{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3097-main", "verdict_number": "3097", "title": "Vitamin B6: pyridoxine hydrochloride × Lower mean pain NRS in painful diabetic distal symmetric polyneuropathy", "view_version": "1.0", "view_created_date": "2026-11-02", "criteria_version": "CG-GAP-v3097-main-1.0", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-15", "review_scope": { "materials_read": "Retained 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, registry records or analysis plans were newly read. Historical access records are distinguished from the retained summaries read in this review. The original judgment, numbers and unverified details were preserved, with no new search, calculation or reassessment.", "date_meaning": "This is the date the retained materials were reviewed, not the date of a search for the latest clinical literature." }, "claim_context": { "population": "Adults with painful diabetic distal symmetric polyneuropathy; distinct from treatment solely to correct B6 deficiency", "intervention": "Vitamin B6: pyridoxine hydrochloride alone · Oral pyridoxine hydrochloride alone", "dose": "Unverified: no dose has been identified for an eligible mean NRS comparison. The adjacent trial’s 50 mg every 8 hours is not a dose with verified efficacy", "comparator": "A question about placebo on the same background care. Placebo composition, analgesics and rescue medication in eligible studies are unverified", "endpoint": "Between-group difference in mean pain NRS change. The preferred range for the question is 0–10; the actual eligible instrument, time point and denominator are unverified. VAS is separate", "duration": "Unverified: no eligible NRS time point has been identified. Categorical symptoms from the adjacent 4-month trial are not converted to NRS", "excluded_extensions": [ "Ordinal improvement in pain or paresthesia", "VAS, NTSS-6 and vibration perception threshold", "PLP/folate/B12 and B1/B6/B12 combinations", "Metabolism, oxidative stress, nerve conduction and blood glucose", "Treatment solely to correct deficiency", "Uncontrolled heterogeneous foot pain", "Incidence/causation of B6 harms and a safe dose for an individual" ] }, "requirements": [ { "item_id": "N01", "question_type": "Claim boundaries", "question": "Which population, intervention, comparator and pain outcome are being examined as a single question?", "needed": "The connection between the current /ko/effect and oral pyridoxine hydrochloride alone, adults with painful DSPN, placebo on the same background care and mean NRS.", "role": "Required", "role_reason": "Fixing this scope prevents categorical improvement or combination-product results from substituting for the NRS effect of monotherapy.", "application_exception": "If an actual monotherapy NRS study is verified, add its dose and duration with attribution to that study. Do not treat currently unverified dimensions as wildcards for all conditions.", "criterion": "Keep the subject of the judgment linked as recorded and fix the scope of monotherapy, diagnosis and between-group mean NRS. Leave other ingredients, conditions and scales in separate scopes.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are custom-designed / M03 §3.2.1; detailed population conditions are custom-designed / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "First screen studies that retain this question, and extract combinations, deficiency correction and other endpoints separately.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The subject of the judgment is reduction in mean pain NRS in painful diabetic distal symmetric polyneuropathy. It was read as a question comparing oral pyridoxine hydrochloride alone with placebo on the same background care.", "condition_status": "Verified", "status_reason": "The population, intervention and endpoint in the Korean and English text and facets point to the same single question. This verification does not mean that a direct NRS effect estimate was obtained.", "missingness": "There is no gap in the identity of the subject being judged, but the actual eligible dose, duration, scale and denominator remain separately unverified.", "uncertainty": "There is no gap in the identity of the subject being judged, but the actual eligible dose, duration, scale and denominator remain separately unverified.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "When revising the claim, record the manuscript, facets, reasons and identity before and after the revision." }, { "item_id": "N02", "question_type": "Ingredient and formulation", "question": "Do the actual study ingredient, route and formulation match the question about pyridoxine hydrochloride alone?", "needed": "The vitamer, salt and all active ingredients; oral route; and tablet release type, purity, batch and manufacturing origin.", "role": "Required", "role_reason": "Differences in vitamers, salts and combination composition directly affect attribution to a single ingredient.", "application_exception": "Do not fill in release type, purity or batch solely from a record that says tablets. Do not merge a PLP combination into the same intervention merely because it has the same vitamin name.", "criterion": "Distinguish oral pyridoxine hydrochloride alone from a PLP/B12/folate combination, and link only the formulation actually verified to the relevant study.