{
  "schema_version": "chamgap-public-evidence-check-1.0",
  "public_id": "v3108-main",
  "verdict_number": "3108",
  "title": "Folic acid, single added active ingredient by mouth × Hemoglobin increase in confirmed folate-deficient megaloblastic anemia",
  "view_version": "1.0",
  "view_created_date": "2026-11-05",
  "criteria_version": "NGM-v3108-ISOLATED-FOLATE-ANEMIA-HB-1.1",
  "criteria_date": "2026-10-05",
  "review_date": "2026-10-05",
  "legacy_evidence_date": "2026-09-15",
  "review_scope": {
    "materials_read": "Stored Korean and English manuscripts and case-specific criteria and application records",
    "clinical_papers_directly_read": false,
    "new_clinical_search": false,
    "limitation": "No external clinical abstracts, full texts, registrations or analysis plans were newly read. The stored records are distinguished from the links assembled for this public version, and the original verdict, numerical values and unverified information are preserved. No new search, calculation or reassessment was performed.",
    "date_meaning": "This is the date the stored materials were checked, not the date of an up-to-date clinical literature search."
  },
  "claim_context": {
    "population": "Nonpregnant, nonlactating adults; laboratory-confirmed isolated folate-deficient megaloblastic anemia; B12 deficiency excluded. Groups with special etiologies are kept separate.",
    "intervention": "Folic acid · The question is bounded to a single-ingredient oral preparation; the salt, dosage form and brand in an eligible trial remain unverified. · Oral",
    "dose": "Unverified — the dose and dosing frequency in an eligible comparison have not been verified.",
    "comparator": "Placebo, no treatment or usual care with no added folic acid, under the same background treatment. An actual eligible comparison remains unverified.",
    "endpoint": "Between-group difference in change in blood hemoglobin at a predefined follow-up time; an appropriately adjusted difference in final values is considered separately. Keep g/dL and g/L, and each time point, separate.",
    "duration": "Unverified — the treatment and follow-up durations in an eligible comparison have not been verified.",
    "excluded_extensions": [
      "MCV/reticulocytes/folate/clinical events as Hb substitutes",
      "Golding uncontrolled diet/B12 cointerventions",
      "oncology olaparib etiology and rescue",
      "alcohol/liver/bleeding and tropical-sprue causes",
      "MS multicomponent and pregnancy-prevention review"
    ]
  },
  "requirements": [
    {
      "item_id": "N01",
      "question_type": "Boundary of the distinct claim",
      "question": "Which population with deficiency, oral folic acid comparison and Hb outcome does this table address?",
      "needed": "The current original claim and specifications for laboratory confirmation, B12 exclusion, ingredient, route, background care and control, Hb and time point",
      "role": "Required",
      "role_reason": "Required to distinguish the historical combined claims about anemia, pregnancy and cardiovascular outcomes from the current single Hb question.",
      "application_exception": "Verifying the identity of the question does not verify the existence of an eligible comparison or the magnitude of the treatment effect.",
      "criterion": "Fix the question as a between-group Hb comparison at a predefined time in isolated folate-deficiency anemia, with oral folic acid as the sole addition versus no added folic acid under the same background care.",
      "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Future comparisons should first specify this population and the Hb effect of interest, and report other etiologies and endpoints as separate questions.",
      "current_reports": [],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The original claim is an increase in Hb in confirmed folate-deficient megaloblastic anemia. It was fixed as one comparison with oral folic acid as the sole addition under the same background care, and subclaims is an empty list.",
      "condition_status": "Met",
      "status_reason": "The original claim was linked to the inclusion and exclusion boundaries. This does not establish efficacy or constitute a new verdict.",
      "missingness": "The actual formulation, dose, duration and between-group results of an eligible comparison remain separately unverified.",
      "uncertainty": "The actual formulation, dose, duration and between-group results of an eligible comparison remain separately unverified.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "The current original claim and specifications for laboratory confirmation, B12 exclusion, ingredient, route, background care and control, Hb and time point"
    },
    {
      "item_id": "N02",
      "question_type": "Laboratory confirmation and B12 exclusion",
      "question": "How were isolated folate deficiency and megaloblastic anemia confirmed, and how was B12 deficiency excluded?",
      "needed": "The original diagnostic framework, serum/RBC folate, Hb/MCV, marrow, B12 and functional markers, and exclusion criteria",
      "role": "Required",
      "role_reason": "Required to avoid defining a confirmed isolated-deficiency population solely from low folate or an anemia heading.",
      "application_exception": "Unverified test details do not establish that no diagnosis was made. Inaccessible NICE cutoffs are not inserted as new criteria.",
      "criterion": "Cross-check confirmation of diagnosis and exclusion of mixed deficiency in the selected population against the actual locations of the test records.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Record the diagnostic and B12-exclusion procedures, and separate results for the confirmed isolated-deficiency population from those for other deficiency strata.",
      "current_reports": [
        "S01",
        "S08",
        "S09"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The question requires laboratory-confirmed isolated deficiency and exclusion of B12 deficiency, but the diagnostic cutoffs in an eligible comparison remain unverified. Golding's tests, marrow findings and B12 monitoring provide context; they are not themselves between-group results for this population.",
      "condition_status": "Partly verified",
      "status_reason": "The population specified by the question and some human test records are verified, but the confirmation criteria and separately identified population in an eligible comparison have not been verified.",
      "missingness": "Test values, thresholds and the population stratum with B12 deficiency excluded cannot be linked to a direct Hb comparison.",
      "uncertainty": "Test values, thresholds and the population stratum with B12 deficiency excluded cannot be linked to a direct Hb comparison.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "The original diagnostic framework, serum/RBC folate, Hb/MCV, marrow, B12 and functional markers, and exclusion criteria"
    },
    {
      "item_id": "N03",
      "question_type": "Other etiologies and special populations",
      "question": "Were groups with other etiologies, including pregnancy, mixed deficiencies, drugs, alcohol and malabsorption, distinguished?",
      "needed": "Information on diagnosis by etiology, coexisting deficiencies, pregnancy/lactation, age, liver and kidney status, drugs and malabsorption",
      "role": "Required",
      "role_reason": "Required to avoid combining material with different etiologies and treatment conditions solely because it shares the name anemia.",
      "application_exception": "Recovery in groups with other etiologies is preserved, and the reasons for exclusion are not used to claim no effect in those groups.",
      "criterion": "Specify the differences between the question about isolated deficiency in nonpregnant adults and the actual populations in related material.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Future studies should distinguish mixed deficiencies and special etiologies in advance and present direct comparisons separately for each population stratum.",
      "current_reports": [
        "S02",
        "S03",
        "S04",
        "S07",
        "S13"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Material on cancer/olaparib, alcohol/liver disease/bleeding, tropical sprue, pregnancy and combinations with B12 was not pooled with direct comparisons in adults with isolated deficiency. Pediatric cases and mixed B12/iron deficiency, renal disease, hemolysis, aplasia and inflammatory causes also remain outside that boundary.",
      "condition_status": "Met",
      "status_reason": "The population differences and reasons for exclusion stated in the original text were preserved. Extension to other populations has not been verified.",
      "missingness": "The direct Hb effect in this population stratum and effects in groups with other etiologies are not interchangeable.",
      "uncertainty": "The direct Hb effect in this population stratum and effects in groups with other etiologies are not interchangeable.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Information on diagnosis by etiology, coexisting deficiencies, pregnancy/lactation, age, liver and kidney status, drugs and malabsorption"
    },
    {
      "item_id": "N04",
      "question_type": "Chemical form and product identity",
      "question": "Were folic acid and the actual dosage form, manufacturer and product in an eligible comparison verified?",
      "needed": "Original records of chemical form, salt, sole active ingredient, dosage form, manufacturer, brand, batch and purity",
      "role": "Required",
      "role_reason": "Required to avoid treating folinic acid, 5-MTHF and combination products as the same intervention.",
      "application_exception": "The identity of the official 5 mg tablet belongs to that product's labeling; it is not assumed to be the same product used in an eligible trial.",
      "criterion": "Separate the folic acid specified in the question from the extent to which the product in an actual comparison has been verified.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Record the identifiable single-ingredient folic acid product and each group's product, batch, purity and other active ingredients.",
      "current_reports": [
        "S11"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The chemical form in the question is folic acid, distinguished from folinic acid and 5-MTHF. The salt, dosage form, brand, manufacturer, batch and purity in an eligible comparison remain unverified. The 5 mg oral tablet in S11 was retained only as product context.",
      "condition_status": "Partly verified",
      "status_reason": "The chemical form specified by the question and information about an official product are available, but the product in an eligible comparison has not been verified.",
      "missingness": "Official product labeling cannot be carried over as proof of identity with the actual trial product.",
      "uncertainty": "Official product labeling cannot be carried over as proof of identity with the actual trial product.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original records of chemical form, salt, sole active ingredient, dosage form, manufacturer, brand, batch and purity"
    },
    {
      "item_id": "N05",
      "question_type": "Route, dose and duration",
      "question": "Were the dose, dosing frequency, treatment duration and exposure of an eligible oral regimen verified?",
      "needed": "Original data on route, daily dose, dosing frequency, total exposure, treatment duration and concurrent supplementation for each eligible group",
      "role": "Required",
      "role_reason": "Required to avoid turning other routes, product labeling or doses from related trials into the regimen for the main question.",
      "application_exception": "The route in the question is oral, but the actual dose and duration of an eligible regimen remain unverified. No individual dose is specified.",
      "criterion": "Link only exposure from the actual comparison, and attribute labeled doses and doses used in groups with other etiologies separately.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Record actual use, adherence and concurrent supplementation for the sole oral addition, and directly compare justified dose/duration questions.",
      "current_reports": [
        "S02",
        "S11"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The dose, dosing frequency and treatment duration in an eligible comparison remain unverified. The 1 mg/day used in the olaparib population and the 5 mg/day for 4 months in the S11 label are not used as verified regimens for this question.",
      "condition_status": "Unverified",
      "status_reason": "The oral route is specified in the question, but the actual dose and duration in an eligible comparison could not be verified.",
      "missingness": "The optimal dose, duration, dosing schedule or equivalence of other routes cannot be determined.",
      "uncertainty": "The optimal dose, duration, dosing schedule or equivalence of other routes cannot be determined.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original data on route, daily dose, dosing frequency, total exposure, treatment duration and concurrent supplementation for each eligible group"
    },
    {
      "item_id": "N06",
      "question_type": "Same background care and actual control",
      "question": "Were background treatment apart from folic acid and a control without added folic acid actually compared?",
      "needed": "Original records of background treatment, concurrent supplementation, diet, transfusion, rescue treatment and the control without added folic acid for each group",
      "role": "Required",
      "role_reason": "Required to avoid attributing before-and-after recovery or asymmetric treatment changes to a between-group effect of folic acid alone.",
