stage of pregnancy, and baseline characteristics of the anemic pregnant women been verified?", "needed": "Ma’s Hb eligibility threshold, gestational age, recruitment/exclusion criteria, and baseline-characteristics table by arm.", "role": "Required", "role_reason": "The criteria for selecting anemic pregnant women must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information on the selection of anemic pregnant women with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "The Hb eligibility threshold, stage of pregnancy, recruitment/exclusion criteria, and baseline Hb can be linked to the relevant IFB/IF population.", "basis": "M03 §3.2.1; detailed population criteria are internally designed — an internal adaptation for the selection of anemic pregnant women.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the original eligibility criteria with the flow diagram and baseline table to extract the Hb definition and stage of pregnancy, and review limitations on applicability to other maternal populations.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The population consists of pregnant women selected for anemia by Hb. The current manuscript does not provide the Hb threshold, gestational age, detailed inclusion/exclusion criteria, or the complete baseline characteristics by arm as verified information.", "condition_status": "Partly verified", "status_reason": "The population has been identified as pregnant women with anemia, but material is still needed to verify the detailed selection criteria and baseline distributions.", "missingness": "The population was verified as pregnant women with anemia, but the Hb eligibility threshold, gestational age, recruitment and exclusion criteria, and complete baseline characteristics by arm remain unverified.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Ma’s Hb eligibility threshold, gestational age, recruitment/exclusion criteria, and baseline-characteristics table by arm." }, { "item_id": "N03", "question_type": "Causes of anemia", "question": "Have the causes of anemia and the presence or absence of iron deficiency in IFB/IF participants been classified?", "needed": "Diagnostic methods for each cause of anemia, iron-status indicators, the composition of the IFB/IF arms by cause, and separate results by cause.", "role": "Required", "role_reason": "The criteria concerning the causes of anemia must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information on the causes of anemia with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "The methods for determining iron deficiency and other causes, and the composition of each arm, are linked to the relevant participants.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed — an internal adaptation for the causes of anemia.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Distinguish Hb-based selection from a diagnosis of iron deficiency, review the classification of causes, and check whether the results by cause come from planned comparisons.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "A complete classification of the causes of Hb-defined anemia remains unverified. Do not classify all participants as having iron-deficiency anemia or generalize the findings to treatment effects for all anemia.", "condition_status": "Unverified", "status_reason": "Hb-based selection alone does not verify diagnoses by cause or the presence or absence of iron deficiency.", "missingness": "Diagnoses by cause and the presence or absence of iron deficiency in Hb-defined anemia, the composition of each arm by cause, and separate results by cause remain unverified. Not all participants can be confirmed to have iron-deficiency anemia.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Diagnostic methods for each cause of anemia, iron-status indicators, the composition of the IFB/IF arms by cause, and separate results by cause." }, { "item_id": "N04", "question_type": "Baseline B2 status", "question": "Have baseline B2 status and the method for identifying deficiency in Ma’s participants been verified?", "needed": "Ma’s methods for measuring baseline vitamin status, deficiency thresholds, distributions by arm, and prespecified analysis plan.", "role": "Required", "role_reason": "The criteria concerning baseline B2 status must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information on baseline B2 status with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Verify participants’ baseline B2 indicators/thresholds and distributions, and the plan for analyzing effect modification.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed — an internal adaptation for baseline B2 status.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Extract the assessment of B2 status separately from Hb-based selection, and review whether there is a planned between-group comparison within the deficient stratum.", "current_reports": [ "S23", "S10" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The full details of baseline vitamin status and the method for identifying deficiency in the principal eligible population are blank/unverified. Do not transfer the eligibility criteria for RIBOFEM’s healthy women with low B2 status to Ma’s pregnant women.", "condition_status": "Unverified", "status_reason": "No material is available to verify the presence or absence of B2 deficiency or its distribution in this population of pregnant women.", "missingness": "Methods for measuring baseline B2, deficiency thresholds, distributions by arm, and the relevant prespecified analysis plan for Ma’s pregnant women remain unverified. Do not fill this gap with the eligibility criteria for RIBOFEM’s healthy women.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Ma’s methods for measuring baseline vitamin status, deficiency thresholds, distributions by arm, and prespecified analysis plan." }, { "item_id": "N05", "question_type": "Molecule and formulation", "question": "Have the molecule, product, and detailed formulation of the B2 preparation actually used been verified?", "needed": "Information on the composition/product, detailed formulation, release profile, and manufacture of Ma’s trial preparation.", "role": "Required", "role_reason": "The criteria concerning the molecule and formulation must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information on the molecule and formulation with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "The identity of riboflavin is linked to the product, formulation, release profile, and information on actual administration.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed — an internal adaptation for the molecule and formulation.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare trial-preparation records to extract the identity of riboflavin, the product, and the release profile, and exclude results for other B-vitamin types or formulations.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The molecule riboflavin is verified. The detailed formulation, release profile, and production origin, such as synthesis or fermentation, remain unverified in the decisive abstract. Plant-part classification does not apply to this question about a molecule.", "condition_status": "Partly verified", "status_reason": "The molecule has been verified, but the detailed formulation cannot be filled in as a verified value.", "missingness": "The molecule riboflavin was verified, but the detailed formulation, release profile, and production origin of the trial product remain unverified. The plant part used does not apply to this question about a molecule.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Information on the composition/product, detailed formulation, release profile, and manufacture of Ma’s trial preparation." }, { "item_id": "N06", "question_type": "Actual route of administration", "question": "Is the actual route of administration in Ma’s IFB/IF arms explicitly stated?", "needed": "Methods material explicitly stating Ma’s actual route of administration and formulation.", "role": "Required", "role_reason": "The criteria concerning the actual route of administration must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information on the actual route of administration with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Verify the route of administration in the decisive study’s actual Methods section. An oral-route label in the target question alone does not meet this criterion.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed — an internal adaptation for the actual route of administration.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the oral-route token (oral) in the question being judged with the actual route in the trial methods as separate records, and update the verification status of the observed route.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The verdict concerns a question about oral supplementation. Ma’s abstract does not specify the route of administration or detailed formulation, so the route value in the preserved study information (route.value) is blank/not_reported.", "condition_status": "Unverified", "status_reason": "The route specified in the question is fixed, but the actual route is not reported in the accessed decisive abstract, and the full text was not read in this work either.", "missingness": "The question concerns oral supplementation, but Ma’s abstract does not specify the actual route of administration or detailed formulation. The full-text methods material needed to verify these details was not read in this work.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Methods material explicitly stating Ma’s actual route of administration and formulation." }, { "item_id": "N07", "question_type": "Added B2 dose", "question": "Is the nominal added B2 dose in the principal comparison 1.0 mg/day?", "needed": "Corrections to Ma’s supplementation doses by arm, or records of actual administration.", "role": "Required", "role_reason": "The criteria concerning the added B2 dose must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information on the added B2 dose with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "The nominal B2 supplementation dose for IFB versus IF matches the original data structure. It is distinguished from actual intake and adherence.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3 and M08 §8.2.2–8.2.3; internal application — an internal adaptation for the added B2 dose.