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M03 §3.2.3, M08 §8.2.2–8.2.3; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Verify the sole active ingredient of the investigational product and the placebo composition, then include only comparisons of that same product in the direct question.", "current_reports": [ "S01", "S02", "S05", "S13" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The question concerns oral pyridoxine hydrochloride alone. The adjacent Levin trial used tablets, but formulation, release type, purity, batch and manufacturing origin in eligible NRS studies are unverified.", "condition_status": "Partly verified", "status_reason": "There are records of the ingredient, route and tablets in the adjacent trial, but the full identity of the product used in a direct NRS comparison has not been verified.", "missingness": "Gaps in eligible product composition, manufacturing origin, release type, purity and batch.", "uncertainty": "Gaps in eligible product composition, manufacturing origin, release type, purity and batch.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Investigational-product and placebo specifications, manufacturing documents and quality documents for each candidate." }, { "item_id": "N03", "question_type": "Participant diagnosis", "question": "Were participants selected as having painful diabetic DSPN?", "needed": "Diagnostic and selection criteria for diabetes, distal symmetric neuropathy and pain; age, baseline pain and exclusion criteria.", "role": "Required", "role_reason": "A population with symptomatic diabetes cannot automatically be treated as the same eligible population as precisely diagnosed painful DSPN.", "application_exception": "Do not conclude that the population was different because the selection criteria were not read. If separate results for a mixed population become available, review only that scope.", "criterion": "Compare the actual participant diagnoses with the fixed question; do not establish eligibility for painful DSPN solely from the wording symptomatic diabetes.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed / M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Define diabetic distal symmetric neuropathy and pain in advance, and separate results for other neuropathies and populations treated to correct deficiency.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The question concerns adults with painful DSPN. Levin included 18 patients with symptomatic diabetes, but the exact selection criteria for painful DSPN were not verified.", "condition_status": "Partly verified", "status_reason": "Information on diabetes and a symptomatic population is available, but direct eligibility in terms of pain diagnosis, selection procedures and baseline pain is unverified.", "missingness": "Gaps in the diagnostic protocol, selection based on pain and detailed baseline status.", "uncertainty": "Gaps in the diagnostic protocol, selection based on pain and detailed baseline status.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Selection and exclusion criteria and baseline-characteristics tables for Levin and McCann/Cohen." }, { "item_id": "N04", "question_type": "Deficiency and special populations", "question": "Are data available to distinguish correction of B6 deficiency from the separate questions concerning kidney disease, pregnancy and lactation?", "needed": "Assessment of baseline deficiency and participants by stratum; inclusion of participants by kidney function, pregnancy and lactation; and direct pain estimates.", "role": "Supplementary; required for extension to those populations", "role_reason": "Differences in baseline nutritional status and safety in special populations limit generalization of the NRS effect of monotherapy.", "application_exception": "Do not require studies of every special population for the narrow adult NRS question. Direct data are needed for claims extending to those populations.", "criterion": "Separate treatment solely to correct deficiency from the specified pain-efficacy question, and do not infer an analgesic effect solely from low B6 indices.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed / M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed / M19 §19.1.2–19.2.4; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Prespecify the deficiency-correction stratum, and examine effect modification by kidney function and other factors through separate estimates and interactions. Do not use this table to determine an individual’s dose.", "current_reports": [ "S13", "S14" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The manuscript distinguishes correction of B6 deficiency as a separate question. Dose and long-term safety for this pain question in kidney disease, pregnancy and lactation are unverified, and low B6 indices are not evidence of analgesic efficacy.", "condition_status": "Unverified", "status_reason": "The preserved inputs contain no direct NRS results by population stratum or information on deficiency assessment and inclusion of special populations.", "missingness": "Gaps in direct results by strata of deficiency, kidney function, pregnancy and lactation.", "uncertainty": "Gaps in direct results by strata of deficiency, kidney function, pregnancy and lactation.