      "application_exception": "Shared treatment is not itself a reason for exclusion. Withholding treatment is not assumed to be acceptable, and ethically appropriate comparisons are distinguished.",
      "criterion": "Link the contrast for added folic acid under the same background care to the actual differences in background care.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M08 §8.1–8.2.3; internal application; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Define the ethically permissible comparison and effect of interest, and report background treatment, rescue treatment and changes by group.",
      "current_reports": [
        "S01",
        "S02"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The question specifies a control without added folic acid under the same background treatment, but an actual eligible comparison remains unverified. Golding had no concurrent control, and Shammo's controls also underwent olaparib dose reduction.",
      "condition_status": "Unverified",
      "status_reason": "The current related material alone cannot verify a between-group contrast under the same background care in the isolated-deficiency population.",
      "missingness": "The extent to which concurrent diet, drugs, transfusion and rescue treatment contributed to the outcome remains unverified.",
      "uncertainty": "The extent to which concurrent diet, drugs, transfusion and rescue treatment contributed to the outcome remains unverified.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original records of background treatment, concurrent supplementation, diet, transfusion, rescue treatment and the control without added folic acid for each group"
    },
    {
      "item_id": "N07",
      "question_type": "Hb measurements and other endpoints",
      "question": "Is the primary outcome the between-group change in Hb, distinguished from MCV, reticulocytes, folate and other measures?",
      "needed": "Hb definition, change/final values, units, direction of comparison, predefined follow-up time and a list of other endpoints",
      "role": "Required",
      "role_reason": "Required to avoid substituting other biochemical recovery for Hb comparison values.",
      "application_exception": "Trials of survival or transfusion events are not unconditionally required for a question about Hb itself. Such extensions require separate evidence.",
      "criterion": "Distinguish the between-group difference in change in blood Hb from an adjusted difference in final values, and keep g/dL, g/L and time points separate.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Define Hb measurement and analysis in advance, and report other markers, symptoms, transfusion and correction rates as separate outcomes.",
      "current_reports": [],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The primary outcome is the between-group difference in change in blood Hb at a predefined time; an appropriately adjusted difference in final values is separate. MCV, reticulocytes, folate concentrations, fatigue, transfusion and correction rates do not substitute for the primary outcome.",
      "condition_status": "Met",
      "status_reason": "The boundary between the selected endpoint and other endpoints was linked to the original text. An actual Hb effect estimate has not been verified.",
      "missingness": "The original Hb values, changes, adjustment status and units in a direct comparison remain unverified.",
      "uncertainty": "The original Hb values, changes, adjustment status and units in a direct comparison remain unverified.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Hb definition, change/final values, units, direction of comparison, predefined follow-up time and a list of other endpoints"
    },
    {
      "item_id": "N08",
      "question_type": "Predefined time point and follow-up coordinates",
      "question": "Can the fixed Hb follow-up time in an eligible comparison be distinguished from treatment and observation durations?",
      "needed": "Original registration/protocol records of the primary Hb time point, measurement schedule, treatment, discontinuation and follow-up duration",
      "role": "Required",
      "role_reason": "Required to avoid turning coordinates measured from the start of a study or a product's treatment duration into the fixed time point of a between-group comparison.",
      "application_exception": "Golding's days 586, 588 and 772 are study-day coordinates, not a prescribed general recovery timetable.",
      "criterion": "Distinguish the predefined follow-up time of an eligible comparison from time coordinates in related material.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Specify treatment exposure and the Hb follow-up schedule, and measure the effects of continuation and discontinuation as separate questions defined in advance.",
      "current_reports": [
        "S01"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The fixed Hb follow-up time and the treatment and follow-up durations in an eligible comparison remain unverified. The self-experiment's coordinates—diet resumed on day 586, a nadir near day 588 and return by day 772—are not repurposed as a treatment effect at a fixed time point.",
      "condition_status": "Unverified",
      "status_reason": "The time point in the main question was defined, but the predefined time point in an actual eligible comparison could not be verified.",
      "missingness": "No new treatment duration or mean recovery time is calculated from the observational coordinates.",
      "uncertainty": "No new treatment duration or mean recovery time is calculated from the observational coordinates.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original registration/protocol records of the primary Hb time point, measurement schedule, treatment, discontinuation and follow-up duration"
    },
    {
      "item_id": "N09",
      "question_type": "Hb testing and measurement conditions",
      "question": "Were Hb measurement and differences in transfusion, bleeding and testing that affect anemia verified?",
      "needed": "Records of the Hb assay, units, specimen/collection schedule, assessor blinding, transfusion, bleeding and changes by group in an eligible comparison",
      "role": "Required",
      "role_reason": "Required to distinguish measurement and clinical conditions contributing to Hb change from the contribution of folic acid.",
      "application_exception": "Failure to verify a measurement method in the current material is not expanded into a claim that it was unreported throughout the original paper.",
      "criterion": "Link Hb measurement conditions and the effects of other treatment or physiological changes to the actual comparison.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Standardize testing and specimen schedules, transfusion/bleeding and concurrent treatment, or report the actual differences and how they were handled analytically.",
      "current_reports": [
        "S03"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The Hb assay, measurement schedule, transfusion/bleeding by group and assessment procedures in the fixed comparison have not been verified. Recovery in a case involving alcohol, liver disease and bleeding is not used as a comparison with matched measurement conditions.",
      "condition_status": "Unverified",
      "status_reason": "No eligible material is available to link direct Hb values to measurement conditions.",
      "missingness": "Measurement limitations and other factors affecting Hb change in each group of the main comparison cannot be assessed quantitatively.",
      "uncertainty": "Measurement limitations and other factors affecting Hb change in each group of the main comparison cannot be assessed quantitatively.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Records of the Hb assay, units, specimen/collection schedule, assessor blinding, transfusion, bleeding and changes by group in an eligible comparison"
    },
    {
      "item_id": "N10",
      "question_type": "Eligible comparative design",
      "question": "Were the actual comparative design, allocation and baseline balance in the isolated-deficiency population verified?",
      "needed": "Original records of selection, design, allocation/concealment, baseline status, background care and control, and denominators in an eligible comparison",
      "role": "Required",
      "role_reason": "Required to distinguish the existence of human research from a direct comparative design for the selected question.",
      "application_exception": "Prospective observations are also preserved. Randomized placebo comparisons are not newly designated as the sole permissible evidence for replacement treatment.",
      "criterion": "Separate the currently known designs from the unverified status of a direct comparison in the isolated-deficiency population.",
      "basis": "M08 §8.1–8.2.3; internal application; M03 §3.2.1; detailed population criteria are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Specify an ethically permissible prospective comparison and the effect of interest, and record selection/allocation and baseline confounding.",
      "current_reports": [
        "S01",
        "S02"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Prospective human observation and a small comparison in a cancer population are verified, but an eligible between-group Hb design in adults with confirmed isolated deficiency and B12 deficiency excluded remains unverified. The original evidence_status records the existence of human data separately from the absence of an eligible comparison.",
      "condition_status": "Unverified",
      "status_reason": "Material with other designs or populations does not substitute for the direct-comparison gate.",
      "missingness": "Allocation/concealment, baseline balance and a causal comparison for the direct question cannot be verified.",
      "uncertainty": "Allocation/concealment, baseline balance and a causal comparison for the direct question cannot be verified.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original records of selection, design, allocation/concealment, baseline status, background care and control, and denominators in an eligible comparison"
    },
    {
      "item_id": "N11",
      "question_type": "Golding: design and denominator for 1 participant",
      "question": "Were the participant count and the number of analytical replicates in Golding's self-experiment distinguished?",
      "needed": "Original records of the self-experiment's design, participant/randomized/control counts and repeated tests",
      "role": "Required",
      "role_reason": "Required to avoid counting analytical replicates or specimens as new participants or independent comparisons.",
      "application_exception": "Recovery in 1 person is retained as information but is not converted into a between-group effect or population incidence.",
      "criterion": "Link the depletion-and-recovery trajectory of one person to the implications of having no concurrent control.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.1–8.2.3; internal application; M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "In prospective data, report participants, specimens and analytical replicates separately, and specify the limitations of the comparison.",
      "current_reports": [
        "S01"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Golding is a depletion-and-repletion self-experiment involving 1 participant. The randomized count is 0 and the eligible concurrent-control count is 0; analytical replicates are not participants. The recovery record is not a between-group Hb effect.",
      "condition_status": "Partly verified",
      "status_reason": "The design and participant count are verified, but they do not provide the comparison specified by the main question.",
      "missingness": "There is no concurrent control without added folic acid or formal between-group Hb estimate.",
      "uncertainty": "There is no concurrent control without added folic acid or formal between-group Hb estimate.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original records of the self-experiment's design, participant/randomized/control counts and repeated tests"
    },
    {
      "item_id": "N12",
      "question_type": "Golding: recovery and graphs",
      "question": "To what extent were Golding's Hb recovery timing and graph values read?",
      "needed": "The depletion-and-repletion timeline, reported Hb trajectory and extent of reading of the original graph",
      "role": "Required",
      "role_reason": "Required to preserve favorable recovery without converting an uncontrolled trajectory into an effect estimate.",
      "application_exception": "The graphs are not digitized, and the Hb value at the nadir is not reconstructed.",
      "criterion": "Retain the study-day coordinates and recovery narrative without turning them into a quantitative between-group comparison.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Observational studies should report Hb trajectories, times of changes and conditions that changed together, and distinguish causal effects from descriptive data.",
      "current_reports": [
        "S01"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Normal diet and folate supplementation resumed on study day 586; the Hb, red-cell count and hematocrit nadir was near day 588, and return to initial levels was reported by day 772. Numerical values were not reconstructed from graph heights.",
      "condition_status": "Partly verified",
      "status_reason": "The favorable recovery context and time coordinates are preserved, but they are not a controlled treatment effect or a general recovery duration.",
      "missingness": "The effect estimate cannot be reconstructed because no numerically read original Hb values, variance or control-group change are available.",
