{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3098-main", "verdict_number": "3098", "title": "Oral supplemental or medicinal vitamin B6 exposure × risk of new or worsened clinical sensory neuropathy", "view_version": "1.0", "view_created_date": "2026-11-02", "criteria_version": "NGM-v3098-ORAL-B6-CLINICAL-SENSORY-NEUROPATHY-HARM-1.1", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-15", "review_scope": { "materials_read": "Archived Korean and English manuscripts and case-specific condition 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. Historical access records are distinguished from the reading of archived summaries in this review. Original judgments, numerical values, and unverified matters were preserved, with no new searches, calculations, or reassessment.", "date_meaning": "This is the date the archived material was checked, not the date of a search for the latest clinical literature." }, "claim_context": { "population": "Primarily adults with oral B6 exposure; healthy volunteers, people with pre-existing neuropathy, tuberculosis/HIV, and older cases are distinguished. Individual risk rates in children, pregnancy, and kidney disease are unverified", "intervention": "Vitamin B6 exposure: pyridoxine, pyridoxine hydrochloride, pyridoxal, PLP/P5P, and pyridoxamine are distinguished by form; causality is clearest for high-dose pyridoxine · Oral exposure. Parenteral or animal dosing is not extrapolated to human incidence after oral exposure · Single-ingredient tablets/capsules and combination products are distinguished. Exact salt, brand, release formulation, purity, and batch are unverified in many cases; these are not treated as identical formulations", "dose": "Exposure is preserved by study, without combining it into a general risk dose. Low-dose reports and high-dose experiments are distinguished; total amounts and measured verification of labeled amounts remain unverified when not established", "comparator": "Comparisons with no exposure or lower exposure are prioritized. Uncontrolled experiments and spontaneous reports have no comparator; the CIAP case-control study and tuberculosis dose comparison have separate contexts", "endpoint": "New or worsened clinical sensory neuropathy. Studies unable to separate these outcomes are labeled as having a mixed endpoint; changes in PLP/QST/nerve conduction alone are excluded", "duration": "Onset, duration of use, and follow-up after withdrawal are distinguished by study. The minimum duration associated with risk at low doses and several individual exposure durations are unverified", "excluded_extensions": "Excluded are changes in test markers alone; efficacy for treatment of pre-existing disease/attributing neuropathy from all causes to the exposure; conversion of report counts into incidence rates; claims of no risk for all vitamers/low doses; and conversion of regulatory criteria into biological thresholds/personal doses." }, "requirements": [ { "item_id": "N01", "question_type": "Safety contract", "question": "Were the original safety-only designation and the contract that efficacy is not applicable preserved?", "needed": "Original safety designation, assessment contract, and document-quality metadata", "role": "Required", "role_reason": "Required to avoid mixing the original warning for the harm question with the meanings of efficacy/document quality.", "application_exception": "The original grade ?, empty score value, document quality B, and empty axis_notes are not converted into new efficacy/risk scores.", "criterion": "Preserve the links between safety_only true, efficacy not_applicable, framework false, and the original values/absences, without assigning an efficacy badge or total score.", "basis": "C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user-defined scope and internal design / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied / E10: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid mixing the original warning for the harm question with the meanings of efficacy/document quality. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare the display fields with the technical preservation of the original safety/non-efficacy contract.", "current_reports": [], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The original question type is safety and safety_only is true. efficacy_grade/score are not_applicable, efficacy_framework_applied is false, grade is ?, and score is an empty value. axis_notes is an empty object, and the axes/no_human keys are absent. Document quality B is not a harm grade.", "condition_status": "Met", "status_reason": "The narrow condition for preserving the display was verified. Only the original warning, non-applicability of efficacy, and historical values were retained, with no new risk judgment.", "missingness": "Efficacy grades and scores are not applicable.", "uncertainty": "Efficacy grades and scores are not applicable. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original safety designation, assessment contract, and document-quality metadata" }, { "item_id": "N02", "question_type": "Claim boundaries", "question": "Was the separate question of oral B6 and new or worsened clinical sensory neuropathy fixed?", "needed": "Original claim, population/exposure, route, and endpoint boundaries", "role": "Required", "role_reason": "Required to distinguish the harm claim from questions about efficacy for treating pre-existing neuropathy or changes in test results.", "application_exception": "The scope is not extended to food/parenteral exposure, animals, changes in test values alone, or all neuropathy from other causes.", "criterion": "Link the original claim to oral supplement/medicine exposure and clinical new-onset/worsening endpoints, and specify the exclusions.", "basis": "C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: required to distinguish the harm claim from questions about efficacy for treating pre-existing neuropathy or changes in test results. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare the roles of material on other routes, treatment of pre-existing disease, and changes in test results against the eligibility boundaries.", "current_reports": [], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The current /ko/effect concerns the risk of new or worsened clinical sensory neuropathy. The main exposure is oral B6 from supplements/medicines in adults; ordinary/fortified foods, parenteral/animal material, and changes in PLP/QST/nerve conduction alone are distinguished separately.", "condition_status": "Met", "status_reason": "The inclusion/exclusion conditions for the separate harm question were linked to the actual facet. Clinical treatment efficacy or individual risk rates were not newly assessed.", "missingness": "These are not suitable for consolidation into a single risk rate.", "uncertainty": "These are not suitable for consolidation into a single risk rate. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original claim, population/exposure, route, and endpoint boundaries" }, { "item_id": "N03", "question_type": "Vitamer identity", "question": "Are the B6 vitamer, salt, and formulation identities established for each source?", "needed": "Original formulation composition, vitamer/salt, and product description", "role": "Required", "role_reason": "Required to avoid combining different exposures, such as pyridoxine, its hydrochloride, and PLP/P5P, as having the same toxic potency.", "application_exception": "Material reporting only pyridoxine is not filled in as the hydrochloride, and absence of risk for PLP is not inferred.", "criterion": "Verify the substance and salt actually reported in each source, and leave detailed identity unverified where it is unavailable.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Rationale for application to this case: required to avoid combining different exposures, such as pyridoxine, its hydrochloride, and PLP/P5P, as having the same toxic potency. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare the reported substance and actual formulation composition by vitamer.", "current_reports": [ "S11", "S12", "S13", "S14", "S20", "S21", "S22" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The preserved manuscript distinguishes pyridoxine, pyridoxine hydrochloride, pyridoxal, PLP/P5P, and pyridoxamine. Although causality is clearest for high-dose pyridoxine, the exact salt in several sources is unverified, and no clinical guarantee that PLP is free of risk was verified.", "condition_status": "Partly verified", "status_reason": "The original boundaries distinguishing vitamers are present, but the salt identities/equivalence of risk of all actual formulations are not established.", "missingness": "Exact vitamer/salt and equivalence between formulations.", "uncertainty": "Exact vitamer/salt and equivalence between formulations. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original formulation composition, vitamer/salt, and product description" }, { "item_id": "N04", "question_type": "Product and actual exposure", "question": "Are the brand, batch, measured content, and actual dose taken verified?", "needed": "Manufacturing/labeling, batch, measured content, and dosing frequency/adherence records", "role": "Required", "role_reason": "Required to avoid generalizing a nominal administered dose into actual intake or risk for the entire product.", "application_exception": "The labeled tablet/capsule amount is not treated as verification of purity, batch/release, dosing frequency, or adherence.", "criterion": "Verify the exact product, ingredients/release, measured content, and actual dosing frequency/adherence, and identify the remaining gaps.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Rationale for application to this case: required to avoid generalizing a nominal administered dose into actual intake or risk for the entire product. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review whether product information agrees with individual intake records.", "current_reports": [ "S20", "S21", "S22", "S24", "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Single-ingredient tablets/capsules and combination products are distinguished, but the exact brand, release formulation, purity, batch, measured content versus labeled amount, and actual dosing frequency/total duration are unverified in several sources. These gaps were not filled in as identical formulations or actual total intake.", "condition_status": "Unverified", "status_reason": "The currently preserved content explicitly states that these detailed identities and actual amounts used cannot be established.", "missingness": "Product/batch, measured amount, frequency, and adherence/duration.", "uncertainty": "Product/batch, measured amount, frequency, and adherence/duration. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Manufacturing/labeling, batch, measured content, and dosing frequency/adherence records" }, { "item_id": "N05", "question_type": "Multiple products and units", "question": "Can content per tablet be distinguished from actual total daily intake across multiple products?", "needed": "Product-specific content units, dosing frequency/number taken, and concurrent-exposure table", "role": "Required", "role_reason": "Required to avoid converting Lareb's per-tablet content or reports involving multiple products into a daily dose/risk threshold.", "application_exception": "1.4–100 mg is a per-tablet amount, and the TGA's 9 reports involving multiple products are not an independent group with verified total daily intake.", "criterion": "Link content units, number of products, dosing frequency, and background intake, without calculating totals that have not been verified.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Rationale for application to this case: required to avoid converting Lareb's per-tablet content or reports involving multiple products into a daily dose/risk threshold. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare the data units for per-tablet content, per-product content, and total daily intake.", "current_reports": [ "S11", "S21", "S22" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "In the 2018 Lareb abstract, 1.4–100 mg is the content per tablet. Of the TGA's 32 selected reports, 9 involved multiple products. Daily total or cumulative intake was not calculated using unverified dosing frequency/measured amounts and overlapping categories.", "condition_status": "Partly verified", "status_reason": "The units and the signal involving multiple products are known, but components needed to establish individual actual total/cumulative intake are insufficient.", "missingness": "All products, measured/labeled amounts, dosing frequency, and duration for each individual.", "uncertainty": "All products, measured/labeled amounts, dosing frequency, and duration for each individual. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Product-specific content units, dosing frequency/number taken, and concurrent-exposure table" }, { "item_id": "N06", "question_type": "Exposure route", "question": "Was oral exposure from supplements/medicines separated from other routes/foods?", "needed": "Original route, exposure source, and applicability of related material", "role": "Required", "role_reason": "Required to avoid transferring human incidence after oral exposure across routes and exposure sources.", "application_exception": "Ordinary/fortified foods, parenteral dosing, and animal dosing are not evidence of identical risk for exposure to these formulations.", "criterion": "Preserve the original exposure strata for oral supplements/medicines and prevent direct extrapolation from other routes.", "basis": "C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: required to avoid transferring human incidence after oral exposure across routes and exposure sources. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare directness/exclusions according to the original route and exposure stratum.", "current_reports": [], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The facets concern B6 from oral supplements/medicines, with ordinary/fortified foods kept as separate exposure strata. Parenteral/animal doses are not extrapolated to human incidence after oral exposure.", "condition_status": "Met", "status_reason": "The condition preserving the actual route and exposure-source boundaries was verified. New harm from other routes was not assessed.", "missingness": "An identical risk rate for material outside the specified route is unverified.", "uncertainty": "An identical risk rate for material outside the specified route is unverified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original route, exposure source, and applicability of related material" }, { "item_id": "N07", "question_type": "Population and baseline status", "question": "Are the population, pre-exposure neuropathy, and underlying diseases verified for each source?", "needed": "Table of inclusion/exclusion, baseline symptoms, examination/disease, renal/hepatic status, and medications", "role": "Required", "role_reason": "Required to avoid combining healthy volunteers, people with existing CIAP, TB/HIV, and older adults into the same population for new-onset events.", "application_exception": "The category of predominantly adults is not converted into normal individual baseline status or safety for special populations.", "criterion": "Link the study-specific population, baseline neuropathy, renal/hepatic status, medications, and selection status, and explicitly identify omissions.", "basis": "C04: M03 §3.2.1; detailed population conditions are internally designed / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed / H08: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid combining healthy volunteers, people with existing CIAP, TB/HIV, and older adults into the same population for new-onset events. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review applicability limitations related to baseline risk and population selection.", "current_reports": [ "S20", "S23", "S24", "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The 5 healthy volunteers, existing CIAP patients/controls, TB cohort treated with terizidone, and 3 older cases represent different populations. Individual baseline renal/hepatic function, medications, and classification as new onset/worsening of existing disease are unverified in several sources.", "condition_status": "Partly verified", "status_reason": "The main population contexts are available, but there is no material fully verifying individual baseline status/selection and pre-existing neuropathy.", "missingness": "Baseline clinical status, selection, vulnerability, and individual medications.", "uncertainty": "Baseline clinical status, selection, vulnerability, and individual medications. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Table of inclusion/exclusion, baseline symptoms, examination/disease, renal/hepatic status, and medications" }, { "item_id": "N08", "question_type": "Clinical event definition", "question": "Was clinical sensory neuropathy confirmed/ascertained separately from test markers?", "needed": "Original diagnostic criteria, symptoms/examination, QST/conduction, and detection/blinding procedures", "role": "Required", "role_reason": "Required to avoid substituting changes in PLP/QST/conduction or high blood B6 values for clinical occurrence.", "application_exception": "Participants with changes in test results alone and no clinical symptoms are not included as clinical events.", "criterion": "Verify symptoms, signs/examination, and confirmation/ascertainment procedures, and separate changes in markers alone from clinical events.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / E03: M08 Table 8.2.a, M03 §3.2.4; internal application / E09: M03 §3.2.4; internally defined extension boundaries / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed. Rationale for application to this case: required to avoid substituting changes in PLP/QST/conduction or high blood B6 values for clinical occurrence. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare clinical event definitions with differences in measurement/detection of test markers.", "current_reports": [ "S14", "S20", "S21", "S22", "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Clinical new onset/worsening is the primary endpoint, and changes in PLP/QST/nerve conduction alone are excluded. A conflict in the clinical numerator between Berger and EFSA's individual-level extraction and the lack of consistent clinical confirmation in Lareb remain; all participants/reports therefore cannot be treated as equally confirmed events.", "condition_status": "Partly verified", "status_reason": "The boundary between clinical events and test findings is defined, but complete comparability/confirmation of diagnosis and ascertainment across sources is unverified.", "missingness": "Diagnosis/clinical event table, detection/blinding, and independent interpretation.", "uncertainty": "Diagnosis/clinical event table, detection/blinding, and independent interpretation. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original diagnostic criteria, symptoms/examination, QST/conduction, and detection/blinding procedures" }, { "item_id": "N09", "question_type": "Distinguishing new onset from worsening", "question": "Can new onset and worsening of pre-existing symptoms be distinguished separately?", "needed": "Table of baseline symptoms, event counts for new onset/worsening, populations at risk, and timing", "role": "Required", "role_reason": "Required to avoid converting results for a mixed endpoint into a single incidence rate of new toxicity.", "application_exception": "The mixture of new onset/worsening in the TB cohort or incomplete classification in spontaneous reports is not filled in as separately available values.", "criterion": "Verify pre-exposure symptoms and events, denominators, and timing for new onset/worsening, and leave mixed outcomes as mixed.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H04: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid converting results for a mixed endpoint into a single incidence rate of new toxicity. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Trace pre-existing disease and the classification of events before and after exposure.", "current_reports": [ "S21", "S22", "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The original facet labels material unable to separate the outcomes as having a mixed endpoint. Court's 50 people constitute a mixture of new onset/worsening, and the respective event counts were not verified in the abstract. Lareb also has gaps in clinical confirmation and the distinction between new onset/worsening.", "condition_status": "Unverified", "status_reason": "The current archived material cannot establish all separate event counts and denominators for new onset/worsening.", "missingness": "Original events, denominators, and baseline status for new onset/worsening separately.", "uncertainty": "Original events, denominators, and baseline status for new onset/worsening separately. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Table of baseline symptoms, event counts for new onset/worsening, populations at risk, and timing" }, { "item_id": "N10", "question_type": "High-dose exposure", "question": "Were Berger's reported doses separated from observations of onset and after withdrawal?", "needed": "Original table of dosing/onset and follow-up after withdrawal", "role": "Required", "role_reason": "Required to avoid extending temporal relationships at high doses to low doses generally/all users.", "application_exception": "1 or 3 g/day is not converted into a general recommended dose, minimum risk dose, or individual actual cumulative exposure.", "criterion": "Attribute the 5 volunteers, reported pyridoxine doses of 1 or 3 g/day, earlier onset, and worsening for 2–3 weeks after withdrawal to their original locations.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / H02: Design-specific harm questions in M19 §19.2; temporal-relationship details are internally designed. Rationale for application to this case: required to avoid extending temporal relationships at high doses to low doses generally/all users. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare dose, time to onset, and the course after exposure withdrawal separately.", "current_reports": [ "S20", "S14" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Berger is an uncontrolled prospective exposure study in which 5 volunteers received pyridoxine at 1 or 3 g/day. The preserved account states that symptoms appeared earlier at the higher dose and worsening could continue for 2–3 weeks after withdrawal. Individual cumulative exposure was not calculated.", "condition_status": "Met", "status_reason": "The narrow attribution of reported doses and temporal relationships was verified. Clinical event counts/population incidence remain subject to separate unverified/conflicting conditions.", "missingness": "Individual actual exposure duration/cumulative exposure and the clinical numerator are separate gaps.", "uncertainty": "Individual actual exposure duration/cumulative exposure and the clinical numerator are separate gaps. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original table of dosing/onset and follow-up after withdrawal" }, { "item_id": "N11", "question_type": "Conflict in the clinical numerator", "question": "Is Berger's actual number of clinical cases consistently verified across sources?", "needed": "Correspondence between the original abstract, individual clinical symptom/test table, and EFSA extraction", "role": "Required", "role_reason": "Required to avoid automatically interpreting the denominator of 5 volunteers as 5/5 clinical occurrence.", "application_exception": "Distinguish successful recording of the conflict as it stands from a status in which the clinical numerator has been consistently verified.", "criterion": "Compare symptom/test criteria and clinical numerators in the original abstract and EFSA's individual-participant extraction. If disagreement remains, do not treat the numerator as established or claim 100% occurrence.", "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H04: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: required to avoid automatically interpreting the denominator of 5 volunteers as 5/5 clinical occurrence. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review correspondence of participants/clinical criteria across sources and the disagreement in numerators.", "current_reports": [ "S20", "S14" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The broad description in Berger's abstract and EFSA's individual-participant extraction disagree on the number of people with onset of clinical symptoms. The EFSA table includes participants with changes in sensory testing alone and no clinical symptoms; therefore, 5/5 or 100% occurrence is not claimed.", "condition_status": "Conflicting information", "status_reason": "Descriptions of the same clinical occurrence disagree, so a single numerator cannot be established. This descriptive conflict was not resolved through a new causality judgment.", "missingness": "Resolution of conflicts concerning the individual clinical numerator, diagnostic confirmation criteria, and correspondence between extractions.", "uncertainty": "Resolution of conflicts concerning the individual clinical numerator, diagnostic confirmation criteria, and correspondence between extractions. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Correspondence between the original abstract, individual clinical symptom/test table, and EFSA extraction" }, { "item_id": "N12", "question_type": "Actual comparator", "question": "Were the uncontrolled design of the high-dose experiment and the boundaries of comparative risk preserved?", "needed": "Original design, comparator/allocation, and exposure table", "role": "Required", "role_reason": "Required to avoid converting the temporal relationship of prospective exposure into a randomized comparison with no exposure or a population risk rate.", "application_exception": "Observations at the alternative doses 1 or 3 g are not treated as an RCT effect with an unexposed control.", "criterion": "Explicitly identify the uncontrolled prospective high-dose design and distinguish it from estimation of population incidence/RR.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation to testing are internally designed / E01: M08 §8.1–8.2.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application. Rationale for application to this case: required to avoid converting the temporal relationship of prospective exposure into a randomized comparison with no exposure or a population risk rate. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review the scope of causal/risk interpretation permitted by the design and actual comparison conditions.", "current_reports": [ "S20", "S14" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Berger is a small prospective high-dose exposure study without an unexposed control. The original weight explicitly states that it serves as evidence for causality of high-dose pyridoxine but is not used as population incidence. This table does not convert it into an RCT or an RR for general users.", "condition_status": "Met", "status_reason": "The condition for preserving the actual design and original interpretation limitations was verified. High-dose causality was not newly certified, and comparative risk was not calculated.", "missingness": "An unexposed comparison and quantitative risk for general users remain separately unverified.", "uncertainty": "An unexposed comparison and quantitative risk for general users remain separately unverified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original design, comparator/allocation, and exposure table" }, { "item_id": "N13", "question_type": "Recovery and rechallenge", "question": "Are recovery/worsening after withdrawal and the actual course on rechallenge verified?", "needed": "Original individual event records for withdrawal, follow-up/function, and rechallenge", "role": "Required", "role_reason": "Required to avoid extending some improvement into complete recovery for everyone or confirmation through rechallenge.", "application_exception": "Coasting, persistent disability, and cases of recovery after withdrawal are not converted into a guarantee of individual recovery or a probability of permanent damage.", "criterion": "Verify withdrawal/course, completeness of recovery, and rechallenge for each individual, and retain the areas with insufficient information.", "basis": "H02: Design-specific harm questions in M19 §19.2; temporal-relationship details are internally designed / H08: M19 §19.1.2–19.2.4; internal application / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: required to avoid extending some improvement into complete recovery for everyone or confirmation through rechallenge. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare onset and changes after withdrawal with alternative causes/completeness of follow-up.", "current_reports": [ "S14", "S20", "S24", "S26" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Official assessments include cases of improvement after withdrawal, but the speed/completeness of recovery is not guaranteed. Worsening for 2–3 weeks after withdrawal of high-dose exposure and the possibility of long-term disability are both preserved. Sufficient individual rechallenge data were not verified in this extraction.", "condition_status": "Partly verified", "status_reason": "Some post-withdrawal courses are available, but individual recovery/confirmation through rechallenge and complete follow-up cannot be established.", "missingness": "Individual recovery, rechallenge, and completeness of follow-up.", "uncertainty": "Individual recovery, rechallenge, and completeness of follow-up. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original individual event records for withdrawal, follow-up/function, and rechallenge" }, { "item_id": "N14", "question_type": "Overlap within a reporting series", "question": "Are the independence and overlap relationships of Lareb reports verified?", "needed": "Original report identifiers, collection period, and overlap/re-citation correspondence table", "role": "Required", "role_reason": "Required to avoid adding the 2018/2025/EFSA interim counts as independent reports/trials.", "application_exception": "90 and 224 overlap within the same reporting series, and official re-citations are not separate replications in humans.", "criterion": "Link the series, collection period, and overlap relationships, and do not sum counts when individual overlap/independent events are unverified.", "basis": "C02: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; internal application / H07: M04 §4.6.1–4.6.2; adaptation to harm material is internally designed. Rationale for application to this case: required to avoid adding the 2018/2025/EFSA interim counts as independent reports/trials. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare the relationship between reanalysis of the same reports and new independent events.", "current_reports": [ "S21", "S22", "S14" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The 2025 Lareb analysis includes 224 reports and overlaps within the same series with the 2018 count of 90 reports and EFSA's interim counts. The original evidence groups them under F-LAREB and does not sum them. The current archived summary does not contain a table of independent events with individual report overlap resolved.", "condition_status": "Partly verified", "status_reason": "Overlap within the series is explicitly stated, but no material fully establishes the correspondence of independence/overlap at the individual-report level.", "missingness": "Individual report identification and correspondence of overlapping/independent reports.", "uncertainty": "Individual report identification and correspondence of overlapping/independent reports. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original report identifiers, collection period, and overlap/re-citation correspondence table" }, { "item_id": "N15", "question_type": "Collection period and reference date", "question": "Were the Lareb collection period and the historical reference dates of the material separated?", "needed": "Original analysis collection window and publication/review metadata", "role": "Required", "role_reason": "Required to avoid changing the end date of report collection into the publication/review date or the date of this lookup.", "application_exception": "The report collection end on 2023-12-31, the 2025 analysis, the original review on 2026-09-15, and the date of this review are different events.", "criterion": "Preserve the 2025 analysis's report collection window, 2007-08–2023-12-31, separately from publication/review dates.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user-defined scope and internal design / H02: Design-specific harm questions in M19 §19.2; temporal-relationship details are internally designed. Rationale for application to this case: required to avoid changing the end date of report collection into the publication/review date or the date of this lookup. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare the actual event associated with each date and the applicability of the material.", "current_reports": [ "S22" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The manuscript's 2025 Lareb analysis covers reports collected from 2007-08 through 2023-12-31, with 224 reports. The original verified_date is 2026-09-15, distinguished from the local archived-summary review date of 2026-10-05 and the actual report collection window.", "condition_status": "Met", "status_reason": "Only the attribution of the original collection period and dates to their events was verified. This did not involve looking up the latest external reports/official regulations.", "missingness": "The current latest report collection window/individual exposure durations were not newly verified.", "uncertainty": "The current latest report collection window/individual exposure durations were not newly verified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original analysis collection window and publication/review metadata" }, { "item_id": "N16", "question_type": "Report confirmation and duration", "question": "Are clinical confirmation, actual exposure duration, and completeness of collection of Lareb reports verified?", "needed": "Original report table of diagnosis/exposure/duration, detection/selection, and follow-up", "role": "Required", "role_reason": "Required to avoid treating reported neuropathy as consistently confirmed new-onset events.", "application_exception": "Blood B6 values or titles are not used to substitute for gaps in report selection, diagnosis, or exposure.", "criterion": "Check the clinical definition/confirmation, exposure/onset periods, alternative causes, and missed detection for each report.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H02: M19 §19.2 design-specific harm questions; details of temporal relationships are internally designed / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Rationale for application to this case: needed to avoid treating reported neuropathy as consistently confirmed new clinical events. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review reporting definitions, selection/detection processes, and individual temporal relationships.", "current_reports": [ "S21", "S22" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Lareb provides a safety signal from spontaneously reported neuropathy. The original evidence/manuscript states that consistent clinical confirmation, actual daily amounts/durations, and separation of new from worsened cases are incomplete. Blood values alone do not establish clinical toxicity in each report.", "condition_status": "Unverified", "status_reason": "The currently retained materials contain no original table that would establish confirmation, actual timing, or completeness of detection for each report.", "missingness": "Clinical confirmation, exposure/duration, and collection/follow-up for each report.", "uncertainty": "Clinical confirmation, exposure/duration, and collection/follow-up for each report. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original report table of diagnosis/exposure/duration, detection/selection, and follow-up" }, { "item_id": "N17", "question_type": "Exposed-person denominator for reports", "question": "Is a denominator verified for calculating incidence among exposed persons from spontaneous reports?", "needed": "Data on all exposed persons, observation time by dose, all/confirmed events, and unreported cases", "role": "Required", "role_reason": "Needed to avoid converting report counts into probabilities of occurrence among all users or dose groups.", "application_exception": "Report counts, counts of blood tests, and content per tablet are not exposed-person counts or person-time.", "criterion": "Do not present incidence unless all exposed persons, observation time, and event counts for the same event/dose/duration have been verified.", "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting report counts into probabilities of occurrence among all users or dose groups. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review the correspondence between report-based counts and the actual population at risk/observation time.", "current_reports": [ "S21", "S22", "S11" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Lareb’s 224 reports and TGA’s 32 reports are report counts. The manuscript states that incidence is not calculated because an exposed-person denominator and consistent clinical confirmation/duration are absent. This table also calculates neither report proportions nor incidence.", "condition_status": "Unverified", "status_reason": "Without a population-at-risk denominator and duration, report counts cannot establish incidence among exposed persons.", "missingness": "Exposed-person denominator, observation time, and completeness of reporting/confirmation.", "uncertainty": "Exposed-person denominator, observation time, and completeness of reporting/confirmation. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Data on all exposed persons, observation time by dose, all/confirmed events, and unreported cases" }, { "item_id": "N18", "question_type": "TGA selected-report signal", "question": "Can selection and overlap in TGA’s 32 reports and low-dose/multiple-product categories be verified?", "needed": "Original TGA tables of report selection, clinical confirmation, and overlap between dose/multiple-product categories", "role": "Required", "role_reason": "Needed to avoid mistaking the composition of selected reports for comparative risk among all users by dose.", "application_exception": "The 21 reports and 9 reports may overlap; the 32 reports are not substituted for all reports/exposed persons or fully confirmed events.", "criterion": "Verify the selection criteria, categories/overlap, and actual denominator meanings of 32·21·9, while retaining unverified selection processes as unverified.", "basis": "C04: M03 §3.2.1; detailed population conditions are internally designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / H04: M19 §19.1.2–19.2.4; internal application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Rationale for application to this case: needed to avoid mistaking the composition of selected reports for comparative risk among all users by dose. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare selection criteria, category overlap, and detection/reporting bias.", "current_reports": [ "S11", "S12" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Through 2022-08-05, TGA reported 32 selected reports, of which 21 involved 50 mg/day or less and 9 involved use of multiple products. The categories may overlap. These describe the composition of reports, not the probability of occurrence among users at those doses; an individual-level selection/overlap table is absent from the retained archived summaries.", "condition_status": "Partly verified", "status_reason": "The selected report counts/categories and possibility of overlap are known, but the complete selection, confirmation, and overlap correspondence cannot be established.", "missingness": "Records of selection/clinical confirmation, category overlap, and omissions.", "uncertainty": "Records of selection/clinical confirmation, category overlap, and omissions. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original TGA tables of report selection, clinical confirmation, and overlap between dose/multiple-product categories" }, { "item_id": "N19", "question_type": "Low-dose causality", "question": "Are comparative risk, causality, and a no-risk boundary at low doses established?", "needed": "Exposure/comparator, event, duration, confounding, and risk-estimate data for each low dose", "role": "Required", "role_reason": "Needed to avoid converting a possible signal from low-dose reports into confirmed causality at all low doses or safety at all low doses.", "application_exception": "The composition of reports involving ≤50 mg/day and the labeling warning for >10 mg are not the same biological threshold.", "criterion": "Retain the scope of dose-specific risk verification based on actual comparators/denominators, precise exposure, other causes/duration, and clinical events.", "basis": "H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting a possible signal from low-dose reports into confirmed causality at all low doses or safety at all low doses. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Distinguish the evidentiary level of spontaneous-report signals from that of comparative-risk/causal conclusions.", "current_reports": [ "S11", "S12", "S14" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Low-dose spontaneous reports constitute a possible signal, but a minimum risk dose/duration and an individual no-risk boundary have not been verified. The manuscript avoids both confirming causality at all low doses and declaring all low doses safe, and distinguishes these questions from labeling-warning criteria.", "condition_status": "Unverified", "status_reason": "Without actual comparative/denominator, exposure, and confirmation data, a causal risk or no-risk boundary applicable to all low doses cannot be established.", "missingness": "Precise exposure, comparators, denominators/durations, and clinical/confounding data by dose.", "uncertainty": "Precise exposure, comparators, denominators/durations, and clinical/confounding data by dose. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Exposure/comparator, event, duration, confounding, and risk-estimate data for each low dose" }, { "item_id": "N20", "question_type": "TB comparative estimate", "question": "Are the dose-specific comparative estimate and its uncertainty in the tuberculosis cohort verified?", "needed": "Tables of exposure/events, denominators, adjustment models, HR/CI, and follow-up by dose group", "role": "Required", "role_reason": "Needed to avoid transferring the reported HR to a causal RR for general supplement use or an exact incidence rate.", "application_exception": "The 144 people and 50 people (35% in the original) and HR 2.79 do not substitute for group-specific denominators/event counts or CI.", "criterion": "Distinguish the 200 versus 150 mg/day comparison and adjusted HR/P from the actual scope of verification of group-specific denominators/events, CI, and follow-up.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / E04: M08 §8.2.2, M15 §15.3.1; internal application / E05: M15 §15.3.1–15.3.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: needed to avoid transferring the reported HR to a causal RR for general supplement use or an exact incidence rate. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare estimates and uncertainty for the same event/comparator/duration and analysis model.", "current_reports": [ "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Court is a terizidone-treatment cohort with 144 people recruited and neuropathy in 50 people (35% in the original). The comparison of 200 versus 150 mg/day retains an adjusted HR of 2.79, P = 0.01, for a mixed new/worsened endpoint. Group-specific denominators/event counts, the HR CI, and exact follow-up duration were not verified from the abstract.", "condition_status": "Partly verified", "status_reason": "The nominal-dose comparison and reported HR/P are available, but group-specific denominators and CI/duration are insufficient. No new CI/RR/proportion was calculated.", "missingness": "Group-specific events, denominators, HR CI, and follow-up/analysis tables.", "uncertainty": "Group-specific events, denominators, HR CI, and follow-up/analysis tables. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Tables of exposure/events, denominators, adjustment models, HR/CI, and follow-up by dose group" }, { "item_id": "N21", "question_type": "TB nonrandomized design", "question": "Were the nonrandomized doses in the tuberculosis cohort and limitations on application to general supplement use preserved?", "needed": "Original recruitment/prescribing, population/concurrent treatment, and actual comparator design", "role": "Required", "role_reason": "Needed to avoid converting a nonrandomized comparison in a treatment setting into an RCT causal effect among healthy users.", "application_exception": "Do not equate the TB/HIV and terizidone/cycloserine context with general exposure to a single-ingredient supplement.", "criterion": "Indicate the original design, population/co-medication, and nonrandomized doses, and prevent transfer of the HR to an RR for general users.", "basis": "C04: M03 §3.2.1; detailed population conditions are internally designed / E01: M08 §8.1–8.2.