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Verify the prescribed dose in each arm, and do not add the 5 mg from another study or total dietary intake to this nominal added dose.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The dose value in the preserved study information (dose.value) and the supplementation-dose value (supplement_dose.value) are 1.0. The principal comparison adds B2 1.0 mg/day; Suprapto’s 5 mg is not pooled with it.", "condition_status": "Met", "status_reason": "The nominal added dose in the principal comparison was verified in the original data structure, without extending its meaning to the dose actually taken.", "missingness": "The nominal added B2 dose of 1.0 mg/day was verified. Actual intake, adherence, and treatment changes are a separate area of unverified information under N11; verification of the nominal dose does not replace verification of these details.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Corrections to Ma’s supplementation doses by arm, or records of actual administration." }, { "item_id": "N08", "question_type": "Shared iron and folate", "question": "Have the shared iron and folate in IFB and IF, and the excluded combination arms, been fixed?", "needed": "Corrections to the shared treatment in IFB/IF, records of actual concomitant treatment/changes, and information on arm composition.", "role": "Required", "role_reason": "The criteria concerning shared iron and folate must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information on shared iron and folate with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Fix the question as a comparison differing only in B2 on top of the same iron 60 mg/day and folic acid 400 μg/day. Do not transfer results from an arm that also adds vitamin A.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3 and M08 §8.2.2–8.2.3; internal application — an internal adaptation for shared iron and folate.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the component tables for the four arms, and review the extent to which the shared treatment was maintained and B2 was the only difference.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The comparator receives the same iron 60 mg/day and folic acid 400 μg/day. Select IFB versus IF, with only B2 added to shared iron and folate, and exclude arms that also add vitamin A.", "condition_status": "Met", "status_reason": "The nominal shared treatment and the definition of the comparison in terms of added components were verified in the original treatment descriptors (facets) and manuscript. Actual adherence remains separately unverified.", "missingness": "The nominal comparison was verified as adding only B2 to the same iron 60 mg/day and folic acid 400 μg/day. Actual intake, changes in concomitant treatment, and total exposure remain unverified under N11.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Corrections to the shared treatment in IFB/IF, records of actual concomitant treatment/changes, and information on arm composition." }, { "item_id": "N09", "question_type": "Duration of the principal comparison", "question": "Is supplementation in the principal IFB/IF question given for 2 months?", "needed": "Corrections to the duration of Ma’s principal comparison, and the measurement schedule.", "role": "Required", "role_reason": "The criteria concerning the duration of the principal comparison must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information on the duration of the principal comparison with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Link the 2-month duration of the principal comparison to the original data structure, and distinguish it from longer-term and postpartum follow-up.", "basis": "M03 §3.2.4 and M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed — an internal adaptation for the duration of the principal comparison.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the start and end of administration with the timing of Hb measurements to distinguish the nominal 2 months from the actual observation period.", "current_reports": [ "S23", "S24" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The duration of the principal question is verified as a duration value (amount) of 2, measured in months (unit). Longer-term and postpartum persistence remain unverified, and the 60 days in another study are not automatically merged as the same analysis time point.", "condition_status": "Met", "status_reason": "The original data structure verifies the principal duration as 2 months, so the criterion for identifying that narrowly defined duration is met.", "missingness": "The 2-month supplementation period in the principal comparison was verified. The complete actual Hb measurement schedule remains unverified under N12, and the 2 months are not extended to imply verification of longer-term or postpartum effects.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Corrections to the duration of Ma’s principal comparison, and the measurement schedule." }, { "item_id": "N10", "question_type": "Allocation and blinding", "question": "Have Ma’s random sequence, allocation concealment, and blinding procedures been verified?", "needed": "Ma’s random sequence, allocation concealment and blinding methods, and baseline table by arm.", "role": "Required", "role_reason": "The criteria concerning allocation and blinding must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information on allocation and blinding with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Verify random sequence generation, concealment, blinded assessment, and baseline balance for the relevant IFB/IF comparison.", "basis": "M08 §8.1–8.2.3; internal application — an internal adaptation for allocation and blinding.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the methods and baseline table of the four-arm trial to distinguish the stated design from actual procedures, and retain the areas that cannot be verified.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "Ma’s study is preserved as a randomized, double-blind, four-arm trial. The current summary does not contain details of sequence generation, allocation concealment, or blinded assessment, or complete information on baseline balance.", "condition_status": "Partly verified", "status_reason": "The design type was verified, but the detailed allocation and measurement procedures have not been verified.", "missingness": "The design type was verified as a randomized, double-blind, four-arm trial. The detailed procedures for sequence generation, allocation concealment, and blinded assessment, and complete information on baseline balance between arms, remain unverified.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Ma’s random sequence, allocation concealment and blinding methods, and baseline table by arm." }, { "item_id": "N11", "question_type": "Adherence and changes in concomitant treatment", "question": "Have actual adherence, rescue treatment, and total exposure in IFB/IF been verified?", "needed": "Records by arm of intake/adherence, rescue treatment, changes to iron/folate, diet, and other supplements.", "role": "Required", "role_reason": "The criteria concerning adherence and changes in concomitant treatment must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information on adherence and changes in concomitant treatment with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Link actual intake, deviations, changes in concomitant treatment, total dietary/supplement exposure by arm, and the methods used to handle these.", "basis": "M03 §3.2.3 and M08 §8.2.2–8.2.3; internal application; M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed — an internal adaptation for adherence and changes in concomitant treatment.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Review changes in administration and concomitant treatment over time, and compare the scope of analyses of the effect of assignment with that of analyses of the effect of actual intake.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "Shared iron and folate and the added B2 dose define the nominal comparison. Total dietary intake and exposure to all supplements are blank/unverified, and adherence and rescue-treatment information by arm could not be verified in the current summary either.", "condition_status": "Unverified", "status_reason": "The nominal doses and shared treatment alone do not establish that actual exposure or changes by arm have been verified.", "missingness": "Actual intake, adherence, rescue treatment, changes to iron and folate, and total dietary and other-supplement exposure by arm in IFB/IF remain unverified. Nominal doses and shared treatment alone cannot verify actual exposure.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Records by arm of intake/adherence, rescue treatment, changes to iron/folate, diet, and other supplements." }, { "item_id": "N12", "question_type": "Hb measurement", "question": "Have the Hb measurement methods, units, time points, and assessment procedures in IFB/IF been verified?", "needed": "Ma’s Hb assay methods, units, baseline/end-of-treatment measurement table, and information on blinded assessment.", "role": "Required", "role_reason": "The criteria concerning Hb measurement must be verified separately for this IFB versus IF question to avoid mixing results from other populations, combined formulations, or denominators.", "application_exception": "Do not fill gaps in unverified information on Hb measurement with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Link the actual assay methods, time points, baseline/end-of-treatment values, and assessment procedures for changes in blood Hb to the relevant result.", "basis": "M03 §3.2.4 and M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a and M03 §3.2.4; internal application — an internal adaptation for Hb measurement.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the Hb measurement procedures with the time points and units in the results tables, and keep them separate from anemia prevalence or other laboratory values.