      "uncertainty": "The effect estimate cannot be reconstructed because no numerically read original Hb values, variance or control-group change are available.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "The depletion-and-repletion timeline, reported Hb trajectory and extent of reading of the original graph"
    },
    {
      "item_id": "N13",
      "question_type": "Golding: concurrent diet and B12",
      "question": "Were Golding's resumption of normal diet and concurrent B12 use distinguished from the contribution of folic acid?",
      "needed": "Original records of diet, folate, methylcobalamin, B12 tests and times of changes",
      "role": "Required",
      "role_reason": "Required to avoid attributing simultaneous dietary changes and cointerventions to the effect of folic acid alone.",
      "application_exception": "B12 monitoring and methylcobalamin administration are not treated as equivalent to diagnostic exclusion.",
      "criterion": "Link concurrent B12 at 1000 µg/day and resumption of diet to the context of the self-experiment.",
      "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Record concurrent nutrients, drugs, diet and the times of changes, and separate the incremental contribution of the ingredient of interest through an appropriate comparison.",
      "current_reports": [
        "S01"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Golding's participant maintained methylcobalamin 1000 µg/day and monitored B12 markers. Normal diet and folate supplementation resumed together, so the before-and-after recovery is not interpreted as an isolated between-group effect of folic acid.",
      "condition_status": "Partly verified",
      "status_reason": "Cointervention records are verified, but there is no control from which to estimate the independent contribution of folic acid.",
      "missingness": "The contributions of diet, B12 and folic acid cannot be disentangled.",
      "uncertainty": "The contributions of diet, B12 and folic acid cannot be disentangled.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original records of diet, folate, methylcobalamin, B12 tests and times of changes"
    },
    {
      "item_id": "N14",
      "question_type": "Olaparib: directness of the population",
      "question": "Is Shammo's cancer/olaparib population the same as a population with confirmed isolated folate-deficiency anemia?",
      "needed": "Original data on cancer/drugs, anemia/folate diagnosis, and the stratum with megaloblastic anemia and B12 deficiency excluded",
      "role": "Required",
      "role_reason": "Required to avoid transferring a comparison in cancer- or drug-induced anemia to isolated nutritional deficiency.",
      "application_exception": "The randomized component in the related material is not disregarded; the population mismatch and the unverified effect are retained separately.",
      "criterion": "Explain the differences between the olaparib-related population and the confirmed isolated-deficiency population, and the unverified status of the separately defined stratum.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Separate population strata with drug-induced causes from those with isolated deficiency, and report Hb comparisons by stratum.",
      "current_reports": [
        "S02"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Shammo is a prospective study of patients receiving olaparib for cancer. An eligible between-group Hb result for the stratum with confirmed megaloblastic anemia and B12 deficiency excluded could not be separately verified.",
      "condition_status": "Not met",
      "status_reason": "The currently verified population and outcomes do not meet the direct criteria of the question about adults with isolated deficiency.",
      "missingness": "Values from populations with other etiologies and strata that have not been separately verified cannot be used as the main effect.",
      "uncertainty": "Values from populations with other etiologies and strata that have not been separately verified cannot be used as the main effect.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original data on cancer/drugs, anemia/folate diagnosis, and the stratum with megaloblastic anemia and B12 deficiency excluded"
    },
    {
      "item_id": "N15",
      "question_type": "Olaparib: enrollment, allocation and completion",
      "question": "Were the 9 enrolled participants, the 2+2 allocated participants and the 12-month completion denominator distinguished?",
      "needed": "Original flow records for consent, enrollment, randomization, nonrandomization, completion and Hb analysis by group",
      "role": "Required",
      "role_reason": "Required to avoid using the entire cohort as the denominator for randomized Hb analyses.",
      "application_exception": "The total of 9 participants and the 5 completers are not the Hb analysis counts for each group. Analysis denominators absent from the original text are not filled in by arithmetic.",
      "criterion": "Attribute each count to its own stage: 10 consented, 9 enrolled, 4 allocated as 2+2, 5 nonrandomized, and 5 completing 12 months in the entire cohort.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.1–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Report the flow of the entire cohort separately from that of the allocated subgroup, and provide analysis denominators at each Hb time point.",
      "current_reports": [
        "S02"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Of 10 people who consented, 9 enrolled, and 4 were allocated as 2 to folic acid versus 2 to no supplementation. There were 5 nonrandomized participants, and the 5 who completed 12 months refer to the entire cohort. The fixed-time Hb analysis denominators by group remain unverified.",
      "condition_status": "Partly verified",
      "status_reason": "The overall flow is verified, but Hb analysis denominators by group and the fixed time point have not been verified.",
      "missingness": "Enrollment and completion counts cannot be reused as n for an eligible Hb result.",
      "uncertainty": "Enrollment and completion counts cannot be reused as n for an eligible Hb result.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original flow records for consent, enrollment, randomization, nonrandomization, completion and Hb analysis by group"
    },
    {
      "item_id": "N16",
      "question_type": "Olaparib: dose and rescue criteria",
      "question": "To which trial do Shammo's 1 mg/day dose and folate/Hb allocation and rescue criteria belong?",
      "needed": "The original trial dose, folate/Hb allocation criteria, rescue policy and actual use by group",
      "role": "Required",
      "role_reason": "Required to avoid extending an oncology trial's protocol into general diagnostic confirmation criteria or a treatment regimen.",
      "application_exception": "Rescue at Hb <10 g/dL is this trial's original protocol, not a threshold for withholding treatment from patients generally.",
      "criterion": "Attribute oral 1 mg/day, folate <7 ng/mL and Hb <12 g/dL, and rescue at Hb <10 g/dL to the oncology trial.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed; M19 §19.2.2–19.2.4 considerations for study design; detailed recording of confounding is internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Record the ethical rescue policy, actual timing of use and denominators, and specify its impact in the analysis of the effect of interest.",
      "current_reports": [
        "S02"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Shammo used oral folic acid at 1 mg/day. Allocation occurred at folate <7 ng/mL and Hb <12 g/dL, and the protocol specified starting rescue folate at Hb <10 g/dL regardless of allocation. This protocol is not used as universal criteria for confirming deficiency or megaloblastic anemia.",
      "condition_status": "Partly verified",
      "status_reason": "Exposure and protocol details for that oncology trial are preserved, but the regimen and analysis of rescue use for the main population remain unverified.",
      "missingness": "Actual rescue use and exposure by group are distinct from the diagnostic confirmation cutoffs for the main question.",
      "uncertainty": "Actual rescue use and exposure by group are distinct from the diagnostic confirmation cutoffs for the main question.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "The original trial dose, folate/Hb allocation criteria, rescue policy and actual use by group"
    },
    {
      "item_id": "N17",
      "question_type": "Olaparib: change in control",
      "question": "Were Shammo's change from the placebo plan and the actual control without supplementation distinguished?",
      "needed": "The original plan, reasons for changes, open-label/blinding status, actual control without supplementation and analysis documents",
      "role": "Required",
      "role_reason": "Required to avoid presenting the initially planned placebo as an actual blinded trial.",
      "application_exception": "The cost-related change is recorded, but the lack of an obtained protocol is not converted into a confirmed finding of selective reporting.",
      "criterion": "Link the abandonment of placebo and the comparison without supplementation to the actual design, and distinguish the amendment history.",
      "basis": "M08 §8.1–8.2.3; internal application; M08 Table 8.2.a, M04 §4.6.3; internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Transparently report the plan, reasons for changes, actual control, blinding and Hb analysis of interest.",
      "current_reports": [
        "S02",
        "S10"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Shammo's initial placebo plan changed to a control without supplementation because of cost. It is a small open-label randomized component within a prospective cohort and is not presented as a randomized double-blind placebo Hb trial.",
      "condition_status": "Partly verified",
      "status_reason": "The current retained wording verifies the difference between the planned and actual control, but the full protocol, SAP and amendment history remain unverified.",
      "missingness": "A complete cross-check of the planned control against actual allocation and analysis could not be performed.",
      "uncertainty": "A complete cross-check of the planned control against actual allocation and analysis could not be performed.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "The original plan, reasons for changes, open-label/blinding status, actual control without supplementation and analysis documents"
    },
    {
      "item_id": "N18",
      "question_type": "Olaparib: conflicting trial-phase wording",
      "question": "Were the phase IV and phase II/single-arm labels recorded in Shammo's original text preserved without arbitrarily harmonizing them?",
      "needed": "The relevant original pages, design wording, corrections or author explanations",
      "role": "Required",
      "role_reason": "Required to avoid inferring one actual phase from inconsistent design labels within the same report.",
      "application_exception": "The wording conflict is reported in the currently retained citation; the original full text was not independently rechecked in this review.",
      "criterion": "Preserve the discrepancy between p.1/3 phase IV and the p.2 phase II/single-arm template, together with their locations.",
      "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 §8.1–8.2.3; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Align design labels with the actual allocation component, and record an original explanation or correction as a separate event when available.",
      "current_reports": [
        "S02"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The retained citation records a discrepancy between the phase IV narrative on PDF p.1/3 and the phase II/single-arm template on p.2. The small randomized component actually linked in the record is retained, and the phase labels were not arbitrarily corrected.",
      "condition_status": "Conflicting information",
      "status_reason": "This is an explicit conflict in phase/design wording within the same report, not merely a difference between analyses.",
      "missingness": "The correct phase, the reason for the template change and any original correction currently remain unverified.",
      "uncertainty": "The correct phase, the reason for the template change and any original correction currently remain unverified.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "The relevant original pages, design wording, corrections or author explanations"
    },
    {
      "item_id": "N19",
      "question_type": "Olaparib: Hb and background medication",
      "question": "Were Shammo's interpretation of secondary Hb results and olaparib dose reduction kept from being converted into a between-group effect?",
      "needed": "Secondary Hb results, medication changes by group, formal Hb estimates/variance/time points and the original protocol",
      "role": "Required",
      "role_reason": "Required to avoid turning folate recovery, author narratives and asymmetric medication changes into a formal Hb effect.",
      "application_exception": "The authors' interpretation of Hb is preserved, but nonsignificance or unverified quantitative information is not used as equivalence or an effect of 0.",
      "criterion": "Attribute the primary frequency/timing of folate deficiency, secondary Hb and olaparib dose reduction in controls to their respective roles.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; M08 Table 8.2.a, M04 §4.6.3; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Predefine Hb as the outcome of interest, record background medication and rescue treatment, and report adjusted and sensitivity analyses for the comparison of interest.",
      "current_reports": [