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Baseline B6 assessment; participants, pain and harm results by stratum; and selection/exclusion tables." }, { "item_id": "N05", "question_type": "Common background care", "question": "Are the actual comparator groups’ background care and placebo contents verified?", "needed": "Investigational-product and placebo composition; diet, medication, analgesics and rescue medication in both groups; and records of changes.", "role": "Required", "role_reason": "Needed to avoid wrongly attributing differences in concomitant or rescue medication to pyridoxine’s contribution to pain outcomes.", "application_exception": "Do not require every treatment change to be identical. Verify the actual effect of interest and how changes were handled in the analysis.", "criterion": "Link the actual content of background care and differences between groups, and do not infer that treatment was actually identical solely from instructions to maintain it.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M03 §3.2.3, M08 §8.2.2–8.2.3; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Define background care in both groups and record medication changes and rescue use, linking them to interpretation of assignment and adherence effects.", "current_reports": [ "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The question concerns placebo on the same background care. Levin recorded matching placebo tablets and instructions to maintain diet and medication, but placebo composition, analgesics and rescue medication in eligible NRS studies are unverified.", "condition_status": "Partly verified", "status_reason": "Placebo and maintenance instructions are recorded for the adjacent trial, but actual group-specific distributions of concomitant and rescue medication and changes in them have not been verified.", "missingness": "Gaps in background care, actual maintenance and changes, and placebo composition for a direct NRS comparison.", "uncertainty": "Gaps in background care, actual maintenance and changes, and placebo composition for a direct NRS comparison.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Investigational-product/placebo documents for each candidate, and tables of concomitant medication, rescue medication and changes by group." }, { "item_id": "N06", "question_type": "Dose", "question": "Are the actual dose and administration schedule for an eligible mean NRS comparison verified?", "needed": "The connection between actual dose, frequency, total B6 exposure and the corresponding NRS result; identification of totals derived from historical schedules.", "role": "Required", "role_reason": "Distinguishing an adjacent schedule from a dose with direct efficacy evidence prevents data conversion from becoming a new prescribing claim.", "application_exception": "Do not fill in actual intake from a nominal schedule. Do not recalculate the original total or conflate it with nutritional upper limits or an efficacious dose.", "criterion": "Attribute only doses recorded in the original report to the relevant trial, and do not use the total from an adjacent schedule as a dose with established efficacy or a dosing recommendation.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Link a verified monotherapy dose only to its study results. Review claims about an optimal dose separately, only when direct dose comparisons are available.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The adjacent Levin trial used 50 mg 3 times daily. The manuscript’s 150 mg/day is the total from the historical schedule. The dose for a direct mean NRS comparison is unverified.", "condition_status": "Partly verified", "status_reason": "The adjacent dose schedule is preserved, but an eligible dose used to assess NRS efficacy and actual total exposure have not been verified.", "missingness": "Gaps in the dose for direct NRS assessment and actual intake; 150 mg/day is a historical calculated value.", "uncertainty": "Gaps in the dose for direct NRS assessment and actual intake; 150 mg/day is a historical calculated value.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Dosing, adherence and product-specific B6 records for the candidates, and the source of the original dose calculation." }, { "item_id": "N07", "question_type": "Observation period", "question": "Are the measurement time point, treatment duration and post-discontinuation follow-up for eligible NRS results verified?", "needed": "Actual NRS collection time points; treatment, follow-up and discontinuation periods; and separate results on sustained effects.", "role": "Required", "role_reason": "Linking the endpoint to the observation period prevents old categorical observations from being read as sustained NRS effects.", "application_exception": "The current question does not require maintenance of the effect. Direct post-discontinuation follow-up is required only when extending the claim to sustained effects.", "criterion": "Do not transfer the adjacent 4-month categorical observation period to NRS assessment; leave post-discontinuation effects unverified when no data on them are available.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Prespecify the NRS assessment window and end time point, and examine sustained effects through separate estimates after treatment ends.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Levin’s duration is recorded as 4 months. Its results use study-specific symptom categories; eligible NRS time points and duration and pain follow-up after discontinuation are unverified.", "condition_status": "Partly verified", "status_reason": "The adjacent duration is verified, but it cannot be directly linked to mean NRS at the same time point or to sustained effects.", "missingness": "Gaps in NRS assessment time points, treatment duration and follow-up after discontinuation.", "uncertainty": "Gaps in NRS assessment time points, treatment duration and follow-up after discontinuation.