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The selected endpoint is the between-group difference in the change in blood Hb concentration. Anemia prevalence was also reported, but it does not replace this question. The actual Hb assay, measurement schedule, and complete assessment procedures remain unverified.", "condition_status": "Partly verified", "status_reason": "The endpoint's identity is linked, but the original methods and tables needed to verify the actual measurement conditions are still required.", "missingness": "The endpoint of change in blood Hb concentration has been verified, but the actual Hb assay, units, baseline and final measurement schedule, and complete assessment procedures remain unverified. Anemia prevalence is not substituted for this outcome.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Ma’s Hb assay methods, units, baseline/end-of-treatment measurement table, and information on blinded assessment." }, { "item_id": "N13", "question_type": "Effect of interest and analysis", "question": "Have the actual analysis population, adjustment, and definition of change for IFB versus IF been verified?", "needed": "The IFB/IF analysis plan, ITT/PP populations, adjustment model, definition of change, and original results tables.", "role": "Required", "role_reason": "The conditions concerning the effect of interest and analysis must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on the effect of interest and analysis with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Link the analytical definitions of the effect of assignment or adherence, ITT/PP, adjustment, and baseline/final values or change to the actual IFB/IF results.", "basis": "M08 §8.2.2, M15 §15.3.1; application for this sheet; M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to individual questions were designed for this sheet — an adaptation for this sheet concerning the effect of interest and analysis.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the reported analysis with the plan and review the scope of the estimate, without turning a within-group rise into a between-group effect of adding B2.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The question concerns the between-group difference in Hb change, but the corresponding IFB/IF effect size and dispersion remain unverified. Because complete paired-data or adjustment inputs were unavailable, the original record of effect-size attempts (effect_size_attempts) also produced no new approximation. The actual ITT/PP population or model is not filled in.", "condition_status": "Unverified", "status_reason": "The actual analytical definition for the principal comparison has not been verified, so it cannot be replaced with assignment counts or arithmetic from another comparison.", "missingness": "The IFB/IF analysis populations, such as ITT and PP, the adjustment model, and the actual definition of Hb change remain unverified. The required paired-data or adjustment inputs and the principal comparison's results table could not be verified either.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "The IFB/IF analysis plan, ITT/PP populations, adjustment model, definition of change, and original results tables." }, { "item_id": "N14", "question_type": "Allocation and analysis denominators", "question": "Have the 366 participants assigned overall and the 91/93 assigned to the two arms been linked to the actual Hb analysis denominators?", "needed": "Ma's IFB/IF participant flow diagram, measurement and analysis counts (n), reasons for exclusion, and table of missing-data handling.", "role": "Required", "role_reason": "The conditions concerning allocation and analysis denominators must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on allocation and analysis denominators with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Link recruitment → allocation to four arms → Hb measurement → analysis denominators, together with exclusions and missing-data handling, separately for IFB and IF.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for individual study designs were designed for this sheet; M08 §8.2.2, M15 §15.3.1; application for this sheet — an adaptation for this sheet concerning allocation and analysis denominators.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the total across the four arms with the participant flow in the two comparison arms, and check that the original total of 184 participants is not used as the analysis denominator.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "There were 366 participants assigned overall: IFB 91 and IF 93. The original descriptive total of 184 refers to assigned participants, not the endpoint analysis count (assigned_participants/not_analyzed_endpoint_n). The value field for the Hb analysis denominator is empty/unverified.", "condition_status": "Partly verified", "status_reason": "The assignment counts have been preserved, but they have not been linked to the corresponding Hb measurement and analysis counts (n) or to the flow of missing data.", "missingness": "The assignment counts of 366 overall, IFB 91, and IF 93 have been verified. The numbers with Hb measurements and included in analysis by arm, reasons for exclusion, and missing-data handling remain unverified; the historical total of 184 is not used as the Hb analysis denominator.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Ma's IFB/IF participant flow diagram, measurement and analysis counts (n), reasons for exclusion, and table of missing-data handling." }, { "item_id": "N15", "question_type": "Hb difference from adding B2 alone", "question": "Has the between-group Hb effect size for IFB versus IF been verified?", "needed": "Ma's Hb values by IFB/IF arm, between-group estimate, definitions, and original tables.", "role": "Required", "role_reason": "The conditions concerning the Hb difference from adding B2 alone must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on the Hb difference from adding B2 alone with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Verify the original between-group Hb effect size, units, and definition of the estimate for the comparison that adds only B2 to the same iron and folate treatment.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to individual questions were designed for this sheet; M08 §8.2.2, M15 §15.3.1; application for this sheet; M15 §15.3.1–15.3.3; application for this sheet — an adaptation for this sheet concerning the Hb difference from adding B2 alone.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the original results tables for the four arms, extract only the estimate for the principal IFB/IF comparison, and exclude values for the combination arm or prevalence.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The IFB–IF Hb effect size and dispersion remain unverified in the currently accessible materials. EX denotes this verification limit; it does not mean an effect of 0 or that data are absent from the entire full text that could not be accessed.", "condition_status": "Unverified", "status_reason": "The inputs needed to verify the effect value for the principal comparison of adding B2 alone are unavailable.", "missingness": "The materials needed to verify the original between-group Hb effect size, units, and definition of the estimate for IFB versus IF, which adds only B2, remain unverified. EX denotes the limits of current access; it does not mean an effect of 0 or that data are absent from the entire full text.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Ma's Hb values by IFB/IF arm, between-group estimate, definitions, and original tables." }, { "item_id": "N16", "question_type": "Dispersion and intervals", "question": "Have the type of dispersion measure, CI, and criterion for an important difference for IFB/IF been verified?", "needed": "Original information on the type of dispersion measure, CI, analysis count (n), and a justified important Hb difference for the principal IFB/IF comparison.", "role": "Required", "role_reason": "The conditions concerning dispersion and intervals must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on dispersion and intervals with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Verify the type of measure, such as SD/SE, the analysis count (n), and CI for the principal estimate, together with a justified criterion for an important Hb difference.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for individual study designs were designed for this sheet; M15 §15.3.1–15.3.3; application for this sheet — an adaptation for this sheet concerning dispersion and intervals.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the original table footnotes, analysis model, and intervals, and review the scope of interpretation by comparing them with the defined important difference.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The IFB–IF Hb difference, dispersion, interval, and denominator remain unverified. The original CX is preserved, and the ±1.1 from another combination arm is not filled in as SD/SE or a CI. No arbitrary minimum sample size or important difference is created.", "condition_status": "Unverified", "status_reason": "The original inputs for the precision of the principal comparison and the criterion for importance have not been verified.", "missingness": "The type of dispersion measure, analysis count (n), and CI for the principal IFB/IF effect, together with an evidence-based criterion for an important Hb difference, remain unverified. The ±1.1 from the IFAB combination arm is not substituted for the SD, SE, or CI of the principal comparison.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Original information on the type of dispersion measure, CI, analysis count (n), and a justified important Hb difference for the principal IFB/IF comparison." }, { "item_id": "N17", "question_type": "Attribution of the combination-arm value", "question": "Has 5.4±1.1 g/L been excluded from the effect of adding B2 alone?", "needed": "Original tables and footnotes that correct the attribution of results to the combination or single-addition arm, or the type of measure represented by ±.", "role": "Required", "role_reason": "The conditions concerning attribution of the combination-arm value must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on attribution of the combination-arm value with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Attribute 5.4±1.1 g/L to IFAB versus IF, in which A+B2 are added together; do not repurpose it as an effect of B2 alone or as an identified type of dispersion measure.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses was designed for this sheet; M03 §3.2.2–3.2.3; reverse-direction markers and adaptations of checks were designed for this sheet; M03 §3.2.3, M08 §8.2.2–8.2.3; application for this sheet — an adaptation for this sheet concerning attribution of the combination-arm value.