        "S02"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Shammo's primary question concerns the frequency and timing of folate deficiency, and Hb is secondary. Olaparib dose reduction in controls is asymmetric, and a formal between-group Hb estimate for the fixed population stratum remains unverified. Recovery of deficient folate concentrations and the authors' interpretation are not converted into equivalence.",
      "condition_status": "Partly verified",
      "status_reason": "The endpoint hierarchy and changes in background care are preserved, but the direct Hb effect of interest could not be verified.",
      "missingness": "There are no Hb values with which to distinguish the contributions of analysis, adjustment and the control to the main question.",
      "uncertainty": "There are no Hb values with which to distinguish the contributions of analysis, adjustment and the control to the main question.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Secondary Hb results, medication changes by group, formal Hb estimates/variance/time points and the original protocol"
    },
    {
      "item_id": "N20",
      "question_type": "Alcohol and malabsorption material",
      "question": "How were Clarke's case and Sheehy's tropical-sprue material preserved?",
      "needed": "Case etiology, cointerventions/transfusion, administration/control, B12 exclusion, Hb values and the actual extent of access",
      "role": "Required",
      "role_reason": "Required to preserve related hematologic recovery without counting it as replication in isolated deficiency.",
      "application_exception": "Limited full-text access is not expanded into a claim of nonreporting in the original text or absence of research in this review.",
      "criterion": "Specify the differences between Clarke's 1-person case with mixed etiologies and Sheehy's malabsorption/dose-titration setting.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Report etiology, concurrent treatment, tests and denominators separately, and evaluate them through a comparison appropriate to that population's question.",
      "current_reports": [
        "S03",
        "S04"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Clarke is a 1-person case involving alcohol, liver disease and bleeding. Detailed transfusion counts, dose and a causal Hb effect remain unverified within the retained scope. Sheehy is a historical dose-titration study in tropical-sprue malabsorption; matching B12 exclusion and an Hb contrast for oral folic acid versus no added folic acid remain unverified.",
      "condition_status": "Not met",
      "status_reason": "The current populations and designs do not match the comparison of folic acid alone in adults with isolated deficiency. Recovery context and access limitations are retained.",
      "missingness": "Hematologic recovery from other etiologies cannot be transferred into an Hb estimate for the direct comparison.",
      "uncertainty": "Hematologic recovery from other etiologies cannot be transferred into an Hb estimate for the direct comparison.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Case etiology, cointerventions/transfusion, administration/control, B12 exclusion, Hb values and the actual extent of access"
    },
    {
      "item_id": "N21",
      "question_type": "Folate markers in people without anemia",
      "question": "Does Obeid's folate-marker study in nonpregnant women provide an Hb treatment result in confirmed anemia?",
      "needed": "Actual anemia diagnosis, baseline status, Hb outcomes, folate markers and the location of the selection information",
      "role": "Required",
      "role_reason": "Required to avoid inferring a treatment effect solely from the shared characteristic of being nonpregnant or from folate recovery.",
      "application_exception": "An exclusion recorded at index level is not converted into a quality review of the entire original full text or a finding of no effect.",
      "criterion": "Record the difference between biomarker supplementation material in people without anemia and the treatment question in confirmed megaloblastic anemia.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Separate baseline anemia and deficiency from outcomes, and provide a direct Hb comparison when the question concerns Hb treatment.",
      "current_reports": [
        "S06"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Obeid is an index-level lead identifying a folate-biomarker supplementation study in nonpregnant women. It was not used as a direct Hb effect of treatment for confirmed megaloblastic anemia, and the current n record is empty.",
      "condition_status": "Not met",
      "status_reason": "The currently verified population/endpoints differ from the Hb comparison in confirmed anemia specified by the main question.",
      "missingness": "Improved markers in people without anemia are not direct evidence of a between-group Hb change.",
      "uncertainty": "Improved markers in people without anemia are not direct evidence of a between-group Hb change.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Actual anemia diagnosis, baseline status, Hb outcomes, folate markers and the location of the selection information"
    },
    {
      "item_id": "N22",
      "question_type": "Combined B vitamins in MS",
      "question": "Can Nozari's combined B12+folic acid intervention in MS be separated into an effect of folic acid alone?",
      "needed": "The MS population, B12/folic acid interventions by group, Hb/anemia/quality-of-life outcomes and a contrast with a sole added ingredient",
      "role": "Required",
      "role_reason": "Required to avoid attributing combination results to folic acid alone when both the population and the added active ingredients differ.",
      "application_exception": "The favorable context of the combination data is preserved, and effects of individual ingredients are not arbitrarily disentangled.",
      "criterion": "Link MS and the addition of two active ingredients to their differences from the main population/intervention.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "If the question concerns each ingredient's contribution, design a direct contrast with matched background care and separate outcomes by disease.",
      "current_reports": [
        "S07"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Nozari is a comparison adding B12 and folic acid together in an MS population. It does not provide a between-group Hb result for folic acid as the sole addition in adults with isolated deficiency, and n remains unverified within the index-level access scope.",
      "condition_status": "Not met",
      "status_reason": "The population and intervention differ from the main question, and the contribution of folic acid alone cannot be isolated.",
      "missingness": "Results from a combination intervention and a different disease cannot be used as the selected ingredient's Hb effect.",
      "uncertainty": "Results from a combination intervention and a different disease cannot be used as the selected ingredient's Hb effect.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "The MS population, B12/folic acid interventions by group, Hb/anemia/quality-of-life outcomes and a contrast with a sole added ingredient"
    },
    {
      "item_id": "N23",
      "question_type": "Pregnancy review and reused citation",
      "question": "Were the pregnancy review and trials from historical record 121 kept from being counted as independent replications of replacement treatment in adults?",
      "needed": "The actual populations and prevention/treatment questions of the review/included trials, and links to original data",
      "role": "Required",
      "role_reason": "Required to avoid double-counting a historical combined-claim page and trials included in a review as replications of the new isolated-deficiency treatment question.",
      "application_exception": "The original file for historical record 121 was not read in this review; only the reused citation record in the current 3108 was read.",
      "criterion": "Distinguish a pregnancy-prevention review from Hb treatment in nonpregnant people with isolated deficiency, and do not infer the number of direct replications.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.1; detailed population criteria are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Link included trials to unique study families and their actual populations, interventions and outcomes, then separately review only material relevant to the question.",
      "current_reports": [
        "S13"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "S13 is the URL/citation of a pregnancy review inherited from the original 121. Pregnancy-prevention results and the historical combined-claim page were not counted as replications of deficiency treatment in nonpregnant people, and the original file was not reopened in this review.",
      "condition_status": "Not met",
      "status_reason": "The population and prevention/treatment boundary differ, so the criteria for direct treatment replication are not met.",
      "missingness": "Review counts, included-trial counts and participant counts are not summed for the main question.",
      "uncertainty": "Review counts, included-trial counts and participant counts are not summed for the main question.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "The actual populations and prevention/treatment questions of the review/included trials, and links to original data"
    },
    {
      "item_id": "N24",
      "question_type": "Between-group effect, variance and interval",
      "question": "Were the direct Hb difference in change, adjusted difference in final values, and SD/SE, CI and P verified?",
      "needed": "Original tables of Hb values/changes, units, n and SD/SE for each eligible group, the estimation model, CI and P",
      "role": "Required",
      "role_reason": "Required to avoid filling absent direct values with 0 or reconstructing them from graphs or other markers.",
      "application_exception": "Keep the variance type and CI unverified when they are unverified, and do not determine precision from sample size alone.",
      "criterion": "Separate between-group change from the adjusted difference in final values, and specify that variance, intervals and tests remain unverified.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Provide group-specific outcomes and variance, and the estimate and CI for the effect of interest; explain change/final-value analyses and adjustment variables.",
      "current_reports": [],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The fixed question's between-group Hb difference in change, adjusted difference in final values, variance, CI, P and analysis n by group remain unverified. The original calculation fields mean_changes, sd_changes, difference, interval and n are preserved as null.",
      "condition_status": "Unverified",
      "status_reason": "The inputs and estimates needed for a quantitative direct comparison are unavailable, so no interval could be verified for interpretation.",
      "missingness": "Empty values are distinct from an effect of 0, sufficient precision or nonsignificance. No new effect estimate or NNT is calculated.",
      "uncertainty": "Empty values are distinct from an effect of 0, sufficient precision or nonsignificance. No new effect estimate or NNT is calculated.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original tables of Hb values/changes, units, n and SD/SE for each eligible group, the estimation model, CI and P"
    },
    {
      "item_id": "N25",
      "question_type": "Analysis population and missing data",
      "question": "Were ITT/PP, completion/analysis denominators, missing data and Hb analysis in the main comparison verified?",
      "needed": "Flow, Hb measurement/analysis n, ITT/PP, reasons for and handling of missing data, and sensitivity analyses for each eligible group",
      "role": "Required",
      "role_reason": "Required to avoid turning enrollment, allocation or before-and-after measurement counts into actual Hb analysis denominators.",
      "application_exception": "Unverified analysis details are not converted into randomization failure, confirmed selective reporting or 0 missing observations.",
      "criterion": "Separate allocation, completion and analysis, and link the selected effect of interest to the unverified status of the actual analysis.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M08 Table 8.2.a, M04 §4.6.3; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Define the effect of interest and analysis population in advance, and report how missing Hb data, dropout and rescue treatment were handled by group, together with sensitivity analyses.",
      "current_reports": [
        "S02",
        "S10"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Eligible analysis and completion denominators by group, ITT/PP and missing-data handling for the main question remain unverified. Shammo's 5 completers at 12 months across the entire cohort were not used as Hb completion n for the two arms.",
      "condition_status": "Unverified",
      "status_reason": "Eligible Hb analysis information is unavailable, and the flow of a related cohort does not substitute for the main analysis.",
      "missingness": "Differences in the effect of interest arising from denominators, missing data and deviations cannot be assessed.",
      "uncertainty": "Differences in the effect of interest arising from denominators, missing data and deviations cannot be assessed.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Flow, Hb measurement/analysis n, ITT/PP, reasons for and handling of missing data, and sensitivity analyses for each eligible group"
    },
    {
      "item_id": "N26",
      "question_type": "Important difference and extension to clinical outcomes",
      "question": "Were the clinical importance of Hb and questions about symptoms, transfusion and survival distinguished?",