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Visit schedules, pain tables, follow-up data and discontinuation data for each candidate." }, { "item_id": "N08", "question_type": "Pain scale", "question": "Did an actual eligible study use a validated mean pain NRS?", "needed": "Scale name, range, direction and validity; collection procedures and time points; and the definition of mean pain.", "role": "Required", "role_reason": "Without matching scales, responder counts and differences in mean pain cannot be compared as the same outcome.", "application_exception": "Do not enter 0–10 as the NRS range actually used. Preserve other scales with their original values and definitions, without automatic conversion.", "criterion": "Verify the scale actually used. Distinguish the question’s preferred range of 0–10 from actual instrument use, and do not convert VAS, categories or NTSS-6 to NRS.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / M08 Table 8.2.a, M03 §3.2.4; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Prespecify the validated NRS, collection window and direction, and report mixed pain-or-paresthesia categories separately.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The preferred NRS range for the question is 0–10. The preserved inputs state that the eligible instrument, time point and denominator are unverified and that VAS is separate.", "condition_status": "Unverified", "status_reason": "The NRS scale and collection method in an actual eligible study have not been verified, so the question’s scale preference alone cannot establish measurement eligibility.", "missingness": "Gaps in the direct NRS measurement instrument and assessment procedures.", "uncertainty": "Gaps in the direct NRS measurement instrument and assessment procedures.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Pain measurement instruments and collection descriptions in the candidates’ original reports and protocols." }, { "item_id": "N09", "question_type": "Categorical scale", "question": "Are Levin’s −1/0/+1/+2 categories eligible as direct mean NRS results?", "needed": "The meaning of the original symptom categories, their pain/paresthesia composition and measurement differences from NRS.", "role": "Required", "role_reason": "Separating known ineligible scales prevents them from filling gaps in eligible pain-effect results.", "application_exception": "This Not met status applies only to the categorical results currently preserved. It does not deny the existence of separate results that have not been verified.", "criterion": "Use a result as a direct endpoint only when it is a validated mean NRS result. Do not interpret study-specific ordinal categories as an equal-interval continuous scale.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / M08 Table 8.2.a, M03 §3.2.4; custom application / M08 §8.2.2, M15 §15.3.1; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Extract ordinal categories using their original definitions and check whether direct NRS results were reported separately. Do not invent means or standard deviations.", "current_reports": [ "S01", "S02" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Levin used study-specific symptom-change categories: worse −1, unchanged 0, slight improvement +1 and substantial improvement +2. The manuscript did not convert these to a validated NRS.", "condition_status": "Not met", "status_reason": "The currently known Levin results differ from the fixed mean NRS endpoint. This does not constitute a judgment of no effect in Levin or failure of the entire trial.", "missingness": "Direct mean NRS cannot be derived from these categories; whether separate NRS results were reported is unverified.", "uncertainty": "Direct mean NRS cannot be derived from these categories; whether separate NRS results were reported is unverified.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "The complete original pain measurements and results from Levin, and whether NRS was reported separately." }, { "item_id": "N10", "question_type": "Responder counts", "question": "Do 6/9 versus 4/9 represent mean NRS or a 50% pain-response rate?", "needed": "The original response definition, pain/paresthesia composition, denominator for each response and distinction from mean pain outcomes.", "role": "Required", "role_reason": "Reading responder counts as a mean difference or as a different response criterion misattributes both the effect and the denominator.", "application_exception": "Do not delete favorable response records. Do not treat the original categorical result as an effect of 0 because it is ineligible for mean NRS.", "criterion": "Use a result as mean NRS or a prespecified 50% pain response only when it measures that outcome. Do not turn the substantial-symptom-improvement category into another measure.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / M08 §8.2.2, M15 §15.3.1; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Report mean pain and prespecified response measures separately, linking each result to its denominator.", "current_reports": [ "S01", "S02" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Substantial improvement in pain or paresthesia in the B6 group, 6/9 participants, and the placebo group, 4/9 participants, was preserved. This is the original response category, not a mean NRS/VAS difference or a 50% pain-response rate.", "condition_status": "Not met", "status_reason": "The response defined in the manuscript is a different measure from the fixed mean NRS, and a 50% threshold cannot be verified. No new effect rate, OR or P value was constructed from these counts.", "missingness": "No connection to direct mean NRS or to a 50% response criterion.", "uncertainty": "No connection to direct mean NRS or to a 50% response criterion.