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed. Rationale for application to this case: needed to avoid converting a nonrandomized comparison in a treatment setting into an RCT causal effect among healthy users. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review the interpretive scope arising from the population, prescribing context, and nonrandomized comparison.", "current_reports": [ "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The original design is a prospective cohort of multidrug-resistant tuberculosis treated with terizidone; B6 doses are nonrandomized. HIV, tuberculosis, co-medications, and prescribing reasons are intertwined, so the retained HR is not transferred to a causal RR for general supplement users.", "condition_status": "Met", "status_reason": "The condition of preserving the actual nonrandomized context and original generalizability limitations was verified. This is not a judgment that confounding was eliminated.", "missingness": "A separate causal comparative risk for general supplement users is unverified.", "uncertainty": "A separate causal comparative risk for general supplement users is unverified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original recruitment/prescribing, population/concurrent treatment, and actual comparator design" }, { "item_id": "N22", "question_type": "TB alternative explanations", "question": "Was confounding by tuberculosis/HIV, medications, and prescribing reasons sufficiently controlled?", "needed": "Original adjustment-model, prescribing/underlying-disease, medication, and exposure-follow-up data", "role": "Required", "role_reason": "Needed to avoid establishing the association with B6 dose as a cause independent of medications and diseases.", "application_exception": "The term adjusted HR alone does not eliminate residual confounding from prescribing indications, baseline neuropathy, or disease/co-medication.", "criterion": "Check model variables, prescribing reasons, baseline status/concurrent medications, exposure deviations, and residual confounding.", "basis": "H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / C04: M03 §3.2.1; detailed population conditions are internally designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application. Rationale for application to this case: needed to avoid establishing the association with B6 dose as a cause independent of medications and diseases. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review actual measurement of adjustment variables and confounding associated with timing and prescribing.", "current_reports": [ "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The manuscript retains the intertwined roles of HIV, TB, co-medications, and prescribing reasons. The reported HR was verified in the abstract, but all adjustment variables, baseline neuropathy, prescribing/adherence, and disease roles cannot be established from the retained archived summaries.", "condition_status": "Unverified", "status_reason": "Adjustment tables and actual baseline/prescribing data are insufficient to establish the extent of control for alternative causes other than B6.", "missingness": "Adjustment models, baseline/prescribing factors, concurrent exposures, and residual confounding.", "uncertainty": "Adjustment models, baseline/prescribing factors, concurrent exposures, and residual confounding. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original adjustment-model, prescribing/underlying-disease, medication, and exposure-follow-up data" }, { "item_id": "N23", "question_type": "TB endpoint and time denominator", "question": "Can the endpoint/time denominator for TB neuropathy be separated from other neuropsychiatric AE?", "needed": "Neuropathy-specific tables of definitions/confirmation, events/time, and missing data/discontinuation", "role": "Required", "role_reason": "Needed to avoid transferring the person-month incidence of all neuropsychiatric AE to sensory neuropathy.", "application_exception": "The mixed new/worsened count of 50 people is not a separate count of clinically confirmed new events or an exposure-time denominator.", "criterion": "Separately verify the definition, new/worsened status, follow-up/denominator, and missing data for neuropathy, and prevent transfer of the composite AE incidence.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H04: M19 §19.1.2–19.2.4; internal application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Rationale for application to this case: needed to avoid transferring the person-month incidence of all neuropsychiatric AE to sensory neuropathy. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare attribution of the mixed endpoint, other AE, and observation time/participant flow.", "current_reports": [ "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Court’s outcome is a mixture of new or worsened peripheral neuropathy. Separate event counts and exact follow-up duration are unverified in the abstract. The person-month incidence of all neuropsychiatric AE was not used as the incidence of this clinical sensory neuropathy.", "condition_status": "Partly verified", "status_reason": "Boundaries for the mixed endpoint and exclusion of other AE are present, but event-specific definitions, separate counts/time, and participant flow are incomplete.", "missingness": "Separate neuropathy definitions/events, denominators, and duration/missing data.", "uncertainty": "Separate neuropathy definitions/events, denominators, and duration/missing data. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Neuropathy-specific tables of definitions/confirmation, events/time, and missing data/discontinuation" }, { "item_id": "N24", "question_type": "CIAP population applicability", "question": "Was pre-existing disease in the CIAP case-control study distinguished from the question of new toxicity?", "needed": "Original population/design, baseline symptoms, and exposure timing/endpoints", "role": "Required", "role_reason": "Needed to avoid converting the association between prevalent CIAP and supplement use into risk of new onset.", "application_exception": "The 381 cases and 140 controls are not a population-at-risk denominator for a cohort with new exposure.", "criterion": "Indicate the context of the pre-existing CIAP case-control study and its role, which does not establish incident toxicity or guarantee absence of risk.", "basis": "C04: M03 §3.2.1; detailed population conditions are internally designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting the association between prevalent CIAP and supplement use into risk of new onset. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare the directness of the prevalent-case case-control study for the new-onset question and assess reverse causation.", "current_reports": [ "S23" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Visser is a case-control study of 381 patients with pre-existing CIAP and 140 healthy controls. The original endpoint concerns an association with pre-existing disease, not incident toxicity. The original weight is preserved as limiting/contrary evidence and is not used as a causal incidence rate or a safety guarantee.", "condition_status": "Met", "status_reason": "The population/design for the association with pre-existing disease and the boundary against transferring it directly to new-onset risk were verified.", "missingness": "This study does not establish a direct comparative risk of new onset by exposure.", "uncertainty": "This study does not establish a direct comparative risk of new onset by exposure. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original population/design, baseline symptoms, and exposure timing/endpoints" }, { "item_id": "N25", "question_type": "Attribution of contrasting results", "question": "Were the nonsignificant blood-value result and the supplement-use association in CIAP both preserved?", "needed": "Original results tables, blood-value/supplement-use estimates, and authors’ interpretation", "role": "Required", "role_reason": "Needed to avoid omitting favorable/nonsignificant or contrary results and attributing all neuropathy to B6.", "application_exception": "Do not convert the blood-value P = 0.58 into a risk of 0, or the supplement-use OR into a causal RR for new toxicity.", "criterion": "Link the 381/140 participants’ 99/109 nmol/L values and P, the 31%/22% and OR/CI/P, and the authors’ limiting interpretation together according to their original locations.", "basis": "C08: M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid omitting favorable/nonsignificant or contrary results and attributing all neuropathy to B6. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare the results, directions, and uncertainties for different measurements/exposures separately.", "current_reports": [ "S23", "S14" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "In CIAP, the difference in median blood B6 values of 99 versus 109 nmol/L was nonsignificant at P = 0.58. Supplement use was 31% versus 22%, OR 1.7 (95% CI 1.0–2.7; P = 0.032). Considering daily amounts, cumulative amounts, duration, and blood values, the authors interpreted a causal association as unlikely. Both contrasting and limiting results are preserved.", "condition_status": "Met", "status_reason": "Reported values, attribution to different exposures/markers, and the authors’ limiting interpretation were linked together. No new causality/no-risk assessment was performed.", "missingness": "Original adjustment/baseline data beyond the scope of the abstract remain separately unverified.", "uncertainty": "Original adjustment/baseline data beyond the scope of the abstract remain separately unverified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original results tables, blood-value/supplement-use estimates, and authors’ interpretation" }, { "item_id": "N26", "question_type": "Reverse causation and underlying causes", "question": "Are reverse causation and alternative causes in CIAP and reports sufficiently verified?", "needed": "Baseline symptoms, start/sequence of use, examinations/other tests, and alternative diseases/medications", "role": "Required", "role_reason": "Needed to review the possibility that B6 was used because of pre-existing symptoms, and neuropathy due to other causes.", "application_exception": "Elevated PLP or supplement use alone does not establish B6 causation or the cause of pre-existing disease.", "criterion": "Check the temporal order of symptoms/exposure, underlying disease/concurrent medication, selection/measurement, and alternative causes.", "basis": "H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application / C04: M03 §3.2.1; detailed population conditions are internally designed. Rationale for application to this case: needed to review the possibility that B6 was used because of pre-existing symptoms, and neuropathy due to other causes. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review reverse causation/confounding associated with exposure timing and disease selection/detection.", "current_reports": [ "S23", "S14", "S21", "S22", "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The manuscript retains possible reverse causation from supplement use prompted by CIAP symptoms and the selected phenotype. Other causes, including diabetes, B12 deficiency, alcohol, kidney disease, and anticancer/TB medications, also need to be considered. Whether these alternatives were sufficiently excluded in each source is unverified.", "condition_status": "Unverified", "status_reason": "Specific data on temporal order/baseline status and alternative causes are insufficient to establish elimination of reverse causation/confounding.", "missingness": "Data on symptom/use sequence, alternative diseases/medications, and selection/detection.", "uncertainty": "Data on symptom/use sequence, alternative diseases/medications, and selection/detection. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Baseline symptoms, start/sequence of use, examinations/other tests, and alternative diseases/medications" }, { "item_id": "N27", "question_type": "Older-adult combination-product cases", "question": "Can the combination product and actual long-term exposure in 3 older adults be verified?", "needed": "Original case-specific product/composition, dose/duration, baseline-status, and adherence data", "role": "Required", "role_reason": "Needed to avoid combining cases involving B1/B6/B12 combination tablets into population incidence for single-ingredient B6 products.", "application_exception": "Ages 80·83·83 years in 3 people and 600 mg/day for 3–10 years do not constitute an exposed-person denominator for a single-ingredient product or an individual recommended dose.", "criterion": "Distinguish combination composition, nominal pyridoxine dose, and duration/population from gaps in actual product, adherence, and concurrent exposure data.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / H05: M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / H08: M19 §19.1.2–19.2.4; internal application. Rationale for application to this case: needed to avoid combining cases involving B1/B6/B12 combination tablets into population incidence for single-ingredient B6 products. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare actual exposure in each case and the combination-product/older-adult context.", "current_reports": [ "S24" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Kulkantrakorn is a case series of people aged 80·83·83 years, 3 in total, with sensory ataxic neuropathy/gait impairment. They used pyridoxine in B1/B6/B12 combination tablets at 600 mg/day for 3–10 years. The exact formulation, actual cumulative amount, and all underlying causes cannot be established from the current extraction.", "condition_status": "Partly verified", "status_reason": "The population, combination/nominal dose, and duration are available, but verification of detailed product information, actual use, and underlying causes is insufficient.", "missingness": "Case-specific combination composition, actual use/cumulative exposure, and underlying causes.", "uncertainty": "Case-specific combination composition, actual use/cumulative exposure, and underlying causes. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original case-specific product/composition, dose/duration, baseline-status, and adherence data" }, { "item_id": "N28", "question_type": "Long-term residual disability", "question": "Are individual recovery/disability assessments and long-term follow-up in the older-adult cases sufficiently verified?", "needed": "Original withdrawal/follow-up, neurological/gait assessments, alternative causes, and long-term denominators", "role": "Required", "role_reason": "Needed to avoid converting cases with no significant improvement 2 years after withdrawal into a probability of permanent damage or inability to recover in everyone.", "application_exception": "No significant improvement is not equivalent to confirmed complete permanent damage, a quantitative incidence rate, or recovery outcomes under other exposures.", "criterion": "Compare the scope of verification of original neurological/gait assessments, alternative causes, individual follow-up, and completeness of recovery. A summary stating that there was no significant improvement even 2 years after withdrawal is not treated as verification of a complete long-term assessment or a probability of permanent damage.", "basis": "H02: M19 §19.2 design-specific harm questions; details of temporal relationships are internally designed / H04: M19 §19.1.2–19.2.4; internal application / H08: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid converting cases with no significant improvement 2 years after withdrawal into a probability of permanent damage or inability to recover in everyone. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review recovery speed/completeness and limitations of follow-up and alternative-cause assessment.", "current_reports": [ "S24" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The 3 older-adult cases were reported to show no significant improvement in neuropathy or gait even 2 years after withdrawal. The original weight is a warning of possible persistent harm and explicitly states that a probability of permanent damage cannot be calculated. Verification of complete individual assessments/follow-up data beyond the abstract is insufficient.", "condition_status": "Partly verified", "status_reason": "The course is reported, but follow-up, denominator, and assessment data to establish individual probabilities of permanent damage/recovery are absent.", "missingness": "Individual long-term function, follow-up, causes, and risk denominators.", "uncertainty": "Individual long-term function, follow-up, causes, and risk denominators. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original withdrawal/follow-up, neurological/gait assessments, alternative causes, and long-term denominators" }, { "item_id": "N29", "question_type": "Unacquired candidates", "question": "Are the original results of candidates concerning recovery, absence of neuropathy, and high doses verified?", "needed": "S26/S27/S28 original abstracts/full texts and case/results tables", "role": "Required", "role_reason": "Needed to avoid using titles of inaccessible sources as confirmed positive/negative findings or quantitative contrary evidence.", "application_exception": "Do not convert S26/S27/S28 historical metadata/access failures into failures during this task, an effect of 0, or complete case tables.", "criterion": "Use only the actually verified scope of original results/populations, doses, durations, and confirmation; leave title/metadata candidates unverified.", "basis": "C03: M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed / C09: M04 §4.5, §4.6.3; limitations of the current material conversion follow the user’s scope and internal design / H07: M04 §4.6.1–4.6.2; adaptation for harm materials is internally designed. Rationale for application to this case: needed to avoid using titles of inaccessible sources as confirmed positive/negative findings or quantitative contrary evidence. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare candidate identity/access scope with the feasibility of extracting actual original results.", "current_reports": [ "S26", "S27", "S28" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The recovery case S26, the title concerning absence of neuropathy during homocystinuria treatment S27, and pyridoxine abuse S28 are retained as candidates whose original full texts/complete abstracts were not acquired. Quantitative values, safety, and causality were not filled in from titles/metadata alone, and the captcha/fetch failures at that time are not relabeled as failures during this task.", "condition_status": "Unverified", "status_reason": "The retained archived summaries lack sufficient abstracts/full texts to verify original clinical results, exposure, and denominators.", "missingness": "Actual original results, exposure/denominators, and diagnosis/follow-up for each candidate.", "uncertainty": "Actual original results, exposure/denominators, and diagnosis/follow-up for each candidate. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "S26/S27/S28 original abstracts/full texts and case/results tables" }, { "item_id": "N30", "question_type": "Adjacent treatment evidence", "question": "Can original observations for this harm endpoint be traced in copies of the same Levin paper?", "needed": "Tables of actual harm events, baseline status/exposure, and denominators/durations in that paper", "role": "Required", "role_reason": "Needed to avoid borrowing values from treatment evidence for pre-existing diabetic neuropathy and figures from the adjacent manuscript for this new harm table.", "application_exception": "S01/S02 are bibliographic/author copies with the same DOI/PMID, but the 6 evidence entries in source contain no detailed rows for those harm events.", "criterion": "Indicate the same-paper/copy relationship and do not fill in harm events, denominators, or doses/durations that are not currently retained.", "basis": "C01: M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed / C02: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application / C03: M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid borrowing values from treatment evidence for pre-existing diabetic neuropathy and figures from the adjacent manuscript for this new harm table. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare the copy/abstract relationship and the scope for direct extraction of these new/worsened clinical events.", "current_reports": [ "S01", "S02" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "S01/S02 refer to The influence of pyridoxine in diabetic peripheral neuropathy with the same DOI 10.2337/diacare.4.6.606 and PMID 6751736. The original citation records abstract/author-copy access locations, but the 6 evidence entries in the current source lack a detailed array of this paper’s harm events, denominators, and exposures. Figures from another efficacy manuscript were not borrowed.", "condition_status": "Unverified", "status_reason": "Only the same-bibliography relationship is verified; the original observations/denominators for this clinical harm endpoint cannot be established from the currently archived summaries.", "missingness": "Actual original values for this paper’s harm events, exposure/baseline status, denominators, and durations.", "uncertainty": "Actual original values for this paper’s harm events, exposure/baseline status, denominators, and durations. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Tables of actual harm events, baseline status/exposure, and denominators/durations in that paper" }, { "item_id": "N31", "question_type": "Roles of official documents", "question": "Were official assessments and re-citations excluded from counts of new independent human trials?", "needed": "Citation lineage in the original official documents, underlying reports, and native family/linked-source lists", "role": "Required", "role_reason": "Needed to avoid inflating counts of TGA/NIH/EFSA documents and re-citations of existing reports/experiments into independent replications.", "application_exception": "The authority of an official document does not substitute for individual events, access to original sources, or risk rates.", "criterion": "Link each official document’s background/regulatory/re-citation role to the native evidence families, without issuing an independent count of human studies or participants.", "basis": "C02: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application / H07: M04 §4.6.1–4.6.2; adaptation for harm materials is internally designed / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid inflating counts of TGA/NIH/EFSA documents and re-citations of existing reports/experiments into independent replications. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Trace re-citations/reanalyses of original experiments/reports and the roles of official documents.", "current_reports": [ "S01", "S02", "S11", "S12", "S13", "S14", "S20", "S21", "S22" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The original evidence distinguishes 6 families: Berger/Lareb/TGA/Visser/Kulkantrakorn/Court. EFSA cites Berger and Lareb again; NIH provides official background, and TGA provides selected-report/regulatory documents. S01/S02 copies of the same paper and official documents are not added together as independent trials.", "condition_status": "Met", "status_reason": "The condition of preserving the roles of documents/copies and report families was verified. The 6 families were not declared to be 6 independent clinical trials or a count of confirmed events.", "missingness": "Complete independence/overlap correspondence of individual original materials remains separately unverified.", "uncertainty": "Complete independence/overlap correspondence of individual original materials remains separately unverified. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Citation lineage in the original official documents, underlying reports, and native family/linked-source lists" }, { "item_id": "N32", "question_type": "Overall comparative risk", "question": "Are comparative risk, CI, and background risk applicable to all users verified?", "needed": "Actual exposed/unexposed, event/denominator, follow-up, RR/RD/CI, and background-risk data", "role": "Required", "role_reason": "Needed to avoid combining high-dose causality, cases/reports, and an HR from a special population into a single overall risk rate.", "application_exception": "Do not newly calculate a common RR/RD/NNH from case counts, OR, HR, and nutritional/sales criteria.", "criterion": "Retain the scope of verification of comparative estimates for the same vitamer/formulation, population, event, comparator, duration, and denominator/CI.", "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is internally designed / E05: M15 §15.3.1–15.3.3; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Rationale for application to this case: needed to avoid combining high-dose causality, cases/reports, and an HR from a special population into a single overall risk rate. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review the applicability of estimates, uncertainty, and absolute risk by population/formulation/duration.", "current_reports": [ "S20", "S21", "S22", "S23", "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The original assessment supports causality for high-dose pyridoxine but states that the risk rate among all users is unverified. Spontaneous reports lack an exposed-person denominator, and the TB HR/CIAP OR have separate contexts. No overall RR/RD/incidence, CI, NNH, or pooled estimate is calculated.", "condition_status": "Unverified", "status_reason": "There are no data establishing comparisons, denominators/durations, and risk estimates for all users addressing the same question.", "missingness": "Vitamer, formulation/population, event/comparator, denominator, and duration/CI.", "uncertainty": "Vitamer, formulation/population, event/comparator, denominator, and duration/CI. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Actual exposed/unexposed, event/denominator, follow-up, RR/RD/CI, and background-risk data" }, { "item_id": "N33", "question_type": "Vulnerable groups and long-term applicability", "question": "Are form-specific long-term risks in vulnerable groups and pre-existing neuropathy verified?", "needed": "Population-specific formulation, baseline status, exposure, long-term event/follow-up, and treatment-context data", "role": "Required", "role_reason": "Needed to avoid extending adult high-dose/report signals to individual safety/risk rates in children, pregnancy, or kidney disease.", "application_exception": "Kidney disease with low B6 markers or deficiency/metabolic disease requiring treatment does not constitute evidence of high-dose safety.", "criterion": "Check actual exposure/long-term event data and applicability limitations for kidney/liver function, pregnancy/lactation, children, and pre-existing neuropathy.", "basis": "C04: M03 §3.2.1; detailed population criteria are internally designed / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are internally designed / H08: M19 §19.1.2–19.2.4; internal application. Reason for application to this case: Needed to avoid extending adult high-dose evidence/reporting signals to individual safety/risk rates in children, pregnancy, or renal disease. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review special populations/treatment contexts and the applicability of existing evidence.", "current_reports": [ "S13", "S14", "S24", "S26", "S27" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Form-specific toxicity incidence/individual safe doses have not been verified in renal or hepatic impairment, pregnancy/lactation, children, or pre-existing neuropathy. Low B6 indicators in renal disease are not converted into high-dose safety, and contexts requiring a separate treatment benefit–risk assessment are preserved.", "condition_status": "Unverified", "status_reason": "The manuscript explicitly identifies gaps in actual population-specific incidence/doses and long-term evidence.", "missingness": "Actual formulations, exposure/denominators, and baseline/long-term events by population.", "uncertainty": "Actual formulations, exposure/denominators, and baseline/long-term events by population. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Population-specific formulation, baseline status, exposure, long-term event/follow-up, and treatment-context data" }, { "item_id": "N34", "question_type": "Minimum risk and cumulative exposure", "question": "Are the minimum risk dose/duration, individual no-risk boundary, and cumulative exposure established?", "needed": "Individual measured amounts/doses, duration/adherence, events, and comparison/denominator data", "role": "Required", "role_reason": "Needed to avoid turning unverified daily dose × duration into a new cumulative exposure or no-risk threshold.", "application_exception": "The dose–onset relationship at high doses and signals from low-dose reports represent different levels of evidence.", "criterion": "Do not present a threshold/cumulative exposure unless individual actual daily doses, duration/adherence, clinical events, and adequate risk comparisons have been verified.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation for tests are internally designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is internally designed / H02: M19 §19.2 on design-specific harm questions; details of temporal relationships are internally designed / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid turning unverified daily dose × duration into a new cumulative exposure or no-risk threshold. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Review the actual links between dose, duration, cumulative exposure, and onset/background risk.", "current_reports": [ "S14", "S20", "S21", "S22" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "An established minimum risk dose/duration and individual no-risk boundary have not been verified. Individual actual daily doses, duration, and adherence were insufficiently documented, so cumulative intake was not calculated in the manuscript either. This table creates no new conversions or minimum safety/risk thresholds.", "condition_status": "Unverified", "status_reason": "The actual components and comparative risk data needed to establish a threshold or cumulative exposure are unavailable.", "missingness": "Actual daily doses, duration/adherence, events/denominators, and risk comparisons.", "uncertainty": "Actual daily doses, duration/adherence, events/denominators, and risk comparisons. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Individual measured amounts/doses, duration/adherence, events, and comparison/denominator data" }, { "item_id": "N35", "question_type": "Nutritional upper intake levels", "question": "Have the jurisdictions/purposes of the FNB/EFSA upper intake levels been distinguished from clinical toxicity thresholds?", "needed": "Preserved FNB/EFSA editions, populations/risk assessments, and basis for UL derivation", "role": "Supporting", "role_reason": "Needed to avoid turning a nutritional upper intake level into an individual therapeutic dose recommendation/no-risk guarantee.", "application_exception": "The US 100 mg/day and EFSA 12 mg/day are not clinical comparative values obtained from the same harm study.", "criterion": "State the jurisdictions/methods, populations, and nutritional purposes of the preserved editions, and do not repurpose them as therapeutic doses, clinical thresholds, or no-risk guarantees.", "basis": "C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / H08: M19 §19.1.2–19.2.4; internal application / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid turning a nutritional upper intake level into an individual therapeutic dose recommendation/no-risk guarantee. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare jurisdictions/purposes, editions/populations, and the roles of clinical risk evidence.", "current_reports": [ "S13", "S14" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The preserved FNB adult UL is 100 mg/day, and the EFSA adult UL is 12 mg/day; these also apply to pregnant/lactating adults. The jurisdictions and assessment methods differ, and the values are not therapeutic dose recommendations, clinical toxicity thresholds, or guarantees of no risk below them. The latest official regulations were not looked up in this review.", "condition_status": "Met", "status_reason": "The preserved upper intake values and the condition for distinguishing jurisdictions/purposes were verified. This was not an assessment of new regulations or individual safety.", "missingness": "The latest official editions/regulatory updates were not looked up in this review.", "uncertainty": "The latest official editions/regulatory updates were not looked up in this review. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Preserved FNB/EFSA editions, populations/risk assessments, and basis for UL derivation" }, { "item_id": "N36", "question_type": "Label warning rules", "question": "Have TGA label warnings been distinguished from biological risk boundaries?", "needed": "Preserved TGA label warning sections, transition/application dates, and products covered", "role": "Supporting", "role_reason": "Needed to avoid mistaking a labeling criterion for the point at which risk begins/an individual safety boundary.", "application_exception": ">10 mg/day and the 2023-03-01 transition deadline are administrative events under the rules preserved as of 2026-09-15.", "criterion": "Specify the labeling purpose, jurisdiction, application reference date/transition date, and do not use them as clinical risk thresholds.", "basis": "C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid mistaking a labeling criterion for the point at which risk begins/an individual safety boundary. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Distinguish the roles and dates of administrative labeling and clinical risk evidence.", "current_reports": [ "S11" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The manuscript records Australia's label warning for supplemental medicines providing daily B6 >10 mg and the 2023-03-01 transition deadline. These are preserved as labeling rules in force on 2026-09-15 and are not turned into a biological boundary at which risk begins or a new regulatory lookup in this review.", "condition_status": "Met", "status_reason": "The boundaries of the original labeling/date records and the prohibition on repurposing them as clinical thresholds were verified.", "missingness": "Verification of the latest labeling/regulations was not attempted in this review.", "uncertainty": "Verification of the latest labeling/regulations was not attempted in this review. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Preserved TGA label warning sections, transition/application dates, and products covered" }, { "item_id": "N37", "question_type": "Future sales classification", "question": "Has the future TGA sales classification been distinguished from current prescription/labeling rules?", "needed": "Preserved TGA sections on sales classification/effective dates and products covered", "role": "Supporting", "role_reason": "Needed to avoid retroactively treating regulations scheduled for 2027 as current rules/clinically safe doses in 2026.", "application_exception": "Pharmacist control at >50–≤200 mg/day and prescription control at >200 mg/day are neither nutritional ULs nor equivalent risk categories.", "criterion": "At the reference date 2026-09-15, separately state the scheduled 2027-06-01 date, dose ranges, and sales purposes.", "basis": "C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid retroactively treating regulations scheduled for 2027 as current rules/clinically safe doses in 2026. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare current/future application dates and the purposes of sales, labeling, and nutritional criteria.", "current_reports": [ "S12" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Australia's transition to pharmacist control for products providing more than 50 mg/day–up to and including 200 mg/day is scheduled for 2027-06-01 and was a future regulation as of 2026-09-15. It is distinguished from prescription control above 200 mg/day. Labeling/sales/nutritional ULs are different rules and are not clinical toxicity boundaries.", "condition_status": "Met", "status_reason": "The purposes and date attribution of the original scheduled/current rules were distinguished. Their implementation/latest status was not looked up in this review.", "missingness": "Verification of the latest sales regulations was not attempted in this review.", "uncertainty": "Verification of the latest sales regulations was not attempted in this review. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Preserved TGA sections on sales classification/effective dates and products covered" }, { "item_id": "N38", "question_type": "Funding and roles", "question": "Is the actual scope of verification of funding, product supply, and conflicts of interest known for each report?", "needed": "Original funding/COI, product supply, and design/analysis/reporting role declarations", "role": "Required", "role_reason": "Needed to avoid filling in indexed grants or unverified information as no funding/no industry involvement/independence.", "application_exception": "The 2018 no-funding statement, unverified 2025 funding, and NIH/Wellcome indexed support are not at the same level of verification.", "criterion": "Distinguish each report's actual declarations/indexing from unverified funding, supply/roles, and conflicts of interest.", "basis": "C10: Chamgap's own conditions for independence and attribution. The official methodology sections used in this pilot do not endorse all of these detailed items. Reason for application to this case: Needed to avoid filling in indexed grants or unverified information as no funding/no industry involvement/independence. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare each report's support/declarations with the scope of verification of actual research/product roles.", "current_reports": [ "S20", "S21", "S22", "S23", "S24", "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "Lareb 2018 includes a statement of no funding for preparation, while the complete funding for 2025 is unverified. For Visser, only EFSA's mention of foundation support is available, and verification of the original roles is insufficient. Court's PubMed record indexes NIH/NIAID·Wellcome support, but the complete sponsor roles/product supply are unverified. Funding for Berger and the elderly cases is also unverified.", "condition_status": "Partly verified", "status_reason": "Some declarations/indexing and official activities are documented, but material establishing the complete funding/supply/roles for each report is unavailable.", "missingness": "Original funding/COI, product supply, and research/reporting roles.", "uncertainty": "Original funding/COI, product supply, and research/reporting roles. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original funding/COI, product supply, and design/analysis/reporting role declarations" }, { "item_id": "N39", "question_type": "Advance plans and search scope", "question": "Is the actual scope of verification of registration, plans, and corrections/retractions sufficiently established?", "needed": "Registration, protocol/SAP, changes, and correction/retraction search logs/original publication records", "role": "Required", "role_reason": "Needed to avoid extending unverified information/the recorded search scope into absence of preregistration, absence of corrections, or integrity of the entire literature.", "application_exception": "An empty registry_id is not proof of no registration, and the search_record wording is not evidence that the search logs were actually read in this review.", "criterion": "Verify actual registration/protocols, data collection/SAP, changes, correction/retraction searches, and their scope, and leave unavailable original logs unverified.", "basis": "C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design / E06: M08 Table 8.2.a, M04 §4.6.3; internal application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Reason for application to this case: Needed to avoid extending unverified information/the recorded search scope into absence of preregistration, absence of corrections, or integrity of the entire literature. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare advance plans/changes and original reports with the scope of searches/access.", "current_reports": [ "S20", "S21", "S22", "S23", "S24", "S25" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The registry_id values in the 15 citations are empty, and the manuscript limits registration/correction/retraction searches to the recorded scope. The manuscript states that detailed search/access/selection records are in the delivery package, but the ZIP/separate logs referred to there were not read in the review described in that record. No new determination is made that registration is absent or that the entire literature has integrity.", "condition_status": "Unverified", "status_reason": "The currently preserved archived summaries alone cannot establish the full scope of plans/registration or actual detailed search and change/correction/retraction verification.", "missingness": "Original registration/plans, changes, and correction/retraction search/publication records.", "uncertainty": "Original registration/plans, changes, and correction/retraction search/publication records. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Registration, protocol/SAP, changes, and correction/retraction search logs/original publication records" }, { "item_id": "N40", "question_type": "Distinguishing reading and dates", "question": "Have the current summary reading, historical access to originals, and review/access dates been distinguished?", "needed": "Original bytes of the currently preserved archived summaries, citation access locations/identities, and access-date records", "role": "Required", "role_reason": "Needed to avoid upgrading the reading of preserved archived summaries to reading original full-text papers in this review.", "application_exception": "Do not reuse citations' historical access_level/location or the global verified_date as current full-text access/individual access dates.", "criterion": "Record the actual local summary locations/SHA separately from external access not attempted/materials unread, historical material types/access, and empty per-report access dates.", "basis": "C03: M04 §4.5–4.6 principles for material collection/selection; separation of access and reading and the hyperlink contract are internally designed / C09: M04 §4.5, §4.6.3; limitations on the current material conversion reflect the user's scope and internal design. Reason for application to this case: Needed to avoid upgrading the reading of preserved archived summaries to reading original full-text papers in this review. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare material types, original locations, historical/current reading events, and dates.", "current_reports": [ "S01", "S02", "S11", "S12", "S13", "S14", "S20", "S21", "S22", "S23", "S24", "S25", "S26", "S27", "S28" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The KO/EN text, 6 evidence entries/15 bibliographic entries, assessments, and metadata in the current source were actually read. Access to all external originals/official pages, registrations, and old separate files was not attempted, and these were not acquired or read in this review. Historical access_level/location remain unchanged; individual access-date keys are absent, leaving empty values, and the original verified_date 2026-09-15 is distinguished solely as the review date.", "condition_status": "Met", "status_reason": "The narrow record condition distinguishing actual local reading in this review from historical/external unread materials and dates was verified.", "missingness": "Actual verification of external full texts/underlying data was not performed in this review.", "uncertainty": "Actual verification of external full texts/underlying data was not performed in this review. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original bytes of the currently preserved archived summaries, citation access locations/identities, and access-date records" }, { "item_id": "N41", "question_type": "Personal treatment boundary", "question": "Has the original safety warning been kept from becoming personal treatment/discontinuation instructions?", "needed": "Original safety warning and personal application/treatment boundary", "role": "Required", "role_reason": "Needed to avoid turning harm information into instructions to stop/replace prescriptions or take individual doses.", "application_exception": "The blue record statuses in the review table and the original warning are not individual safety guarantees or self-treatment instructions.", "criterion": "Preserve the original safety information and assessment limitations, and do not newly assign individual recommended doses or instructions for self-directed dose escalation/prescription discontinuation.", "basis": "C01: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed / H09: Chamgap's own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to this case: Needed to avoid turning harm information into instructions to stop/replace prescriptions or take individual doses. No formal causality/harm grading assessment was performed.", "condition_origin": "The development conditions, designed after this case had already been read, were actually frozen in advance. This was not automated machine copying, blinding/clinical preregistration, or methodological certification.", "proposed_research": "Compare the boundary between public informational statements and personal treatment instructions with the actual original values.", "current_reports": [ "S11", "S12", "S13", "S14" ], "existence": "Limited to currently preserved content, structure/bibliographic information, and explicitly stated historical unverified matters.", "acquired_read": "Summary reading: the specified original locations in the currently archived source summaries were actually read. Access to external material types was not attempted, and they were not read in this review.", "observation": "The original document explicitly states that it does not provide personal treatment/dosing instructions. For new tingling, burning, reduced sensation, or balance problems, it advises assessment of all products/other causes and preserves the original wording against unnecessary self-directed dose escalation or arbitrary discontinuation/replacement of prescribed treatment. This table creates no new clinical instructions.", "condition_status": "Met", "status_reason": "Only the boundaries of the preserved information were verified; individual doses, discontinuation, or treatment were not assessed.", "missingness": "Individual causes/doses and treatment benefit–risk are not new conclusions of this table.", "uncertainty": "Individual causes/doses and treatment benefit–risk are not new conclusions of this table. This status concerns a narrow scope of record/material verification and does not newly assess clinical causality, occurrence probability, or individual safety.", "review_date": "2026-10-05", "reading_status": "Original text unread · Archived summary read", "additional_material": "Original safety warning and personal application/treatment boundary" } ], "reports": [ { "report_id": "S01", "title": "The influence of pyridoxine in diabetic peripheral neuropathy", "url": "https://pubmed.ncbi.nlm.nih.gov/6751736/", "report_type": "Original-paper abstract/bibliographic record (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at the time of preservation: This is the abstract bibliographic record for the Levin paper, DOI 10.2337/diacare.4.6.606·PMID 6751736. It is the same paper as S02, and the current 6 evidence entries do not preserve this paper's details on new/worsened harm events, denominators, doses, or duration. Values from the adjacent efficacy assessment are not borrowed.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed original-paper abstract and bibliographic record", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract. Historical location in the reference bibliography: Abstract; Diabetes Care 4(6):606-609 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S01-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/6751736/", "parent_url": null }, { "material_type": "Separate original-paper PDF full text (exact URL/actual historical access unverified)", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract; Diabetes Care 4(6):606-609 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S01-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/6751736/" } ] }, { "report_id": "S02", "title": "Levin 1981: author-deposited full-text rendering", "url": "https://www.researchgate.net/publication/16446742_The_Influence_of_Pyridoxine_in_Diabetic_Peripheral_Neuropathy", "report_type": "ResearchGate author-deposited full-text HTML (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at the time of preservation: The original access_level is author_deposited_full_text_html, and historical locations in Subjects/Methods·Results/Symptoms·Discussion are recorded. What was read in this review was the citation and the related archived source summary; this external copy/its numerical results were not newly read.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "ResearchGate author-deposited full-text HTML", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: author_deposited_full_text_html. Historical location in the reference bibliography: pp606-607 Subjects and Methods; Study protocol; p607 Results/Symptoms; p608 Discussion. Web text lines199-263,323-365,395-437,615-655 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S02-M1", "url": "https://www.researchgate.net/publication/16446742_The_Influence_of_Pyridoxine_in_Diabetic_Peripheral_Neuropathy", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.researchgate.net/publication/16446742_The_Influence_of_Pyridoxine_in_Diabetic_Peripheral_Neuropathy" } ] }, { "report_id": "S11", "title": "Peripheral neuropathy with supplementary vitamin B6 (pyridoxine)", "url": "https://www.tga.gov.au/news/safety-updates/peripheral-neuropathy-supplementary-vitamin-b6-pyridoxine", "report_type": "TGA official safety web document (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": "F-TGA", "independent_replication": null, "observed_result": "Record at the time of preservation: Through 2022-08-05, 32 reports were selected; 21 involved 50 mg/day or less, and 9 involved multiple products, so the categories may overlap. The daily B6 >10 mg label warning and 2023-03-01 transition are administrative rules. Incidence among exposed users/minimum risk doses are not calculated.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "TGA official safety web full text", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: official_full_html. Historical location in the reference bibliography: Background and review of 32 reports through 2022-08-05; listed-medicine label threshold >10 mg/day; transition 2023-03-01; product forms Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S11-M1", "url": "https://www.tga.gov.au/news/safety-updates/peripheral-neuropathy-supplementary-vitamin-b6-pyridoxine", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.tga.gov.au/news/safety-updates/peripheral-neuropathy-supplementary-vitamin-b6-pyridoxine" } ] }, { "report_id": "S12", "title": "Medicines containing vitamin B6 (pyridoxine, pyridoxal or pyridoxamine)", "url": "https://www.tga.gov.au/news/safety-updates/medicines-containing-vitamin-b6-pyridoxine-pyridoxal-or-pyridoxamine", "report_type": "TGA official medicine safety web document (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": "F-TGA", "independent_replication": null, "observed_result": "Record at the time of preservation: The transition to pharmacist control above 50 mg/day–up to and including 200 mg/day is scheduled for 2027-06-01 and was a future regulation at the original reference date 2026-09-15. It is distinguished from prescription control above 200 mg/day. The original location records published2026-02-19/updated2026-04-07; these are not actual access dates.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "TGA official safety/sales classification web full text", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: official_full_html. Historical location in the reference bibliography: Summary and What health professionals should do, lines195-210; published2026-02-19, updated2026-04-07 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S12-M1", "url": "https://www.tga.gov.au/news/safety-updates/medicines-containing-vitamin-b6-pyridoxine-pyridoxal-or-pyridoxamine", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.tga.gov.au/news/safety-updates/medicines-containing-vitamin-b6-pyridoxine-pyridoxal-or-pyridoxamine" } ] }, { "report_id": "S13", "title": "Vitamin B6: Fact Sheet for Health Professionals", "url": "https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/", "report_type": "NIH ODS official professional web commentary (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at the time of preservation: The manuscript distinguishes the FNB adult UL of 100 mg/day from the EFSA 12 mg/day value by jurisdiction/purpose. It uses general background on impaired renal function/interactions and harm, and does not turn nutritional upper intake levels into therapeutic dose recommendations, clinical thresholds, or no-risk guarantees.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "NIH ODS official professional web full text", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: official_full_html. Historical location in the reference bibliography: Introduction; Individuals with Impaired Renal Function; Health Risks; Table3; Interactions with Medications Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S13-M1", "url": "https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/" } ] }, { "report_id": "S14", "title": "Scientific opinion on the tolerable upper intake level for vitamin B6", "url": "https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2023.8006", "report_type": "EFSA official risk assessment HTML (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at the time of preservation: EFSA cites the Berger individual-participant table and the Lareb reporting series again. The discrepancy with the Berger abstract in the clinical-symptom numerator and the participants with test changes alone are preserved. The adult UL of 12 mg/day is a nutritional risk assessment criterion, not a no-risk boundary for all low doses or a clinical toxicity threshold.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "EFSA official risk assessment full-text HTML and Appendix tables", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: official_full_html. Historical location in the reference bibliography: Sections 3.6.1 and 3.6.1.1; human evidence and nutrivigilance; uncertainty; Appendix D.1.1 Berger table; derivation of adult UL Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S14-M1", "url": "https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2023.8006", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2023.8006" } ] }, { "report_id": "S20", "title": "Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity", "url": "https://pubmed.ncbi.nlm.nih.gov/1620347/", "report_type": "Original-paper abstract (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": "F-BERGER", "independent_replication": null, "observed_result": "Record at the time of preservation: This was prospective, uncontrolled exposure of 5 volunteers to pyridoxine at 1 or 3 g/day. Earlier onset at the higher dose and worsening for 2–3 weeks after withdrawal were reported, but the abstract/EFSA clinical numerators do not agree, so neither 5/5 nor population incidence is claimed.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed original-paper abstract and bibliographic record", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract. Historical location in the reference bibliography: Abstract; Neurology 1992;42(7):1367-1370 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S20-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/1620347/", "parent_url": null }, { "material_type": "Separate original-paper PDF full text (exact URL/actual historical access unverified)", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract; Neurology 1992;42(7):1367-1370 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S20-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/1620347/" } ] }, { "report_id": "S21", "title": "Vitamin B6 in Health Supplements and Neuropathy: Case Series Assessment of Spontaneously Reported Cases", "url": "https://link.springer.com/article/10.1007/s40264-018-0664-0", "report_type": "Publisher abstract and funding/COI declarations (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": "F-LAREB", "independent_replication": null, "observed_result": "Record at the time of preservation: The 2018 reports, totaling 90, overlap with the subsequent 224 reports in the same Lareb reporting series. The 1.4–100 mg range is the content per tablet, not actual total daily intake/a threshold. A declaration of no funding for preparation was recorded, but gaps in the exposed-user denominator, clinical confirmation, and duration of the reports remain.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Publisher original-paper abstract and Funding/COI declaration HTML", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract_and_declarations. Historical location in the reference bibliography: Abstract Methods/Results/Conclusion; declarations Funding and Conflicts; Drug Safety 2018;41:859-869 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S21-M1", "url": "https://link.springer.com/article/10.1007/s40264-018-0664-0", "parent_url": null }, { "material_type": "Separate original-paper PDF full text (exact URL/actual historical access unverified)", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract Methods/Results/Conclusion; declarations Funding and Conflicts; Drug Safety 2018;41:859-869 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S21-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://link.springer.com/article/10.1007/s40264-018-0664-0" } ] }, { "report_id": "S22", "title": "Impact of Regulatory Action on Dose Maximalization for Vitamin B6 Dietary Supplements on the Reporting Pattern for Neuropathy", "url": "https://onlinelibrary.wiley.com/doi/10.1002/pds.70108", "report_type": "Publisher original-paper full-text HTML (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": "F-LAREB", "independent_replication": null, "observed_result": "Record at the time of preservation: For the reporting collection window 2007-08–2023-12-31, this is an analysis of 224 reports, overlapping with the earlier 2018 series of 90 reports/EFSA interim counts. Actual daily doses/duration, clinical confirmation, and the exposed-user denominator are insufficient, so incidence is not calculated. The complete funding declaration is unverified.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Publisher original-paper full-text HTML", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_full_html. Historical location in the reference bibliography: Abstract; Methods case selection; Results; Discussion paragraphs on earlier 90 reports, no exposed denominator, unknown duration; COI; 2025;34:e70108 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S22-M1", "url": "https://onlinelibrary.wiley.com/doi/10.1002/pds.70108", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://onlinelibrary.wiley.com/doi/10.1002/pds.70108" } ] }, { "report_id": "S23", "title": "Chronic idiopathic axonal polyneuropathy and vitamin B6: a controlled population-based study", "url": "https://onlinelibrary.wiley.com/doi/10.1111/jns5.12063", "report_type": "Publisher original-paper abstract (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": "F-VISSER", "independent_replication": null, "observed_result": "Record at the time of preservation: Among 381 people with pre-existing CIAP and 140 controls, the median blood concentrations were 99 versus 109 nmol/L, with P=0.58. Supplement use was 31% versus 22%, OR 1.7 (95% CI 1.0–2.7; P=0.032), and the authors interpreted a causal relationship as unlikely. Reverse causation/selection are retained, and these findings are not used as new-onset incidence rates or a no-risk guarantee.