      "needed": "A justified criterion for an important Hb difference in the relevant population, and direct outcomes for symptoms, transfusion and quality of life/survival",
      "role": "Supplementary; required for claims about importance or extension to event outcomes",
      "role_reason": "Required to avoid extending the clinical scope of treatment benefit solely from a laboratory change.",
      "application_exception": "When the original question concerns Hb values, survival trials are not imposed as mandatory. No universal MCID, minimum participant count or duration is newly invented.",
      "criterion": "Distinguish the degree to which an Hb importance criterion is verified from the degree to which separate event evidence is verified.",
      "basis": "M15 §15.3.1–15.3.3; internal application; M03 §3.2.4; internally defined boundaries for extending the claim; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Justify an important Hb difference for the population and context, and measure patient-centered events as separate outcomes.",
      "current_reports": [],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "A clinically important Hb criterion for the main question remains unverified. Hb concentration is laboratory surrogate endpoint S and is not automatically extended to direct effects on fatigue, transfusion, correction rates or survival.",
      "condition_status": "Unverified",
      "status_reason": "The magnitude of clinical benefit cannot be determined because importance criteria and direct event outcomes have not been verified.",
      "missingness": "The gap in the Hb question is not expanded into absence of all patient benefit.",
      "uncertainty": "The gap in the Hb question is not expanded into absence of all patient benefit.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "A justified criterion for an important Hb difference in the relevant population, and direct outcomes for symptoms, transfusion and quality of life/survival"
    },
    {
      "item_id": "N27",
      "question_type": "Study families, funding and disclosures",
      "question": "To what extent were each report's family and funding/product/conflict-of-interest information verified?",
      "needed": "Unique-study/reused-citation relationships and original wording on research funding, product provision and author disclosures",
      "role": "Supplementary; required for a claim of independence",
      "role_reason": "Required to avoid inferring independent replication or verified funding solely from 13 reports and location references.",
      "application_exception": "Unverified conflicts of interest are not treated as independent support, and product documents are identified as manufacturer material.",
      "criterion": "Link evidence study_id, shared registration and material roles, and leave funding unverified where the original text is unavailable.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; Chamgap's own criteria for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Disclose family relationships, overlapping reports, funding and product roles, and verify independent direct comparisons through actual links.",
      "current_reports": [
        "S01",
        "S02",
        "S10",
        "S11",
        "S13"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "S02 and S10 are the paper and registration for NCT04024254. S11 is product labeling, and S13 is a reused citation of a historical review. Funding in evidence only refers to a separate evidence_appraisal.json, and citation only records the locations of COI/funding sections, so the actual disclosures are not described as verified in this review.",
      "condition_status": "Partly verified",
      "status_reason": "Verified families/roles were linked, but the detailed original values for funding, products and author disclosures are absent from the current stored summaries.",
      "missingness": "The unique direct-trial count, total participant count and independent support remain unverified. The historical separate appraisal file was not read.",
      "uncertainty": "The unique direct-trial count, total participant count and independent support remain unverified. The historical separate appraisal file was not read.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Unique-study/reused-citation relationships and original wording on research funding, product provision and author disclosures"
    },
    {
      "item_id": "N28",
      "question_type": "Registration, protocol and hierarchy",
      "question": "Were the registry shell and the original protocol/SAP, amendment history and current status distinguished?",
      "needed": "The original NCT04024254 registration/history, protocol, SAP, Hb hierarchy/time points and reasons for amendments",
      "role": "Required",
      "role_reason": "Required to avoid turning the existence of a registration number into proof of preregistration, endpoint agreement or current completion.",
      "application_exception": "Limited access to the original protocol does not establish nonregistration or selective reporting. It is also not a failed access attempt in this review.",
      "criterion": "Separate the retained identifier linkage from unverified registration timing, history and current status.",
      "basis": "M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Link the Hb outcome, time point and analysis of interest, and actual amendments, to public records and cross-check them against actual reporting.",
      "current_reports": [
        "S02",
        "S10"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "NCT04024254 is a registry-shell record linked to S02 Methods. Registration timing, amendments and current status were not independently certified in the historical review, and history/results/protocol contents are retained as not accessed.",
      "condition_status": "Partly verified",
      "status_reason": "The registration identity was linked, but the endpoints, time points, SAP and cross-check of the full history remain unverified.",
      "missingness": "The identifier and link alone do not establish preregistration or current recruitment/completion status.",
      "uncertainty": "The identifier and link alone do not establish preregistration or current recruitment/completion status.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "The original NCT04024254 registration/history, protocol, SAP, Hb hierarchy/time points and reasons for amendments"
    },
    {
      "item_id": "N29",
      "question_type": "B12 guideline version",
      "question": "Were BSH's replacement notice and the unverified NICE details distinguished?",
      "needed": "BSH version/update notices, the identity of NICE NG239 and the actual original diagnostic/treatment recommendations",
      "role": "Supplementary; required for diagnostic and safety applications",
      "role_reason": "Required to avoid presenting an old guideline as unchanged current guidance or filling in diagnostic criteria that have not been read.",
      "application_exception": "The original NICE recommendations were not read in this review, and the earlier failure to access the body text is retained as a historical record.",
      "criterion": "Separate the 2024 replacement notice for the 2014 document from the unverified scope of the original recommendations.",
      "basis": "M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M03 §3.2.1; detailed population criteria are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "When updating diagnostic/safety criteria, cross-check the actual original recommendations, version, applicable population and reasons for changes.",
      "current_reports": [
        "S08",
        "S09"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The retained record states that the BSH page identifies the document dated 2014-06-18 and, in its 2024-11-20 update, announces replacement of B12 guidance by NICE NG239 dated 2024-03-06. Exact NICE B12/MMA cutoffs and treatment instructions could not be extracted.",
      "condition_status": "Partly verified",
      "status_reason": "The replacement identity/version notice is preserved, but the original diagnostic details have not been verified.",
      "missingness": "The currency of the guideline as a whole, diagnostic cutoffs or individual treatment instructions are not newly established.",
      "uncertainty": "The currency of the guideline as a whole, diagnostic cutoffs or individual treatment instructions are not newly established.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "BSH version/update notices, the identity of NICE NG239 and the actual original diagnostic/treatment recommendations"
    },
    {
      "item_id": "N30",
      "question_type": "HTA of folate testing",
      "question": "Was the Swiss HTA's evidence on testing utility kept from being transferred into a claim of no effect of folic acid treatment?",
      "needed": "The HTA's question about the clinical utility of testing, original sections/pages and distinction from the treatment context",
      "role": "Required",
      "role_reason": "Required to avoid using a lack of evidence for the testing question to claim that replacement-treatment research or all human research is absent.",
      "application_exception": "Historical reading of some HTA narrative does not verify values in the original appendices or diagnostic cutoffs.",
      "criterion": "Separate the question of folate testing from the question of Hb treatment in isolated deficiency.",
      "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Evaluate patient outcomes and treatment comparisons for a testing strategy separately from direct replacement-treatment effects as distinct research questions.",
      "current_reports": [
        "S12"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The Swiss 2023 HTA evaluates the clinical utility of folate testing itself. Gaps in testing evidence were not repurposed as ineffectiveness of replacement treatment or a worldwide absence of treatment research. Only selected narrative sections were read at that time; numerical appendices and cutoffs could not be extracted.",
      "condition_status": "Met",
      "status_reason": "The difference between questions and the reading limitations in the current stored material were linked. This does not verify a treatment effect.",
      "missingness": "This HTA does not provide a direct between-group Hb result for the selected question.",
      "uncertainty": "This HTA does not provide a direct between-group Hb result for the selected question.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "The HTA's question about the clinical utility of testing, original sections/pages and distinction from the treatment context"
    },
    {
      "item_id": "N31",
      "question_type": "Official treatment context and labeled regimen",
      "question": "Were recognized replacement treatment and the dose on the S11 label distinguished from a direct comparative effect?",
      "needed": "S11 product identity, indication, labeled dose/duration and version, and the identity of an eligible trial",
      "role": "Required",
      "role_reason": "Required to avoid turning an authorized indication or 5 mg/4 months into a trial effect estimate or individual dosing instructions.",
      "application_exception": "An unverified direct effect is not interpreted as recognized treatment being unnecessary or as advice to delay treatment.",
      "criterion": "Retain recognized replacement treatment and product labeling, while separating them from verified between-group results and regimens.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Use labeling as treatment context, and report the actual comparison, exposure and Hb outcomes for the question of interest separately.",
      "current_reports": [
        "S11"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "S11 describes single-ingredient oral folic acid tablets and the indication of folate-deficient megaloblastic anemia. The adult regimen of 5 mg/day for 4 months belongs to that product's labeling; it is not the regimen of an eligible trial in this review, a placebo-controlled effect estimate or an individual instruction.",
      "condition_status": "Partly verified",
      "status_reason": "The official product's treatment context is a verified retained record, but the quantitative effect in the main comparison remains unverified.",
      "missingness": "Authorized labeling cannot be used as a between-group Hb estimate or as proof of identity with an eligible trial.",
      "uncertainty": "Authorized labeling cannot be used as a between-group Hb estimate or as proof of identity with an eligible trial.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "S11 product identity, indication, labeled dose/duration and version, and the identity of an eligible trial"
    },
    {
      "item_id": "N32",
      "question_type": "RE and treatment-ethics boundaries",
      "question": "Were the original nonapplication of RE, allowance for prospective observation and prohibition on withholding treatment retained unchanged?",
      "needed": "The original reasons for the RE decision, objective diagnosis/replacement mechanism, prospective observation and the extent of verification of the five gates at that time",
      "role": "Required",
      "role_reason": "Required to avoid turning the exception logic of the current original verdict into a new score, a mandatory placebo requirement or treatment delay.",
      "application_exception": "No new determination is made about whether RE is met or whether no treatment is ethically permissible. There is no assumption that withholding treatment is acceptable.",
      "criterion": "Preserve the allowance for prospective observation and the gates that were not established, and record the original RE_eligible=false unchanged.",
      "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M08 §8.1–8.2.3; internal application; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "First define an ethical comparison appropriate to this question and the effect of interest, then evaluate actual data; do not recommend a no-treatment experiment.",