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "The original response definition, participant-level distinctions between pain and paresthesia, and separate NRS tables." }, { "item_id": "N11", "question_type": "Participant flow", "question": "Can the denominators for allocation, symptom response, completion, and NRS analysis be distinguished?", "needed": "Allocation and participant flow by group, symptom-response denominators, visit completion, and counts measured and analyzed for NRS.", "role": "Required", "role_reason": "Needed to avoid transferring a verified sample size to the analysis denominator for an unverified pain outcome.", "application_exception": "Do not state that there were no participants because a denominator is empty. Keep the McCann/Cohen denominators unverified in their separate candidate records.", "criterion": "Link only the originally provided denominator to its corresponding result; do not infer completion of all visits or the direct NRS analysis count from 18 participants and 9/9.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design / M08 §8.2.2, M15 §15.3.1; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Extract allocation, measurement, completion, and analysis denominators for each endpoint/visit, without using them interchangeably.", "current_reports": [ "S01", "S02" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Levin's total allocation was 18 participants, and the group denominators for the symptom categories were 9/9. NRS analysis n and the total completion count are empty values, and the record cautions against inferring completion of all visits from 9/9.", "condition_status": "Partly verified", "status_reason": "Allocation and categorical-response denominators are verified, but denominators for completion, visits, and direct NRS analysis are unverified.", "missingness": "Gaps in completion counts, measurement/analysis counts by endpoint, and visit flow.", "uncertainty": "Gaps in completion counts, measurement/analysis counts by endpoint, and visit flow.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Participant flow diagrams by group and tables of visits, pain measurements, and analyses." }, { "item_id": "N12", "question_type": "Mean pain values", "question": "Can baseline, change, and endpoint mean NRS values be directly verified?", "needed": "Group-specific baseline, change, and endpoint NRS means, units, time points, and analysis populations.", "role": "Required", "role_reason": "The lack of available mean values is a key gap that prevents direct evaluation of the pain effect of interest.", "application_exception": "Do not use means of indirect biomarkers as NRS before obtaining eligible results. Do not conclude that the values are unreported anywhere in a full text that has not been read.", "criterion": "Each mean must be linked to an actual NRS measure, group, and time point. Do not fill these fields with general symptoms, nerve conduction, PLP, or fasting glucose.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations use a custom design / M08 §8.2.2, M15 §15.3.1; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Extract baseline, change, and endpoint values separately and specify in advance the between-group effect to be estimated.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The retained manuscript leaves baseline, change, and endpoint mean pain values unverified. The mean_changes field in the calculation structure is also empty; nerve conduction, PLP, fasting glucose, and general symptom relief were not used as substitutes.", "condition_status": "Unverified", "status_reason": "The current input contains no results table from which group-specific NRS means can be read directly. An empty value does not mean a mean of 0.", "missingness": "Gaps in direct NRS baseline, change, and endpoint means and time points.", "uncertainty": "Gaps in direct NRS baseline, change, and endpoint means and time points.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Group-specific pain results tables and analysis definitions for eligible candidates." }, { "item_id": "N13", "question_type": "Variance and error", "question": "Are the SD, SE, sample size, and type of error statistic for direct NRS results verified?", "needed": "Group-specific variances for NRS changes/endpoint values, the SD/SE labels and n, and covariance and model descriptions where needed.", "role": "Required", "role_reason": "Direct interpretation of significance or CIs is not possible without the original type of error statistic and denominator.", "application_exception": "Do not assign a new low-precision grade solely because variance is unavailable. Do not transfer values from an ineligible scale into NRS variance.", "criterion": "Verify the actual type of error statistic, endpoint, time point, and denominator; do not reconstruct unreported variance from categorical responses.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design / M15 §15.3.1–15.3.3; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Extract the original values while distinguishing SD from SE, and record the endpoint, time point, group, and denominator together. Do not insert arbitrary correlations or variances.