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the components and results of the four arms side by side, and verify the comparison arms and definition of dispersion for each number.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The abstract's 5.4±1.1 g/L is for IFAB versus IF, which adds both vitamin A and B2. The original correction excluded it from the effect of adding B2 alone and did not fill in an SD/SE designation absent from the abstract.", "condition_status": "Met", "status_reason": "The original attribution of the combination-arm number and the unverified type of dispersion measure have been preserved in the current manuscript and correction.", "missingness": "The attribution of 5.4±1.1 g/L to IFAB versus IF, which adds A and B2 together, has been verified. The type of dispersion measure represented by ± remains unverified in the abstract, and the number is not repurposed as an effect value for B2 alone.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Original tables and footnotes that correct the attribution of results to the combination or single-addition arm, or the type of measure represented by ±." }, { "item_id": "N18", "question_type": "Registration and analysis plan", "question": "Are Ma's Hb endpoint, time points, and analysis consistent with the prospective registration and plan?", "needed": "Ma's registration, protocol, SAP, change history, and original Hb results.", "role": "Required", "role_reason": "The conditions concerning registration and the analysis plan must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on registration and the analysis plan with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Compare the reported information with the endpoint status, time points, and analysis specified in the registration, protocol, and SAP for the principal comparison.", "basis": "M08 Table 8.2.a, M04 §4.6.3; application for this sheet — an adaptation for this sheet concerning registration and the analysis plan.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the status of Hb in the original plan with the actual IFB/IF report, leaving anything that cannot be cross-checked unverified.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "Ma's trial registration identifier field (nct) is empty, and the value field in the record of the registered primary endpoint and the value comparing the study's primary endpoint with this page's endpoint (study_primary_vs_page_endpoint.value) are also empty/unverified. The fact that Hb is a reported endpoint is not converted into designation as the registered primary (1st) endpoint.", "condition_status": "Unverified", "status_reason": "Independent materials for cross-checking the plan and registration are unavailable, so concordance, nonregistration, or selective reporting cannot be established.", "missingness": "Independent cross-checking of Ma's registration identity, protocol, SAP, and the Hb endpoint's status, time points, analysis, and change history remains unverified. An empty nct field is not interpreted as confirmation of nonregistration or selective reporting.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Ma's registration, protocol, SAP, change history, and original Hb results." }, { "item_id": "N19", "question_type": "Suprapto comparison values", "question": "Have Suprapto's between-group Hb values for B2 versus iron and folate been verified?", "needed": "Suprapto's arm composition, Hb results for B2 versus iron/folate, dispersion/CI, and analysis count (n).", "role": "Required", "role_reason": "The conditions concerning Suprapto's comparison values must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on Suprapto's comparison values with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Link the actual comparison values and intervals for B2 versus iron and folate, with alternating allocation and 5 mg/60 days, to the corresponding population and denominators.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses was designed for this sheet; M08 §8.1–8.2.3; application for this sheet; M04 §4.6.1–4.6.2, M15 §15.3.1; application for this sheet — an adaptation for this sheet concerning Suprapto's comparison values.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the original results by arm with the significant comparison in the abstract, distinguishing B2 versus vitamin A results from results versus iron and folate.", "current_reports": [ "S24" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "Suprapto's study used alternating allocation and 5 mg for 60 days. The significant comparison in the abstract is the B2 arm versus the vitamin A arm; it does not establish an effect of B2 versus iron and folate. It is not directly pooled with Ma's randomized comparison of 1 mg for 2 months.", "condition_status": "Unverified", "status_reason": "Although related materials on anemia in pregnancy are available, the between-group Hb values for the target comparison remain unverified in the current summary.", "missingness": "Suprapto's between-group Hb values, dispersion, CI, and actual analysis count (n) for B2 versus iron and folate remain unverified. The significant comparison of B2 versus vitamin A presented in the abstract does not verify the target comparison.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Suprapto's arm composition, Hb results for B2 versus iron/folate, dispersion/CI, and analysis count (n)." }, { "item_id": "N20", "question_type": "Suprapto exclusion flow", "question": "Have the reasons by arm for excluding 19 of 103 participants and the Hb analysis denominators been verified?", "needed": "Suprapto's allocation/exclusion/analysis flow by arm, reasons for excluding 19 participants, and missing-data handling.", "role": "Required", "role_reason": "The conditions concerning Suprapto's exclusion flow must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on Suprapto's exclusion flow with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Link the total assigned by alternating allocation, reasons for exclusion by arm, actual Hb analysis counts (n), and handling methods.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for individual study designs were designed for this sheet; M08 §8.1–8.2.3; application for this sheet — an adaptation for this sheet concerning Suprapto's exclusion flow.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Review the original flow diagram to verify the distribution by arm of the 19 excluded participants and the originally reported 18.4%; do not generate an analysis count (n) by totaling the remaining participants.", "current_reports": [ "S24" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "Preserve the alternating allocation of 103 participants, the exclusion of 19 from analysis, and the originally reported 18.4%. The check of 18.4% in the original numerical-check record (numeric_checks) is a historical record and is not recalculated in this work. Hb denominators by arm and reasons for exclusion remain unverified.", "condition_status": "Partly verified", "status_reason": "The overall assignment count and the reported number excluded are available, but the analysis flow by arm has not been verified.", "missingness": "The alternating allocation of 103 participants, the exclusion of 19, and the originally reported 18.4% have been preserved. Allocation, exclusion, and Hb analysis flow by arm, reasons for exclusion, and missing-data handling remain unverified.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Suprapto's allocation/exclusion/analysis flow by arm, reasons for excluding 19 participants, and missing-data handling." }, { "item_id": "N21", "question_type": "RIBOFEM as one study family", "question": "Do the S10 protocol and the S11 results citation belong to the same RIBOFEM study family?", "needed": "Original bibliographic and registration materials that correct the identity relationship between the RIBOFEM protocol and results.", "role": "Required", "role_reason": "The conditions concerning RIBOFEM as one study family must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on RIBOFEM as one study family with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Link the preserved study identifier (study_id) and relationships, so that the protocol and results reports are not counted as new independent trials.", "basis": "M04 §4.6.1–4.6.2 on distinguishing studies from reports; cohort/outcome linkage is an application for this sheet; M04 §4.6.1–4.6.2, M15 §15.3.1; application for this sheet — an adaptation for this sheet concerning RIBOFEM as one study family.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Cross-check the protocol/results linkage using registration, authorship, and recruitment information; do not count reports from the same study family as separate trials.", "current_reports": [ "S10", "S11" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The study identifier (study_id) for S10 and S11 is RIBOFEM. S10 is a protocol involving healthy women with low B2 status, and S11 is the results citation for the same study family, with full-text effect values unverified. The 2 reports are not newly counted as 2 trials.", "condition_status": "Met", "status_reason": "The original study identifier (study_id) and report role (role) specify the shared study family and the difference in report types.", "missingness": "The linkage of the S10 protocol and the S11 results citation to the same RIBOFEM study family has been verified. The actual full-text effect values for S11 remain unverified, and the two reports are not counted as two independent trials.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Original bibliographic and registration materials that correct the identity relationship between the RIBOFEM protocol and results." }, { "item_id": "N22", "question_type": "Healthy women and design assumptions", "question": "Have the healthy women with low B2 status and the Hb assumptions for sample-size planning been excluded from observed treatment effects?", "needed": "Original materials that correct the attribution of RIBOFEM's actual results, population, and design assumptions.", "role": "Required", "role_reason": "The conditions concerning healthy women and design assumptions must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on healthy women and design assumptions with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Do not use RIBOFEM's selection of healthy women and sample-size planning assumptions as actual IFB/IF treatment effects in anemic pregnant women.", "basis": "M03 §3.2.1; detailed population conditions were designed for this sheet; M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to individual questions were designed for this sheet; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses was designed for this sheet; M04 §4.6.1–4.6.2, M15 §15.3.1; application for this sheet — an adaptation for this sheet concerning healthy women and design assumptions.