      "current_reports": [
        "S01",
        "S02",
        "S11",
        "S12"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The original review acknowledged objective diagnosis, a direct replacement mechanism and prospective human observation. RE was not applied because proof of the historical absence of placebo trials and quantitative evidence of untreated mortality/irreversible harm were not obtained. The allowance for prospective observation is not changed into a requirement for a placebo RCT.",
      "condition_status": "Met",
      "status_reason": "The original RE logic and the boundaries for presenting treatment ethics were preserved accurately. RE was not newly adjudicated or established as met.",
      "missingness": "The missing gates were not established within the original verification scope; they are not a reason to delay recognized treatment.",
      "uncertainty": "The missing gates were not established within the original verification scope; they are not a reason to delay recognized treatment.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "The original reasons for the RE decision, objective diagnosis/replacement mechanism, prospective observation and the extent of verification of the five gates at that time"
    },
    {
      "item_id": "N33",
      "question_type": "B12 masking and neurological risk",
      "question": "Was improvement in Hb distinguished from resolution of neurological problems due to B12 deficiency?",
      "needed": "S11 contraindications and precautions for B12 deficiency/undiagnosed anemia, and actual neurological-harm definitions and exposure/denominator data",
      "role": "Supplementary; required for safety boundaries",
      "role_reason": "Required to avoid implying that hematologic improvement means resolution of B12 deficiency or neurological safety.",
      "application_exception": "The official warning is product context and does not determine incidence or individual risk in the isolated-deficiency population.",
      "criterion": "Record warnings about masking B12 findings and delayed recognition separately from Hb recovery and unverified frequency.",
      "basis": "M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed differentiation is internally designed; M19 §19.2.2–19.2.4 considerations for study design; detailed recording of confounding is internally designed; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Record B12 exclusion and neurological observations, and separately collect actual harm definitions, timing, exposure and denominators.",
      "current_reports": [
        "S11"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "S11 warns against treating B12 deficiency/undiagnosed anemia with folic acid alone, because folic acid can improve the hematologic findings of B12 deficiency and delay recognition of neurological damage. Hb recovery is not evidence that the B12 problem has been resolved.",
      "condition_status": "Partly verified",
      "status_reason": "The label warning is preserved, but the frequency of neurological harm in the selected population and at the selected dose remains unverified.",
      "missingness": "Incidence, latency, discontinuation/recovery, exposure amount and denominators could not be verified.",
      "uncertainty": "Incidence, latency, discontinuation/recovery, exposure amount and denominators could not be verified.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "S11 contraindications and precautions for B12 deficiency/undiagnosed anemia, and actual neurological-harm definitions and exposure/denominator data"
    },
    {
      "item_id": "N34",
      "question_type": "Adverse reactions, drugs and denominators",
      "question": "Were gastrointestinal and allergic reactions and interactions distinguished from actual event denominators in the eligible population?",
      "needed": "Original data on AE/SAE, discontinuation, exposure/duration, collection methods, people with events/event counts and concomitant drugs for each eligible group",
      "role": "Supplementary; required for frequency/safety claims",
      "role_reason": "Required to avoid turning a product's reaction list into comparative event rates or absence of risk in the main population.",
      "application_exception": "The statuses Not read and Unverified are not converted into 0 people with adverse reactions/SAE/discontinuation.",
      "criterion": "Distinguish S11's gastrointestinal/allergic and antiepileptic/methotrexate context from the gap in direct event rates.",
      "basis": "M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed differentiation is internally designed; M19 §19.2.2–19.2.4, M03 §3.2.3; internal application; M19 §19.2.2–19.2.4 considerations for study design; detailed recording of confounding is internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Report harm definitions, systematic collection, people/event counts, exposure time and denominators by group, and analyze drug interactions in their relevant context.",
      "current_reports": [
        "S05",
        "S11"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The context of gastrointestinal and allergic adverse reactions and interactions with antiepileptics and methotrexate in the product label was preserved. This is not AE/SAE, discontinuation-count, denominator or incidence data for the main isolated-deficiency population.",
      "condition_status": "Partly verified",
      "status_reason": "Warning/reaction context is available, but comparative frequencies and the extent of data collection for the same population and exposure remain unverified.",
      "missingness": "Event rates, safety equivalence and absence of serious harm cannot be verified.",
      "uncertainty": "Event rates, safety equivalence and absence of serious harm cannot be verified.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original data on AE/SAE, discontinuation, exposure/duration, collection methods, people with events/event counts and concomitant drugs for each eligible group"
    },
    {
      "item_id": "N35",
      "question_type": "Long-term use and special populations",
      "question": "Can safety/efficacy be extended to high doses, long-term use, liver or kidney disease, cancer, malabsorption, pregnancy/lactation and children?",
      "needed": "Actual exposure/effect by population, dose and duration, rare/long-term harms, and drug/underlying-disease data",
      "role": "Supplementary; required for extension claims",
      "role_reason": "Required to avoid extending related product context or brief recovery to safety/efficacy in all populations.",
      "application_exception": "Studies in every special population are not imposed as mandatory for the original Hb question, and individual dosing instructions are not provided.",
      "criterion": "Record the question about nonpregnant adults with isolated deficiency separately from the unverified scope for each special population.",
      "basis": "M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied; M03 §3.2.1; detailed population criteria are internally designed",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "For each extension question, separately collect appropriate design, exposure, long-term follow-up and outcomes in vulnerable populations.",
      "current_reports": [
        "S11"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "Applicability differs for long-term high doses, liver or kidney disease, malabsorption, a history of cancer, pregnancy/lactation and children. Their efficacy, incidence or safety is not established from the current main question or product labeling.",
      "condition_status": "Unverified",
      "status_reason": "Direct material for each extension has not currently been verified, and the populations also differ from the original question.",
      "missingness": "Unverified does not mean no risk or no effect, and it does not certify extended applicability.",
      "uncertainty": "Unverified does not mean no risk or no effect, and it does not certify extended applicability.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Actual exposure/effect by population, dose and duration, rare/long-term harms, and drug/underlying-disease data"
    },
    {
      "item_id": "N36",
      "question_type": "Current and historical reading",
      "question": "Was historical access for the 13 bibliographic records distinguished from reading local summaries in this review?",
      "needed": "Material type, URL, historical access_level/flag, dates and original locations for each report, and exact current stored-summary anchors",
      "role": "Required",
      "role_reason": "Required to avoid upgrading original full-text access flags and links into full-text reading in this review.",
      "application_exception": "Access to all external material is currently unattempted, and none of it has been read in this review; historical failures are not presented as failures in this review.",
      "criterion": "Separate actual reading, acquisition and access status by material type into current and historical records, and leave records without access dates empty.",
      "basis": "M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "During any authorized subsequent material check, record original locations, material type, dates, acquisition/reading and access failures separately.",
      "current_reports": [
        "S01",
        "S02",
        "S03",
        "S04",
        "S05",
        "S06",
        "S07",
        "S08",
        "S09",
        "S10",
        "S11",
        "S12",
        "S13"
      ],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "In this review, the Korean text/structure of the current stored summaries and 13 bibliographic records were read. Historical levels such as Golding HTML, parsed Shammo text and official labeling/HTA are retained reports; no clinical full text was read in this review. Report-specific access dates are absent and left empty, while the original review date is separately recorded as 2026-09-15.",
      "condition_status": "Met",
      "status_reason": "Actual summary reading was separated from current nonreading and historical access by material type. This does not mean full-text verification was completed.",
      "missingness": "The original clinical files, registrations and full official web texts have not currently been obtained, and the historical ZIP/separate logs were not read either.",
      "uncertainty": "The original clinical files, registrations and full official web texts have not currently been obtained, and the historical ZIP/separate logs were not read either.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Material type, URL, historical access_level/flag, dates and original locations for each report, and exact current stored-summary anchors"
    },
    {
      "item_id": "N37",
      "question_type": "Original-verdict and publication boundaries",
      "question": "Were the original ?/empty values, axes, safety and publication records distinguished from the new criteria statuses?",
      "needed": "Original grade/score/axes, calculation, evidence_status, publication/server metadata and the scope of the new table",
      "role": "Required",
      "role_reason": "Required to avoid carrying over the original score or internal deployment metadata as new efficacy, safety or completed public website publication.",
      "application_exception": "The original first_published_at is the content baseline date; server_deployed and server_write=false are retained records.",
      "criterion": "Preserve the original verdict values byte for byte, and separate them from criteria statuses and the fact that this public version has not been deployed.",
      "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Separate material/criteria updates from the original clinical verdict and events of public release, preserving the original text before and after changes.",
      "current_reports": [],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The original grade is ?, score is null, safety is Caution, and the five axes beyond B/S are null. The existence of human research is distinguished from unverified directly eligible results. The original server_deployed=true, server_write=false and 2026-09-15 publication metadata are historical records; the new table has not been deployed.",
      "condition_status": "Met",
      "status_reason": "The original verdict and scope metadata were preserved, and no new score or efficacy judgment was assigned to criteria statuses.",
      "missingness": "Criteria checks, technical checks passed and original server flags are not independent clinical certification or evidence of current incorporation into the website.",
      "uncertainty": "Criteria checks, technical checks passed and original server flags are not independent clinical certification or evidence of current incorporation into the website.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "Original grade/score/axes, calculation, evidence_status, publication/server metadata and the scope of the new table"
    },
    {
      "item_id": "N38",
      "question_type": "Search limitations and links to updates",
      "question": "What would actually update the gaps within the retained search scope of 2026-09-15?",
      "needed": "New direct Hb results, actual original texts/protocols, corrections/retractions, and evidence of numerical, classification, diagnostic and safety changes",
      "role": "Required",
      "role_reason": "Required to avoid turning a limited current value into an up-to-date exhaustive search or a claim of permanent absence.",
      "application_exception": "This is not a new search, correction/retraction lookup, calculation or reassessment. Revision of criteria and addition of evidence are separate events.",