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The sd_changes, standard_error, and n fields in the calculation structure are all empty. The original methods description states that unreported statistics were not reconstructed because eligible mean NRS inputs were unavailable.", "condition_status": "Unverified", "status_reason": "Without material verifying direct NRS variance and the type of error statistic, the inputs needed to judge precision cannot be linked.", "missingness": "Gaps in SD/SE, variance, and the corresponding n.", "uncertainty": "Gaps in SD/SE, variance, and the corresponding n.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Statistical notes, variance, n, and analysis models for the direct NRS results tables." }, { "item_id": "N14", "question_type": "Between-group estimation", "question": "Are the between-group difference, CI, P value, and effect of interest for the fixed NRS question verified?", "needed": "Effects of assignment/adherence, the model, direction, CI, P value, and analysis denominator for the difference in changes or endpoint values.", "role": "Required", "role_reason": "A pain-effect estimate versus placebo cannot be constructed from mean values or counts of favorable responses alone.", "application_exception": "Do not interpret an uncalculated estimate as a finding of no difference. If the original P value is unavailable, do not label the result nonsignificant.", "criterion": "Link only actual between-group NRS estimates and intervals; do not fill gaps by calculating differences, CIs, or P values from within-group improvement or categorical responses.", "basis": "M08 §8.2.2, M15 §15.3.1; custom application / M15 §15.3.1–15.3.3; custom application / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations use a custom design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Specify whether the effect of interest is the effect of assignment or adherence, and report baseline adjustment, handling of missing data, and the direction and CI of the between-group estimate.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "In the manuscript, the between-group NRS difference, CI, and P value are unverified. The calculation fields difference, df, confidence_level, and interval are empty, and the status is not calculated because eligible inputs are unverified.", "condition_status": "Unverified", "status_reason": "Without an analysis population, model, or direct NRS estimate, the direction, magnitude, and interval of the between-group effect cannot be verified.", "missingness": "Gaps in the between-group NRS estimate, CI, P value, model, and denominator.", "uncertainty": "Gaps in the between-group NRS estimate, CI, P value, model, and denominator.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "The candidate's analysis plan, between-group pain results, and statistical explanation." }, { "item_id": "N15", "question_type": "Clinical importance", "question": "Is there an applicable threshold for an important difference with which to interpret the direct NRS effect?", "needed": "An MCID or justified important difference for the same population, scale, and assessment window, together with the interval for the direct effect.", "role": "Required", "role_reason": "Significance or participant counts alone cannot establish the clinical meaning of pain improvement.", "application_exception": "Do not fill the gap by proposing unsupported numerical thresholds. If no importance threshold is available, retain the manuscript's unverified status.", "criterion": "Compare thresholds supported by actual sources with direct NRS intervals. Do not invent universal minimum participant counts, durations, trial counts, or an arbitrary MCID.", "basis": "M15 §15.3.1–15.3.3; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Prespecify the evidence and scope of applicability for an important difference, and distinguish the magnitudes of benefit, no difference, and unfavorable effects compatible with the CI.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The manuscript leaves an applicable MCID unverified. Direct NRS effects and CIs are also unavailable, so the relationship between clinical importance and precision cannot be assessed.", "condition_status": "Unverified", "status_reason": "Supporting evidence for an applicable important difference and a direct interval have not been obtained. The response-category label \"substantial improvement\" is not an MCID.", "missingness": "Gaps in valid evidence for an important difference and a direct interval.", "uncertainty": "Gaps in valid evidence for an important difference and a direct interval.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Evidence on clinical importance for the relevant painful DSPN population and NRS, and eligible between-group estimates." }, { "item_id": "N16", "question_type": "Allocation and design", "question": "Can actual allocation, concealment, and baseline balance be verified?", "needed": "Parallel/crossover/cluster structure, random-sequence generation and allocation-concealment procedures, and baseline characteristics by group.", "role": "Required", "role_reason": "Known allocation descriptions must be distinguished from unverified concealment and baseline balance to assess actual comparability.", "application_exception": "Do not preassign NA to crossover or cluster-design issues for a candidate whose design is unverified. A record of randomization does not automatically establish absence of bias.", "criterion": "Link the actual methods to their results, and do not mark allocation, concealment, or confounding issues as resolved on the strength of an RCT label alone.", "basis": "M08 §8.1–8.2.3; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Verify the actual parallel/crossover/cluster structure