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the protocol assumptions with the results tables to separate the Hb difference used for planning from observed values, and reassess the direct relevance of the population.", "current_reports": [ "S10", "S11" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "RIBOFEM involves healthy young women with low B2 status. The Hb difference used for sample-size planning was not used as an observed treatment effect, and no unverified numerical effect values for S11 were created.", "condition_status": "Met", "status_reason": "The exclusion boundaries for the population, design assumptions, and unverified results were verified in the preserved original results/bibliographic records.", "missingness": "The boundary that prevents RIBOFEM's population of healthy women with low B2 status and Hb assumptions for sample-size planning from being repurposed as treatment effects for anemia in pregnancy has been verified. The actual numerical effect values for S11 remain unverified.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Original materials that correct the attribution of RIBOFEM's actual results, population, and design assumptions." }, { "item_id": "N23", "question_type": "Direct replication", "question": "Has the same IFB/IF question been replicated in a separate independent study family?", "needed": "Population, product, dose, duration, IFB/IF Hb results, and study-family linkage information for an independent trial.", "role": "Required", "role_reason": "The conditions concerning direct replication must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on direct replication with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Link actual results from an independent study family that is eligible in terms of the same population, addition of B2 alone, duration/dose, and Hb analysis.", "basis": "M04 §4.6.1–4.6.2 on distinguishing studies from reports; cohort/outcome linkage is an application for this sheet; M04 §4.6.1–4.6.2, M15 §15.3.1; application for this sheet — an adaptation for this sheet concerning direct replication.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare distinct study families and comparison conditions to assess whether reports with other doses/designs or healthy women are exact replications.", "current_reports": [ "S23", "S24", "S10", "S11" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The original R1 refers to Ma's decisive trial supporting the principal comparison. Suprapto's different dose and alternating allocation, and RIBOFEM's different population and reports from the same study family, were not verified as independent replications of the exact principal comparison.", "condition_status": "Unverified", "status_reason": "Independent replication of the exact add-on question has not been verified in this input, and the number of reports is not substituted for the number of replications.", "missingness": "It remains unverified whether the principal IFB/IF comparison has been replicated in a separate independent study family with the same population, addition of B2 alone, dose, duration, and Hb analysis conditions. The number of related reports is not substituted for direct replication.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Population, product, dose, duration, IFB/IF Hb results, and study-family linkage information for an independent trial." }, { "item_id": "N24", "question_type": "Funding and interests", "question": "Have funding, product provision, and author interests been verified for each relevant report?", "needed": "Original declarations of funding, product provision, and conflicts of interest (COI) for each Ma/Suprapto/RIBOFEM report.", "role": "Supplementary; required for independence claims", "role_reason": "The conditions concerning funding and interests must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified information on funding and interests with another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Verify the actual funding, provision, and author declarations for each report and its study-family relationships at the recorded source locations.", "basis": "Chamgap's own conditions for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items — an adaptation for this sheet concerning funding and interests.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare each report's declarations with institutional support and product provision, without concluding that unverified funding is independent funding or evidence of bias.", "current_reports": [ "S23", "S24", "S10", "S11" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The funding information for the 4 evidence entries is preserved as unverified or not used in this page's grade. Distinguish the original treatment under I1/precedent 29 from actual verification of independent funding.", "condition_status": "Unverified", "status_reason": "The original I1 axis alone does not verify funding, product provision, or conflicts of interest (COI) for each report.", "missingness": "The actual declarations of research funding, product provision, and author and institutional interests for each Ma, Suprapto, and RIBOFEM report remain unverified. The original I1 treatment does not mean that independent funding has been verified.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Original declarations of funding, product provision, and conflicts of interest (COI) for each Ma/Suprapto/RIBOFEM report." }, { "item_id": "N25", "question_type": "Extension to the optimal dose", "question": "Does this Hb question require a judgment on the optimal dose of 1 mg versus 5 mg?", "needed": "If a separate dose comparison is reviewed: a direct randomized comparison of doses in the same population, with its plan and results.", "role": "Conditional; required when extending the question to dose comparisons", "role_reason": "The conditions concerning an extension to the optimal dose must be checked separately for this IFB versus IF question, so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Proof of the optimal dose is not imposed as a requirement for the narrow question of adding 1 mg.", "criterion": "Preserve the current question of adding 1 mg, and do not remove that narrow question because a separate dose comparison is unavailable.", "basis": "M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification were designed for this sheet — an adaptation for this sheet concerning an extension to the optimal dose.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "If the extended question is approved, review a randomized comparison of doses in the same population with Hb and harms predefined for each dose.", "current_reports": [ "S23", "S24" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The Ma 1 mg and Suprapto 5 mg materials concern different study designs, populations, and comparison conditions. These differences are not used to judge the optimal dose or dose–response, and an optimal-dose trial is not imposed on the current 1 mg question.", "condition_status": "Not applicable", "status_reason": "The optimal dose is a separate extension requirement outside the narrow principal question. The unverified status of direct comparison data remains recorded in the observations.", "missingness": "The optimal dose is not applicable to the current narrow question of adding 1 mg. Ma 1 mg and Suprapto 5 mg have not been verified as a direct dose comparison in the same population, and no judgment is made about the optimal dose or dose–response.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "If a separate dose comparison is reviewed: a direct randomized comparison of doses in the same population, with its plan and results." }, { "item_id": "N26", "question_type": "Extension to postpartum effects and persistence", "question": "Does this question require a judgment on persistence beyond 2 months or on postpartum effects?", "needed": "If the question is extended to persistence: denominators and time points for Hb after treatment discontinuation, postpartum, and over the long term, together with separate plans and results.", "role": "Conditional; required for an extension to persistence", "role_reason": "The conditions for an extension to postpartum effects and persistence must be checked separately for this IFB versus IF question so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not impose evidence of long-term maintenance as a requirement for the 2-month effect question.", "criterion": "Distinguish the principal 2-month comparison from separate questions about the long term, discontinuation, or the postpartum period.", "basis": "M03 §3.2.1–3.2.4; the details concerning dose, persistence, and effect modification were developed for this assessment — an adaptation for the extension to postpartum effects and persistence.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "For an extended question, review designs that distinguish the end of treatment, discontinuation, and postpartum time points while tracking Hb and changes in the shared treatment.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The original duration is 2 months, and long-term and postpartum persistence remain unverified. Do not add a long-term maintenance trial as a mandatory requirement for the narrow principal question covering 2 months.", "condition_status": "Not applicable", "status_reason": "Efficacy during maintenance or postpartum is a separate question outside the scope of the current comparison.", "missingness": "Long-term maintenance efficacy, efficacy after discontinuation, or postpartum efficacy is not applicable to the current 2-month comparison. These extended effects remain unverified and are distinguished from verification of the principal comparison's duration.