      "criterion": "Record the original cutoff date, incompleteness, unchanged ID/URL, reasons for changes and re-review of linked rows.",
      "basis": "M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application",
      "condition_origin": "Case-specific necessary criteria were designed internally and reviewed by the model with the current material already known. This was not blinded review, clinical preregistration or official methodological certification.",
      "proposed_research": "Subsequent updates should establish material identity, dates, original locations and reading scope, and cross-check the question of interest together with the original results and gaps.",
      "current_reports": [],
      "existence": "The statements/values in the currently linked stored summaries are present. This does not verify their current external availability or establish efficacy.",
      "acquired_read": "Summary read: the exact locations in the current locally stored summaries were read. Access to the external material was not attempted, and that material was not read in this review.",
      "observation": "The original cutoff date is 2026-09-15, and the search was limited, including selected full texts, abstracts and inaccessible material. The retained policy is to append to the history under the same ID/URL when new matching Hb results, original texts/protocols, corrections/retractions, numerical/classification errors or B12 diagnostic/safety changes are actually verified.",
      "condition_status": "Met",
      "status_reason": "The scope of the original gaps was distinguished from update events. This does not mean new material has been verified or the search is complete.",
      "missingness": "The referenced historical search/numerical/appraisal logs and ZIP were not opened in this review, and the latest external status remains unverified.",
      "uncertainty": "The referenced historical search/numerical/appraisal logs and ZIP were not opened in this review, and the latest external status remains unverified.",
      "review_date": "2026-10-05",
      "reading_status": "Original source not read · Stored summary read",
      "additional_material": "New direct Hb results, actual original texts/protocols, corrections/retractions, and evidence of numerical, classification, diagnostic and safety changes"
    }
  ],
  "reports": [
    {
      "report_id": "S01",
      "title": "Golding 2014: Severe experimental folate deficiency in a human subject",
      "url": "https://link.springer.com/article/10.1186/2193-1801-3-442",
      "report_type": "Before-and-after observation of depletion and repletion in 1 person",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "FAM-GOLDING-2014",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "This is a self-experiment with 1 participant. There is no concurrent control without added folic acid, and the context includes resumption of normal diet, folate and methylcobalamin 1000 µg/day. Resumption on study day 586, the nadir near day 588 and recovery by day 772 describe a trajectory; Hb values or between-group effects were not reconstructed from graphs.",
      "result_level": "Before-and-after observation of depletion and repletion in 1 person; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full text of the paper",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S01-M1",
          "url": "https://link.springer.com/article/10.1186/2193-1801-3-442",
          "parent_url": "https://link.springer.com/article/10.1186/2193-1801-3-442"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://link.springer.com/article/10.1186/2193-1801-3-442"
        }
      ]
    },
    {
      "report_id": "S02",
      "title": "Shammo et al. 2025: A prospective study of serum folate levels in patients with solid tumors treated with olaparib",
      "url": "https://academic.oup.com/oncolo/article-pdf/30/10/oyaf321/64417912/oyaf321.pdf",
      "report_type": "Small comparison within a prospective cancer/olaparib cohort",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "FAM-OLAPARIB-NCT04024254",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "Of 10 people who consented and 9 who enrolled, 4 were allocated as 2 to folic acid versus 2 to no supplementation; the 5 who completed 12 months in the entire cohort are not the Hb analysis denominators by group. Oral 1 mg/day, allocation/rescue criteria, abandonment of placebo because of cost and dose reduction of the drug in controls were preserved. Hb is secondary, and a formal Hb effect in the stratum with confirmed isolated deficiency/B12 exclusion remains unverified. The phase IV versus phase II/single-arm wording conflict was also retained.",
      "result_level": "Small comparison within a prospective cancer/olaparib cohort; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full text of the paper",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S02-M1",
          "url": "https://academic.oup.com/oncolo/article-pdf/30/10/oyaf321/64417912/oyaf321.pdf",
          "parent_url": "https://academic.oup.com/oncolo/article-pdf/30/10/oyaf321/64417912/oyaf321.pdf"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://academic.oup.com/oncolo/article-pdf/30/10/oyaf321/64417912/oyaf321.pdf"
        }
      ]
    },
    {
      "report_id": "S03",
      "title": "Clarke and Weston-Smith 2010: Severe folate-deficiency pancytopenia",
      "url": "https://pubmed.ncbi.nlm.nih.gov/22791479/",
      "report_type": "Case involving alcohol, liver disease and bleeding in 1 person",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "FAM-CLARKE-2010",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "This provides context on hematologic recovery in a case involving 1 person. Alcohol, liver disease and bleeding coexist, and detailed transfusion counts, folic acid dose and a causal Hb effect remain unverified within the retained access scope. It is not a controlled mean Hb effect in the isolated-deficiency population.",
      "result_level": "Case involving alcohol, liver disease and bleeding in 1 person; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full bibliographic/abstract web document",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S03-M1",
          "url": "https://pubmed.ncbi.nlm.nih.gov/22791479/",
          "parent_url": "https://pubmed.ncbi.nlm.nih.gov/22791479/"
        },
        {
          "material_type": "Full text of the paper",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. The current record has no direct URL for the relevant full text/protocol. A bibliographic URL is not converted into a full-text download link. This does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S03-M2",
          "url": null,
          "parent_url": "https://pubmed.ncbi.nlm.nih.gov/22791479/"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://pubmed.ncbi.nlm.nih.gov/22791479/"
        }
      ]
    },
    {
      "report_id": "S04",
      "title": "Sheehy et al. 1961: The effect of minute and titrated amounts of folic acid on the megaloblastic anemia of tropical sprue",
      "url": "https://pubmed.ncbi.nlm.nih.gov/13911562/",
      "report_type": "Historical dose-titration material in tropical sprue",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "FAM-SHEEHY-1961",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "This is a historical dose-titration study in a malabsorption population. The current n is a string representing an empty object, and B12 exclusion, a comparison of oral folic acid against a control without added folic acid, and Hb values for the fixed population remain unverified. Historical failure to access the publisher's original full text is not presented as a failure in this review.",
      "result_level": "Historical dose-titration material in tropical sprue; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full bibliographic/abstract web document",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S04-M1",
          "url": "https://pubmed.ncbi.nlm.nih.gov/13911562/",
          "parent_url": "https://pubmed.ncbi.nlm.nih.gov/13911562/"
        },
        {
          "material_type": "Full text of the paper",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. The current record has no direct URL for the relevant full text/protocol. A bibliographic URL is not converted into a full-text download link. This does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S04-M2",
          "url": null,
          "parent_url": "https://pubmed.ncbi.nlm.nih.gov/13911562/"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://pubmed.ncbi.nlm.nih.gov/13911562/"
        }
      ]
    },
    {
      "report_id": "S05",
      "title": "NIH ODS Folate health-professional fact sheet",
      "url": "https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/",
      "report_type": "Limited historical access to official nutrition and safety context",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "OFFICIAL-ODS-FOLATE",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "ODS is a lead for safety and medication context. The record preserves initial access to body text followed by repeated access failures and states that safety interpretations requiring exact wording were corroborated by S11. No new numerical UL was invented from unverified sections, and this is not Hb treatment-effect data.",
      "result_level": "Limited historical access to official nutrition and safety context; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full official web document",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S05-M1",
          "url": "https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/",
          "parent_url": "https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/"
        }
      ]
    },
    {
      "report_id": "S06",
      "title": "Obeid et al. 2017: Folate supplementation in nonpregnant women",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6060806/",
      "report_type": "Index-level lead on folate-biomarker supplementation in people without anemia",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "FAM-OBEID-2017",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "The record states that folate-biomarker supplementation material in nonpregnant women was reviewed at index level. This differs from Hb treatment of confirmed megaloblastic anemia, and current n and direct Hb values remain unverified. It is not upgraded into a review of the quality/effects of the entire original full text.",
      "result_level": "Index-level lead on folate-biomarker supplementation in people without anemia; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full text of the paper",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S06-M1",
          "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6060806/",
          "parent_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6060806/"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6060806/"
        }
      ]
    },
    {
      "report_id": "S07",
      "title": "Nozari et al. 2019: Folic acid and vitamin B12 supplementation in multiple sclerosis",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6355946/",
      "report_type": "Index-level lead on combined B12+folic acid in MS",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "FAM-NOZARI-2019",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "This is a comparison adding B12+folic acid together in an MS population. The Hb effect of folic acid as the sole addition in isolated folate deficiency was not separated, and current n remains unverified. Material with a different population and ingredients is not used as direct replication.",
      "result_level": "Index-level lead on combined B12+folic acid in MS; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full text of the paper",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S07-M1",
          "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6355946/",
          "parent_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6355946/"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6355946/"
        }
      ]
    },
    {
      "report_id": "S08",
      "title": "British Society for Haematology: Diagnosis of B12 and Folate Deficiency",
      "url": "https://b-s-h.org.uk/guidelines/guidelines/diagnosis-of-b12-and-folate-deficiency",
      "report_type": "Notice of a historical guideline's version and replacement status",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "OFFICIAL-BSH-STATUS",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "The retained record states that the page for the 2014 BSH document and its 2024 update announce replacement of B12-related guidance by NICE NG239. The old document is not presented as unchanged current guidance. The full original guideline and exact diagnostic criteria were not read in this review.",
      "result_level": "Notice of a historical guideline's version and replacement status; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full official web document",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S08-M1",
          "url": "https://b-s-h.org.uk/guidelines/guidelines/diagnosis-of-b12-and-folate-deficiency",
          "parent_url": "https://b-s-h.org.uk/guidelines/guidelines/diagnosis-of-b12-and-folate-deficiency"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://b-s-h.org.uk/guidelines/guidelines/diagnosis-of-b12-and-folate-deficiency"
        }
      ]
    },
    {
      "report_id": "S09",
      "title": "NICE NG239: Vitamin B12 deficiency in over 16s—diagnosis and management",
      "url": "https://www.nice.org.uk/guidance/ng239/chapter/Recommendations",
      "report_type": "NICE recommendations URL linked by BSH; body text not obtained at that time",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "OFFICIAL-NICE-NG239",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "The identity and official link of NG239 are linked to BSH's replacement notice. Historical direct access to the recommendations' body text failed, and exact B12/MMA cutoffs or treatment instructions could not be extracted. This is not used as evidence of current access, reading of the body text or verification of the latest content.",