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Publisher original-paper abstract and bibliographic HTML", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract. Historical location in the reference bibliography: Abstract; J Peripheral Nervous System 2014;19:136-144 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S23-M1", "url": "https://onlinelibrary.wiley.com/doi/10.1111/jns5.12063", "parent_url": null }, { "material_type": "Separate original-paper PDF full text (exact URL/actual historical access unverified)", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract; J Peripheral Nervous System 2014;19:136-144 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S23-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://onlinelibrary.wiley.com/doi/10.1111/jns5.12063" } ] }, { "report_id": "S24", "title": "Pyridoxine-induced sensory ataxic neuronopathy and neuropathy: revisited", "url": "https://pubmed.ncbi.nlm.nih.gov/25056196/", "report_type": "Original-paper abstract (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": "F-KULKANTRAKORN", "independent_replication": null, "observed_result": "Record at the time of preservation: Aged 80·83·83, the 3 people had cases of sensory ataxic neuropathy/gait impairment. They took B1/B6/B12 combination tablets providing pyridoxine 600 mg/day for 3–10 years, with no significant improvement even 2 years after withdrawal. No single-ingredient-product incidence or probability of permanent damage is presented.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed original-paper abstract and bibliographic record", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract. Historical location in the reference bibliography: Abstract; Neurol Sci 2014;35(11):1827-1830 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S24-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/25056196/", "parent_url": null }, { "material_type": "Separate original-paper PDF full text (exact URL/actual historical access unverified)", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract; Neurol Sci 2014;35(11):1827-1830 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S24-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/25056196/" } ] }, { "report_id": "S25", "title": "Neuropsychiatric toxicity and cycloserine concentrations during treatment for multidrug-resistant tuberculosis", "url": "https://pubmed.ncbi.nlm.nih.gov/33684562/", "report_type": "Original-paper abstract, declarations/support indexing (historical access)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": "F-COURT", "independent_replication": null, "observed_result": "Record at the time of preservation: Recruitment was 144 people, with neuropathy in 50 (35% in the original). For pyridoxine 200 versus 150 mg/day, an adjusted HR of 2.79, P=0.01, was reported for mixed new/worsened events. Arm-specific denominators/events, CI, exact follow-up, and separate counts are unverified, and HIV/TB, concomitant treatment, and prescribing confounding remain. The composite neuropsychiatric AE person-month incidence is not repurposed. NIH/NIAID·Wellcome grants are limited to the indexing record.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed abstract, figure captions, and COI/Grants indexing", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: primary_abstract_declarations_funding. Historical location in the reference bibliography: Abstract Methods/Results/Conclusions; figure captions; COI; Grants and funding; IJID 2021;105:688-694 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S25-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/33684562/", "parent_url": null }, { "material_type": "Separate original-paper PDF full text (exact URL/actual historical access unverified)", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Abstract Methods/Results/Conclusions; figure captions; COI; Grants and funding; IJID 2021;105:688-694 Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S25-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/33684562/" } ] }, { "report_id": "S26", "title": "Regressive pyridoxine-induced sensory neuronopathy in a patient with homocystinuria", "url": "https://pubmed.ncbi.nlm.nih.gov/29954767/", "report_type": "Candidate original-paper metadata/search snippet (historical; original results not acquired)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at the time of preservation: The title/DOI/PMID of a recovery case were identified. An empty original PubMed body, PMC6040505 captcha, and BMJ fetch failure are recorded in the historical location; the complete abstract/full text was not acquired, so it was not used for quantitative values/a recovery guarantee. This is not upgraded to a failure in this review or evidence of clinical absence in unread material.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed bibliographic/candidate metadata route", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: metadata_search_snippet_primary_text_unavailable. Historical location in the reference bibliography: Search metadata; PubMed empty body; PMC6040505 captcha; BMJ fetch failure Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S26-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/29954767/", "parent_url": null }, { "material_type": "Separate BMJ/PMC original-paper full text (exact URL/actual historical access unverified)", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Search metadata; PubMed empty body; PMC6040505 captcha; BMJ fetch failure Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S26-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/29954767/" } ] }, { "report_id": "S27", "title": "No sensory neuropathy during pyridoxine treatment in homocystinuria", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC1793039/", "report_type": "PMC candidate original-paper link (historically only metadata verified/original text not acquired)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at the time of preservation: The title No sensory neuropathy during pyridoxine treatment in homocystinuria and its DOI were identified. Because of a PMC captcha/publisher fetch failure, values from the original full text/complete abstract were not used. The title is not interpreted as 0 adverse events, long-term safety, or absence of risk.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PMC original-paper HTML link (historically only metadata verified)", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Article metadata identified; PMC captcha; publisher fetch failed Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S27-M1", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC1793039/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC1793039/" } ] }, { "report_id": "S28", "title": "Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome", "url": "https://pubmed.ncbi.nlm.nih.gov/6308447/", "report_type": "Candidate original-paper metadata (historical; original text not acquired)", "existence": "This refers to archived bibliographic information and past records; current external responses have not been verified.", "acquired_read": "The relevant Korean/English summaries and bibliographic records in the archived manuscript were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at the time of preservation: The title Sensory neuropathy from pyridoxine abuse and DOI/PMID were identified. The EFSA reference and PubMed empty response/NEJM access failure are recorded in the historical location. The current source lacks details of original denominators/exact exposure, duration, and events, so these were not used as new values.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed candidate bibliographic route", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Only the extent to which the original citation records access to this physical material itself is preserved. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: metadata_primary_text_unavailable. Historical location in the reference bibliography: Reference in EFSA; PubMed empty response; NEJM access failed Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S28-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/6308447/", "parent_url": null }, { "material_type": "Separate NEJM original-paper PDF full text (exact URL/actual historical access unverified)", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-02", "qualification": "Limited to the preserved identity/access records and the required material type. External existence/public availability was not newly verified in this review. Only the relevant content, evidence, and bibliography in the currently preserved archived source summary were read. The external material concerned was not read in this review. Historical access to the included bibliography/abstract and metadata provides reference context. It is not inherited as the actual access level of a separate original text or underlying material. Historical access dates for each material are unverified. The archived manuscript review date 2026-09-15 is not the access date of this original material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Reference in EFSA; PubMed empty response; NEJM access failed Bibliographic access records are not inherited as access to a separate full text or underlying material. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S28-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/6308447/" } ] } ], "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly document the question, eligibility criteria, and reasons for changes, and distinguish intervention variants.", "review_level": "Historical reuse of methodology materials preserved in 1585: the verified original-byte/SHA copy of HTML5 and the principles. This is not new reading of the full methodology or implementation/certification of an official method." }, { "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 exclude a study solely because outcomes are unreported.", "review_level": "Historical reuse of methodology materials preserved in 1585: the verified original-byte/SHA copy of HTML5 and the principles. This is not new reading of the full methodology or implementation/certification of an official method." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Fix the outcome and effect of interest, and review randomization, deviations, missing data, measurement, and selective reporting.", "review_level": "Historical reuse of methodology materials preserved in 1585: the verified original-byte/SHA copy of HTML5 and the principles. This is not new reading of the full methodology or implementation/certification of an official method." }, { "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": "Historical reuse of methodology materials preserved in 1585: the verified original-byte/SHA copy of HTML5 and the principles. This is not new reading of the full methodology or implementation/certification of an official method." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require designs, populations, and follow-up different from those for efficacy. Case reports do not establish incidence.", "review_level": "Historical reuse of methodology materials preserved in 1585: the verified original-byte/SHA copy of HTML5 and the principles. This is not new reading of the full methodology or implementation/certification of an official method." } ], "status_dictionary": { "Met": "The relevant narrow conditions for identity/attribution, original values/boundaries, and reading records are met. This is not a new confirmation of clinical causality, efficacy, absence of risk, or external full texts.", "Partly verified": "Relevant preserved observations exist, but some aspects of actual exposure/events, denominators, methods/attribution could not be established.", "Unverified": "Not established within the archived materials and the scope verified at that time. This does not mean 0 risk, absence of research worldwide, or access failure in this review.", "Conflicting information": "Inconsistent preserved descriptions of the same clinical fact remain. Success in recording and preserving the conflict is distinguished from actual consistent verification.", "Not applicable": "Limited to material roles excluded by the question's boundaries. It is not a substitute for unverified/unread/no risk.", "Not reported": "Explicitly unreported within the actual preserved manuscript/historical verification scope. This is not extended to the entirety of full texts unread in this review.", "Inaccessible": "Limited to actual access failure in this review; the absence of external access attempts in this case is not upgraded to a past failure.", "Review incomplete": "Limited to the lack of current external comparison. It does not mean that the actually completed review of local archived summaries/individual models is incomplete." }, "study_overlap": { "state": "The 6 archived evidence families do not represent the number of independent clinical trials or a participant total. F-BERGER (S20, S14): Evidence for high-dose pyridoxine causality; not used as population incidence / F-LAREB (S21, S22, S14): Used as a safety signal; counts are not summed as mutually independent / F-TGA (S11, S12): Evidence for a possible low-dose signal and label warnings; not a biological threshold / F-VISSER (S23): Contrary/limiting evidence preserved; neither a no-risk guarantee nor a causal incidence estimate / F-KULKANTRAKORN (S24): Warning of possible persistent harm; probability of permanent damage cannot be calculated / F-COURT (S25): Contextual evidence from a dose comparison; not repurposed as a causal RR for general supplement use. Duplicate counts of the same reports and repeat citations in official documents are not summed.", "unique_trial_count": null, "unique_participant_count": null, "reason": "The 6 archived evidence families do not represent the number of independent clinical trials or a participant total. F-BERGER (S20, S14): Evidence for high-dose pyridoxine causality; not used as population incidence / F-LAREB (S21, S22, S14): Used as a safety signal; counts are not summed as mutually independent / F-TGA (S11, S12): Evidence for a possible low-dose signal and label warnings; not a biological threshold / F-VISSER (S23): Contrary/limiting evidence preserved; neither a no-risk guarantee nor a causal incidence estimate / F-KULKANTRAKORN (S24): Warning of possible persistent harm; probability of permanent damage cannot be calculated / F-COURT (S25): Contextual evidence from a dose comparison; not repurposed as a causal RR for general supplement use. Duplicate counts of the same reports and repeat citations in official documents are not summed." }, "history": [ { "date": "2026-11-02", "kind": "Public display and data separation", "view_version": "1.0", "change": "The public display and data were prepared from the existing 41 items. No new clinical search, verification-status change, or scoring was performed." } ], "safety_scope": { "question_type": "safety", "deliverable_kind": "safety_brief", "safety_only": true, "grading_status": "not_applicable_safety", "efficacy_grade": "not_applicable", "efficacy_score": "not_applicable", "efficacy_framework_applied": false, "forbid_efficacy_badge": true, "forbid_aggregate_rating": true, "warning": "Warning", "meaning": "This is a safety-only review. Item verification statuses represent the scope of verification of archived materials and question boundaries; they do not signify efficacy grades, individual safety guarantees, or occurrence probabilities." }, "reader_labels": { "independent_replication_unverified": "Independent replication is unverified." }, "language": "en", "translation_date": "2026-11-02" }