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "If the question is extended to persistence: denominators and time points for Hb after treatment discontinuation, postpartum, and over the long term, together with separate plans and results." }, { "item_id": "N27", "question_type": "Hb and clinical events", "question": "Does the Hb question require evidence of benefit for maternal and fetal clinical events?", "needed": "If the question is extended to clinical events: definitions of maternal/fetal events, denominators, follow-up, and results of the planned comparisons.", "role": "Conditional; required for an extension to clinical events", "role_reason": "The conditions concerning Hb and clinical events must be checked separately for this IFB versus IF question so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not impose a clinical-event trial as a requirement for a question about the Hb value itself.", "criterion": "Separate the question about change in Hb values from questions about clinical events, quality of life, mortality, or birth outcomes.", "basis": "M03 §3.2.4; limits on extensions were developed for this assessment; M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to each question were developed for this assessment — an adaptation for Hb and clinical events.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "For an extended question, define maternal/fetal events as endpoints separate from Hb and review the relevant direct comparison and follow-up.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "Hb is the original surrogate laboratory endpoint, designated S. Do not extend it to confirmation of clinical-event prevention or safety, and do not impose a clinical-event trial on the Hb comparison itself.", "condition_status": "Not applicable", "status_reason": "The current single question concerns Hb change; benefit in clinical events is a separate extension. Unverified harms remain unverified under the following safety conditions.", "missingness": "Benefit in maternal/fetal clinical events is not applicable to the current question about Hb change. Do not extend the Hb endpoint to confirmation of clinical-event prevention; the unverified status of harm information is retained separately in N28·N29.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "If the question is extended to clinical events: definitions of maternal/fetal events, denominators, follow-up, and results of the planned comparisons." }, { "item_id": "N28", "question_type": "Collection of harms by arm", "question": "Have the definitions of adverse events and discontinuation, and the denominators for each IFB/IF arm, been verified?", "needed": "Ma IFB/IF harm-collection methods; tables of adverse events (AE), serious adverse events (SAE), and discontinuations; participant/event counts; and denominators and follow-up by arm.", "role": "Supplementary; required for comparative safety claims", "role_reason": "The conditions for collection of harms by arm must be checked separately for this IFB versus IF question so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified data on collection of harms by arm using another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Verify event/participant counts, systematic collection, severity, discontinuations, exposure and analysis denominators by arm, and duration.", "basis": "M19 §19.1.2–19.2.4; application developed for this assessment; M19 §19.1.2–19.2.4; detailed distinctions were developed for this assessment; M19 §19.2.2–19.2.4, M03 §3.2.3; application developed for this assessment; M19 §19.1.2–19.2.4, M04 §4.6.3; application developed for this assessment — an adaptation for collection of harms by arm.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Distinguish events from participants in the original harm tables, compare follow-up and discontinuations by arm, and do not convert unreported or unobtained data into 0 events.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "Adverse-event denominators by arm and long-term maternal/fetal outcomes remain unverified in the accessed materials. Do not derive a claim of safety, AE 0, or risk rates solely from the existence of a study in pregnant women or the allocation of 91/93 participants.", "condition_status": "Unverified", "status_reason": "Harm collection, aggregation, and denominators cannot be verified from the current input.", "missingness": "For the same IFB/IF exposures, adverse-event definitions, collection methods, severity, discontinuations, numbers of participants with events and numbers of events, and denominators and follow-up by arm remain unverified. Do not derive a claim of safety, AE 0, or risk rates from the allocation of 91/93 participants.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Ma IFB/IF harm-collection methods; tables of adverse events (AE), serious adverse events (SAE), and discontinuations; participant/event counts; and denominators and follow-up by arm." }, { "item_id": "N29", "question_type": "Pregnancy and long-term safety", "question": "Have long-term maternal/fetal harms and their timing in relation to exposure been verified?", "needed": "Exposure by stage of pregnancy; timing of maternal/fetal event onset and discontinuation; and long-term follow-up results.", "role": "Supplementary; required for an extension to pregnancy safety", "role_reason": "The conditions for pregnancy and long-term safety must be checked separately for this IFB versus IF question so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified pregnancy and long-term safety data using another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Verify the stage of pregnancy, exposure/event onset, long-term maternal/fetal follow-up, and the actual scope of event reporting.", "basis": "M19 §19.1.2–19.2.4; application developed for this assessment; harm questions by study design in M19 §19.2; details of temporal relationships were developed for this assessment; Chamgap's own limits on interpretation. This draws on M19 principles and is not an application of an official causality tool — an adaptation for pregnancy and long-term safety.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the stage of pregnancy with the exposure timeline, and review rare events and fetal outcomes separately with appropriate long-term follow-up.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "Long-term maternal/fetal outcomes remain unverified in the materials accessed in this work. No conclusion is drawn about safety across all doses and formulations, and this is not advice to stop or replace the shared iron–folate treatment.", "condition_status": "Unverified", "status_reason": "A short Hb comparison and pregnancy exposure alone cannot establish long-term safety or safety at other doses.", "missingness": "Actual exposure by stage of pregnancy, the timing of maternal/fetal event onset and discontinuation, and long-term follow-up results remain unverified. Do not establish long-term safety across all doses and formulations from a short Hb comparison.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Exposure by stage of pregnancy; timing of maternal/fetal event onset and discontinuation; and long-term follow-up results." }, { "item_id": "N30", "question_type": "Assay interference", "question": "Has Hb assay interference for this question been checked separately?", "needed": "The actual Hb assay method, data on testing for B2 interference, and search records for that scope.", "role": "Supplementary; needed to interpret measurements", "role_reason": "The conditions for assay interference must be checked separately for this IFB versus IF question so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified assay-interference data using another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Distinguish the scope in which interference between the Hb assay method and B2 exposure was directly checked from areas that were not searched.", "basis": "M08 Table 8.2.a, M03 §3.2.4; application developed for this assessment; design considerations in M19 §19.2.2–19.2.4; detailed records of confounding were developed for this assessment — an adaptation for assay interference.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the original assay with interference experiments, and review clinical Hb change and the possibility of analytical interference separately.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The assay-interference value field (assay_interference.value) is empty, and no separate search was conducted. The absence of a separate systematic search does not establish the absence of interference. No additional external interference materials are being read in this work either.", "condition_status": "Unverified", "status_reason": "There is no record of a separate interference check having been performed, nor are the corresponding direct materials available.", "missingness": "B2 interference data for the actual Hb assay method and the scope of any separate systematic verification remain unverified. Do not turn the original absence of a separate search into a finding of no interference.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "The actual Hb assay method, data on testing for B2 interference, and search records for that scope." }, { "item_id": "N31", "question_type": "Limits concerning drugs and concomitant use", "question": "Have drug interactions beyond the shared treatment been comprehensively verified?", "needed": "Participants' complete lists of concomitant treatments; interaction/exposure data; and the original search scope.", "role": "Supplementary; required for an extension to safety of concomitant use", "role_reason": "The conditions concerning limits on drugs and concomitant use must be checked separately for this IFB versus IF question so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified data on the limits concerning drugs and concomitant use using another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Link the scope of verification and searches concerning concomitant drug/supplement use and interactions to the actual records.", "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; application developed for this assessment; M19 §19.1.2–19.2.4; application developed for this assessment; design considerations in M19 §19.2.2–19.2.4; detailed records of confounding were developed for this assessment — an adaptation for limits concerning drugs and concomitant use.