      "result_level": "NICE recommendations URL linked by BSH; body text not obtained at that time; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full official web document",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S09-M1",
          "url": "https://www.nice.org.uk/guidance/ng239/chapter/Recommendations",
          "parent_url": "https://www.nice.org.uk/guidance/ng239/chapter/Recommendations"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://www.nice.org.uk/guidance/ng239/chapter/Recommendations"
        }
      ]
    },
    {
      "report_id": "S10",
      "title": "ClinicalTrials.gov NCT04024254",
      "url": "https://clinicaltrials.gov/study/NCT04024254",
      "report_type": "Registry shell for the same olaparib study",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "FAM-OLAPARIB-NCT04024254",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "The identifier NCT04024254 is linked to S02 Methods. Registration timing, amendments and current status were not independently certified in the historical review, and history, results and protocol contents were not obtained. The paper and registration for the same study are not counted as two independent trials.",
      "result_level": "Registry shell for the same olaparib study; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full registry web document",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S10-M1",
          "url": "https://clinicaltrials.gov/study/NCT04024254",
          "parent_url": "https://clinicaltrials.gov/study/NCT04024254"
        },
        {
          "material_type": "Full study protocol and analysis plan",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. The current record has no direct URL for the relevant full text/protocol. A bibliographic URL is not converted into a full-text download link. This does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S10-M2",
          "url": null,
          "parent_url": "https://clinicaltrials.gov/study/NCT04024254"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://clinicaltrials.gov/study/NCT04024254"
        }
      ]
    },
    {
      "report_id": "S11",
      "title": "Flamingo Pharma folic acid 5 mg tablet SmPC, text revised 20 May 2026",
      "url": "https://www.medicines.org.uk/emc/product/14604/smpc",
      "report_type": "Official labeling for a single-ingredient folic acid product",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "OFFICIAL-FOLIC-ACID-LABEL",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "The indication of folate-deficient megaloblastic anemia and the adult label regimen of 5 mg/day for 4 months for a single-ingredient oral folic acid 5 mg tablet were preserved. These belong to that product's labeling, not an eligible trial regimen, Hb effect or individual instruction. The B12/undiagnosed-anemia warning, gastrointestinal/allergic, medication and pregnancy contexts, and the 2026 version were linked separately.",
      "result_level": "Official labeling for a single-ingredient folic acid product; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full official web document",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S11-M1",
          "url": "https://www.medicines.org.uk/emc/product/14604/smpc",
          "parent_url": "https://www.medicines.org.uk/emc/product/14604/smpc"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://www.medicines.org.uk/emc/product/14604/smpc"
        }
      ]
    },
    {
      "report_id": "S12",
      "title": "Swiss Federal Office of Public Health 2023 HTA: Folate Testing",
      "url": "https://www.bag.admin.ch/dam/de/sd-web/QuwyTqPLhnpP/h0041folt-hta-report.pdf",
      "report_type": "Official HTA of the clinical utility of folate testing",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "OFFICIAL-SWISS-FOLATE-HTA",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "The 2023 Swiss HTA concerns the clinical utility of folate testing itself. Historical reading of selected narrative sections and a screenshot failure are preserved; numerical appendices/diagnostic cutoffs were not extracted. Gaps in testing evidence are not converted into ineffectiveness of replacement treatment or absence of treatment research.",
      "result_level": "Official HTA of the clinical utility of folate testing; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full official HTA report",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S12-M1",
          "url": "https://www.bag.admin.ch/dam/de/sd-web/QuwyTqPLhnpP/h0041folt-hta-report.pdf",
          "parent_url": "https://www.bag.admin.ch/dam/de/sd-web/QuwyTqPLhnpP/h0041folt-hta-report.pdf"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://www.bag.admin.ch/dam/de/sd-web/QuwyTqPLhnpP/h0041folt-hta-report.pdf"
        }
      ]
    },
    {
      "report_id": "S13",
      "title": "Existing record 121: broad anemia, pregnancy and cardiovascular folic acid claims",
      "url": "https://pubmed.ncbi.nlm.nih.gov/23543547/",
      "report_type": "Pregnancy-review citation inherited from historical record 121",
      "existence": "This is a reference from stored bibliographic information and existing records; the current external response has not been checked.",
      "acquired_read": "The relevant summary and bibliographic record in the stored manuscript were checked. The linked external source material was not read in this review.",
      "study_family": "FAM-LASSI-PREGNANCY-REVIEW",
      "independent_replication": "Only currently retained study/material relationships were linked. The same paper, registration, historical review and official documents are not counted as independent direct trials.",
      "observed_result": "Only the reused citation record from historical 121 in the current 3108 was read. It is a lead to the review URL and identity for PMID 23543547; pregnancy prevention and the historical combined-claim page are not counted as replications of isolated-deficiency treatment in nonpregnant people. The original 121, review and included trials were not reopened in this review.",
      "result_level": "Pregnancy-review citation inherited from historical record 121; within the retained scope of the original review dated 2026-09-15, not a reading of clinical source material in this review.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full bibliographic/abstract web document",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. This is the retained entry URL for the material, not successful access, acquisition or reading in this review. It does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S13-M1",
          "url": "https://pubmed.ncbi.nlm.nih.gov/23543547/",
          "parent_url": "https://pubmed.ncbi.nlm.nih.gov/23543547/"
        },
        {
          "material_type": "Full text of the review paper",
          "public_status": "Currently unverified (no external lookup)",
          "access_status": "Access not attempted",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-10-05",
          "qualification": "Local summaries/historical access flags are distinguished from the fact that external material has not been read in the current review. The current record has no direct URL for the relevant full text/protocol. A bibliographic URL is not converted into a full-text download link. This does not mean that external source material was accessed, obtained or read in this review. Stored manuscripts and external source material are distinguished.",
          "material_id": "S13-M2",
          "url": null,
          "parent_url": "https://pubmed.ncbi.nlm.nih.gov/23543547/"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://pubmed.ncbi.nlm.nih.gov/23543547/"
        }
      ]
    }
  ],
  "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 record the question, eligibility criteria and reasons for changes, and distinguish variations in the intervention.",
      "review_level": "The copies, SHA values and methodological principles retained from 1585 were reused as historical material. This is not new reading of full methodological texts, application of an official tool or clinical certification in this review."
    },
    {
      "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, and do not omit a study solely because its outcomes are not reported.",
      "review_level": "The copies, SHA values and methodological principles retained from 1585 were reused as historical material. This is not new reading of full methodological texts, application of an official tool or clinical certification in this review."
    },
    {
      "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": "Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting.",
      "review_level": "The copies, SHA values and methodological principles retained from 1585 were reused as historical material. This is not new reading of full methodological texts, application of an official tool or clinical certification in this review."
    },
    {
      "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 estimates, intervals, importance and applicability. Sample size alone does not determine precision.",
      "review_level": "The copies, SHA values and methodological principles retained from 1585 were reused as historical material. This is not new reading of full methodological texts, application of an official tool or clinical certification in this review."
    },
    {
      "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": "Questions about harms may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence.",
      "review_level": "The copies, SHA values and methodological principles retained from 1585 were reused as historical material. This is not new reading of full methodological texts, application of an official tool or clinical certification in this review."
    }
  ],
  "status_dictionary": {
    "Met": "The relevant criterion was verified within this question and the retained scope. This does not establish efficacy.",
    "Partly verified": "Some records are verified, while gaps in direct criteria/data remain.",
    "Unverified": "The required direct values/criteria have not been verified within the current scope.",
    "Not met": "The population/ingredient/endpoint in the currently verified material does not match the selected direct criteria.",
    "Conflicting information": "This is a wording discrepancy within the same report, explicitly recorded in the original retained record. It is not independent verification of the original full text in this review.",
    "Not read": "The relevant external material was not actually read in this review."
  },
  "study_overlap": {
    "state": "These are links among reports in the stored manuscript. FAM-GOLDING-2014 (S01): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-OLAPARIB-NCT04024254 (S02, S10): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-CLARKE-2010 (S03): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-SHEEHY-1961 (S04): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / OFFICIAL-ODS-FOLATE (S05): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-OBEID-2017 (S06): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-NOZARI-2019 (S07): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / OFFICIAL-BSH-STATUS (S08): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / OFFICIAL-NICE-NG239 (S09): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / OFFICIAL-FOLIC-ACID-LABEL (S11): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / OFFICIAL-SWISS-FOLATE-HTA (S12): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-LASSI-PREGNANCY-REVIEW (S13): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. Human data exist, but directly eligible Hb results remain unverified within the retained review. This does not mean a worldwide absence of research or an effect of 0. Family labels are not summed as independent trial counts or participant counts.",
    "unique_trial_count": null,
    "unique_participant_count": null,
    "reason": "These are links among reports in the stored manuscript. FAM-GOLDING-2014 (S01): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-OLAPARIB-NCT04024254 (S02, S10): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-CLARKE-2010 (S03): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-SHEEHY-1961 (S04): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / OFFICIAL-ODS-FOLATE (S05): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-OBEID-2017 (S06): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-NOZARI-2019 (S07): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / OFFICIAL-BSH-STATUS (S08): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / OFFICIAL-NICE-NG239 (S09): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / OFFICIAL-FOLIC-ACID-LABEL (S11): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / OFFICIAL-SWISS-FOLATE-HTA (S12): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. / FAM-LASSI-PREGNANCY-REVIEW (S13): The current evidence study_id was linked to bibliographic relationships, shared registrations and historical reused citations. No inferences were made about an absent collection or the number of direct studies. Human data exist, but directly eligible Hb results remain unverified within the retained review. This does not mean a worldwide absence of research or an effect of 0. Family labels are not summed as independent trial counts or participant counts."
  },
  "history": [
    {
      "date": "2026-11-05",
      "kind": "Separation of public-facing display and data",
      "view_version": "1.0",
      "change": "The public-facing display and data were prepared from the existing 38 items. No new clinical search, change in verification status or scoring was performed."
    }
  ],
  "language": "en",
  "translation_date": "2026-11-05"
}