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare concomitant use and actual exposure by arm, and review drug-interaction data and areas not searched separately.", "current_reports": [ "S23" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The drug-interaction field (drug_interactions) is empty, and no separate search was conducted; no separate comprehensive search of all drug interactions was performed. Total intake also remains unverified. Do not turn a nominal comparison of the shared iron–folate treatment into comprehensive verification of interactions.", "condition_status": "Unverified", "status_reason": "Identifying some concomitant treatments and verifying all drug interactions are different scopes of work.", "missingness": "Participants' complete concomitant drug and supplement use and data on specific interactions remain unverified. No separate comprehensive search was performed, and verification of the nominal identity of the shared iron–folate treatment does not substitute for that scope of work.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Participants' complete lists of concomitant treatments; interaction/exposure data; and the original search scope." }, { "item_id": "N32", "question_type": "Current and historical reading", "question": "Has reading the summaries in this work been distinguished from each report's historical access and from the fact that external materials have not been read in this work?", "needed": "Corrections to each report's original access record/access date, link, and material type, or an actual material-acquisition event.", "role": "Required", "role_reason": "The conditions for current and historical reading must be checked separately for this IFB versus IF question so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified data on current and historical reading using another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Record the actual reading of the currently retained summaries and, for each external material, that access was not attempted and the material was neither obtained nor read in this work; preserve historical access levels and original locations separately.", "basis": "Material-collection and selection principles in M04 §4.5–4.6; the distinction between access and reading and the rules governing hyperlinks were developed for this assessment; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were developed for this assessment — an adaptation for current and historical reading.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare each report's citation record (citation) with its access history, link the summary viewer (reader) to the original location, and record any actual reading of external materials only as a separate event.", "current_reports": [ "S23", "S24", "S10", "S11" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "This work involved actually reading the currently retained Korean/English (KO/EN) summaries. The original records for S23's indexed author abstract, S24's publisher abstract, S10's full-text HTML article, and S11's provided bibliographic extraction describe historical access. No access-date key exists for each citation record (citation), so these values are left empty; 2026-09-15 is distinguished as the original review date for the record as a whole. Access to the four external links was not attempted, and their materials were not read in this work.", "condition_status": "Met", "status_reason": "Current reading, material types, historical access, and the absence of individual access dates were distinguished in accordance with the actual input schema.", "missingness": "The distinction between reading the locally retained summaries in this work, each report's historical access, and the fact that external materials have not been read in this work was verified. Individual access dates were absent from the original citation records (citation) and were preserved as empty values; none of the four external materials was directly read in this work.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Corrections to each report's original access record/access date, link, and material type, or an actual material-acquisition event." }, { "item_id": "N33", "question_type": "Scope of searches and corrections", "question": "Have the original search cutoff, corrections, and the scope of activities not performed in this work been stated explicitly?", "needed": "Original search and selection/correction logs, or a new official correction or full-text acquisition event.", "role": "Required", "role_reason": "The conditions for the scope of searches and corrections must be checked separately for this IFB versus IF question so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified data on the scope of searches and corrections using another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Link the preserved search cutoff, revisions, and unverified items to the scope of new searches, full-text reading, and calculations not performed in this work.", "basis": "M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were developed for this assessment; M04 §4.6.3, M15 §15.3.1–15.3.3; distinctions between statuses were developed for this assessment — an adaptation for the scope of searches and corrections.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the original records of existing searches and corrections, and, if a new evidence review is separately approved, update them while recording dates, inclusion/exclusion decisions, and material levels.", "current_reports": [ "S23", "S24", "S10", "S11" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "The original search cutoff and verification date (search_cutoff/verified_date) are 2026-09-15. This was not an exhaustive search of primary databases worldwide; the preservation conversion recorded here is dated 2026-10-05. The separate original search log (search_log), numerical evidence file (numeric_evidence), and report files were not opened, and no new search or calculation was performed.", "condition_status": "Met", "status_reason": "The scope of preservation checks and the activities not performed in this work were stated explicitly, without converting an absence of searching into 0 human studies.", "missingness": "The original cutoff date, the limited scope of searches and corrections, and the activities not performed during this conversion were stated explicitly. The separate search log (search_log), numerical evidence file (numeric_evidence), and report files, as well as the latest external literature, were neither read nor searched in this work.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "Original search and selection/correction logs, or a new official correction or full-text acquisition event." }, { "item_id": "N34", "question_type": "Original judgment and historical values", "question": "Have the original C·46, all assessment axes, empty values, and historical arithmetic been preserved unchanged?", "needed": "An official correction concerning the original judgment, assessment axes, empty values, arithmetic, or sources/identity.", "role": "Required", "role_reason": "The conditions for the original judgment and historical values must be checked separately for this IFB versus IF question so that results from different populations, combination products, or denominators are not mixed.", "application_exception": "Do not fill gaps in unverified data on the original judgment and historical values using another study, allocation counts, or a different comparison in a title or abstract.", "criterion": "Preserve the current original grade and score (grade/score), assessment axes, statuses, all values in their original form, and historical arithmetic separately from any new assessment of conditions.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules were developed for this assessment; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were developed for this assessment — an adaptation for the original judgment and historical values.", "condition_origin": "Criteria developed for this case with knowledge of the original content. This is not a blinded or preregistered process or an officially certified assessment.", "proposed_research": "Compare the complete original text before and after a correction, link only the changed identities/values to their supporting evidence and dates, and distinguish revision of the conditions version from a new judgment.", "current_reports": [ "S23", "S24", "S10", "S11" ], "existence": "The identity of the currently preserved source summary (source) and its original locations/values have been checked; this is separate from obtaining external original source material.", "acquired_read": "Summary read: the currently preserved KO/EN summaries were actually read. The related external original source material was not read in this work.", "observation": "Preserve the original C·46, B/S/R1/I1/EX/B1/CX, and the flag indicating whether there are no human studies (no_human_study=false). The original allocation total of 184 and arithmetic check of 18.4% were read as historical descriptive values; no new calculations, efficacy/safety scores, or condition-fulfillment rates were created.", "condition_status": "Met", "status_reason": "Preservation of all values in their original form throughout the source was distinguished from the new table's unscored status. This is neither independent clinical certification nor a new judgment.", "missingness": "Preservation of the original C·46, assessment axes, empty values, and historical arithmetic was verified. This verification is neither independent certification of the original clinical values nor a new efficacy or safety judgment, and no new clinical calculations were performed in this work.", "uncertainty": "Original papers, registries, and older separate files outside the summaries preserved for this work were not read. An unverified status for this criterion is not interpreted as evidence of no effect.", "review_date": "2026-10-05", "reading_status": "Original papers unread · Preserved summaries read", "additional_material": "An official correction concerning the original judgment, assessment axes, empty values, arithmetic, or sources/identity." } ], "reports": [ { "report_id": "S23", "title": "Ma et al. — retinol/riboflavin added to iron and folate in anemic pregnant women (2008)", "url": "https://pubmed.ncbi.nlm.nih.gov/18806105/", "report_type": "Direct add-on comparison; actual route unverified", "existence": "Report identity and original URL in the retained bibliographic record", "acquired_read": "Summary reading: the currently preserved, retained summaries were actually read. Access to external original materials was not attempted, and they were neither obtained nor read in this work.", "study_family": "Ma-pregnancy-anemia-2008", "independent_replication": "Do not newly count the 4 reports as 4 unique trials or independent replications. Preserve the original R1 and each material's status as direct evidence, contextual evidence, or unverified.", "observed_result": "The IFB–IF Hb effect size and dispersion for adding B2 alone remain unverified. The total of 366, IFB 91, and IF 93 are allocation counts and must not be substituted for analysis denominators. The 5.4±1.1 g/L value belongs to the IFAB combination arm, and what the ± represents is unspecified.", "result_level": "Direct add-on comparison; actual route unverified", "materials": [ { "material_type": "PubMed article abstract and bibliographic page", "public_status": "Currently unverified", "access_status": "External access not attempted in this work", "acquired": false, "actually_read": "Unread", "as_of": "2026-10-05", "qualification": "Direct add-on comparison; actual route unverified; access to external original materials was not attempted, and they were neither obtained nor read in this work.", "material_id": "S23-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/18806105/" } ], "links": [ { "label": "Official source", "url": "https://pubmed.ncbi.nlm.nih.gov/18806105/" } ] }, { "report_id": "S24", "title": "Suprapto et al. — riboflavin added to iron–folate in anemic pregnant women (2002)", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1440-6047.2002.00310.x", "report_type": "Contextual evidence with a different dose, allocation method, and comparison", "existence": "Report identity and original URL in the retained bibliographic record", "acquired_read": "Summary reading: the currently preserved, retained summaries were actually read. Access to external original materials was not attempted, and they were neither obtained nor read in this work.", "study_family": "Suprapto-pregnancy-anemia-2002", "independent_replication": "Do not newly count the 4 reports as 4 unique trials or independent replications. Preserve the original R1 and each material's status as direct evidence, contextual evidence, or unverified.", "observed_result": "103 participants were alternately allocated; B2 was 5 mg for 60 days; 19 participants were excluded (originally reported as 18.4%). The significant comparison in the abstract was B2 versus vitamin A, and the between-arm Hb value for B2 versus iron–folate could not be verified.", "result_level": "Contextual evidence with a different dose, allocation method, and comparison", "materials": [ { "material_type": "Publisher's article abstract webpage", "public_status": "Currently unverified", "access_status": "External access not attempted in this work", "acquired": false, "actually_read": "Unread", "as_of": "2026-10-05", "qualification": "Contextual evidence with a different dose, allocation method, and comparison; access to external original materials was not attempted, and they were neither obtained nor read in this work.", "material_id": "S24-M1", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1440-6047.2002.00310.x" } ], "links": [ { "label": "Official source", "url": "https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1440-6047.2002.00310.x" } ] }, { "report_id": "S10", "title": "RIBOFEM protocol — riboflavin status and hematology in young women", "url": "https://link.springer.com/article/10.1186/1471-2458-9-90", "report_type": "Different population; study design, not observed results", "existence": "Report identity and original URL in the retained bibliographic record", "acquired_read": "Summary reading: the currently preserved, retained summaries were actually read. Access to external original materials was not attempted, and they were neither obtained nor read in this work.", "study_family": "RIBOFEM", "independent_replication": "Do not newly count the 4 reports as 4 unique trials or independent replications. Preserve the original R1 and each material's status as direct evidence, contextual evidence, or unverified.", "observed_result": "This is a protocol for healthy young women with low B2 status. Hb assumptions used for sample-size planning are not used as observed effects, and the protocol is excluded from direct evidence for anemic pregnant women.", "result_level": "Different population; study design, not observed results", "materials": [ { "material_type": "Full-text study protocol on the web (HTML)", "public_status": "Currently unverified", "access_status": "External access not attempted in this work", "acquired": false, "actually_read": "Unread", "as_of": "2026-10-05", "qualification": "Different population; study design, not observed results; access to external original materials was not attempted, and they were neither obtained nor read in this work.", "material_id": "S10-M1", "url": "https://link.springer.com/article/10.1186/1471-2458-9-90" } ], "links": [ { "label": "Official source", "url": "https://link.springer.com/article/10.1186/1471-2458-9-90" } ] }, { "report_id": "S11", "title": "Correcting marginal riboflavin deficiency and hematologic status in young UK women (2011)", "url": "https://pubmed.ncbi.nlm.nih.gov/21525198/", "report_type": "Result details unverified within the same trial family", "existence": "Report identity and original URL in the retained bibliographic record", "acquired_read": "Summary reading: the currently preserved, retained summaries were actually read. Access to external original materials was not attempted, and they were neither obtained nor read in this work.", "study_family": "RIBOFEM", "independent_replication": "Do not newly count the 4 reports as 4 unique trials or independent replications. Preserve the original R1 and each material's status as direct evidence, contextual evidence, or unverified.", "observed_result": "This belongs to the same RIBOFEM family as S10. The original bibliographic and access records are reused; effect values from the full results article are not filled in as values verified in this work.", "result_level": "Result details unverified within the same trial family", "materials": [ { "material_type": "PubMed bibliographic and abstract page for the results article", "public_status": "Currently unverified", "access_status": "External access not attempted in this work", "acquired": false, "actually_read": "Unread", "as_of": "2026-10-05", "qualification": "Result details unverified within the same trial family; access to external original materials was not attempted, and they were neither obtained nor read in this work.", "material_id": "S11-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/21525198/" } ], "links": [ { "label": "Official source", "url": "https://pubmed.ncbi.nlm.nih.gov/21525198/" } ] } ], "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly document the question, eligibility conditions and reasons for changes, and distinguish intervention variants.", "review_level": "Reuse of the preserved methods copy and historical principles from 1585. This is neither a new review of the full methods text nor certification through an official tool." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish and link studies and reports; do not omit studies solely because results are unreported.", "review_level": "Reuse of the preserved methods copy and historical principles from 1585. This is neither a new review of the full methods text nor certification through an official tool." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Fix the outcome and effect of interest when reviewing randomization, attrition, missing data, measurement and selective reporting.", "review_level": "Reuse of the preserved methods copy and historical principles from 1585. This is neither a new review of the full methods text nor certification through an official tool." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect values, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Reuse of the preserved methods copy and historical principles from 1585. This is neither a new review of the full methods text nor certification through an official tool." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence.", "review_level": "Reuse of the preserved methods copy and historical principles from 1585. This is neither a new review of the full methods text nor certification through an official tool." } ], "status_dictionary": { "Met": "The identity, original attribution, and scope of this condition were verified in the retained materials. This is separate from the sufficiency of the effect or clinical certification.", "Partly verified": "Some materials have been linked, but the actual analyses, procedures, or details remain to be verified.", "Unverified": "The clinical materials or values needed for this condition remain unverified within the scope of this reading. This is distinct from an effect of 0, AE 0, or incomplete table preparation.", "Not applicable": "An obligation to extend beyond the narrow principal question does not apply. This does not substitute for an unread status or a gap in the materials.", "Not applicable (alias)": "A gray display alias for Not applicable.", "Conflicting data": "An actual discrepancy in the original sources for the same item; distinct from numerical differences between different comparisons.", "Unread": "External original materials have not been directly read in the current work; this is separate from actually reading the retained summaries.", "Review incomplete": "An individual review for preparing the table is incomplete; this is separate from unverified materials." }, "study_overlap": { "state": "Do not newly count the 4 reports as 4 unique trials or independent replications. Preserve the original R1 and each material's status as direct evidence, contextual evidence, or unverified.", "unique_trial_count": null, "unique_participant_count": null, "reason": "Do not newly count the 4 reports as 4 unique trials or independent replications. Preserve the original R1 and each material's status as direct evidence, contextual evidence, or unverified." }, "history": [ { "date": "2026-11-01", "kind": "Public display and data separated", "view_version": "1.0", "change": "A public display and data were created from the existing 34 items. No new clinical search, change to verification status, or scoring was performed." } ], "language": "en", "translation_date": "2026-11-01" }