and link the handling of allocation, clusters, and periods for each design to the pain outcome of interest.", "current_reports": [ "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Levin is recorded as a pharmacy-randomized, double-blind, parallel, placebo-controlled trial; detailed allocation concealment is unverified. McCann is a controlled trial according to its title and Cohen is indexed as a clinical trial, but detailed methods are unverified.", "condition_status": "Partly verified", "status_reason": "Design information exists for the adjacent Levin trial, but the allocation process and baseline balance for direct NRS results, and the actual designs of the older candidates, have not been sufficiently verified.", "missingness": "Gaps in allocation-sequence generation, concealment, baseline balance, and the unverified candidate designs.", "uncertainty": "Gaps in allocation-sequence generation, concealment, baseline balance, and the unverified candidate designs.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Methods sections, randomization procedures, and baseline tables for each candidate." }, { "item_id": "N17", "question_type": "Assessment blinding", "question": "Are blinding and collection procedures for subjective pain assessment verified?", "needed": "Blinding of participants, care providers, and assessors; placebo appearance; NRS collection methods; and differences in measurement between groups.", "role": "Required", "role_reason": "Patient-reported pain must be reviewed in relation to the actual collection and blinding conditions.", "application_exception": "Do not treat inability to blind as an automatic failure. A double-blind label does not establish eligibility of direct NRS measurement.", "criterion": "Distinguish a double-blind description from actual pain-collection procedures, and do not assign successful blinding or absence of measurement bias without evidence.", "basis": "M08 Table 8.2.a, M03 §3.2.4; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Specify the NRS collection window, who collects it, handling of omissions, and identical procedures across groups, and examine actual limitations in blinding.", "current_reports": [ "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Levin is recorded as double-blind with matching placebo tablets. Its results use its own categories, however, and direct NRS assessment, blinding success, and collection procedures by group are unverified.", "condition_status": "Partly verified", "status_reason": "Although the adjacent trial is labeled as blinded, the measurement conditions for the fixed NRS endpoint cannot be verified, so the overall measurement conditions remain unverified.", "missingness": "Gaps in direct NRS collection, assessment blinding, and whether blinding succeeded.", "uncertainty": "Gaps in direct NRS collection, assessment blinding, and whether blinding succeeded.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "The candidate's assessment procedures, placebo description, pain-collection procedures, and blinding materials." }, { "item_id": "N18", "question_type": "Adherence and rescue medication", "question": "Can actual adherence, analgesics, rescue medication, and treatment changes be verified?", "needed": "Actual intake and adherence by group, concomitant analgesics, rescue medication, treatment changes, and their handling in the analysis.", "role": "Required", "role_reason": "Deviations from treatment and other pain-relief interventions may explain differences in pain, so they need separate documentation.", "application_exception": "Do not require every change to be identical. The current unverified status does not establish nonadherence or unequal treatment.", "criterion": "Distinguish maintenance instructions from actual behavior, and link the handling of changes by group to their impact on the effect of interest.", "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; custom application / M08 §8.2.2, M15 §15.3.1; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Distinguish the effect of assignment from the effect of adherence, and report and analyze rescue medication and treatment changes in a prespecified manner.", "current_reports": [ "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The manuscript records that adherence, exact analgesics, and rescue medication were not sufficiently verified. Instructions to maintain diet and medication were not used as evidence of actual adherence.", "condition_status": "Unverified", "status_reason": "The current input does not verify the numbers or methods concerning actual adherence, concomitant treatment, rescue use, or their effects on group-specific analyses.", "missingness": "Gaps in group-specific records of adherence, concomitant treatment, treatment deviations, and rescue medication.", "uncertainty": "Gaps in group-specific records of adherence, concomitant treatment, treatment deviations, and rescue medication.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Candidate-specific tables of dosing, concurrent treatments, rescue medication, and treatment deviations, with analysis plans." }, { "item_id": "N19", "question_type": "Missing data and analysis populations", "question": "Are NRS missingness, dropouts, and the actual analysis populations and handling verified?", "needed": "Reasons for missing NRS data and dropouts at each visit, ITT/PP, analysis n, handling of missing data, and sensitivity analyses.", "role": "Required", "role_reason": "Missing data and actual analysis counts are directly needed to interpret mean pain estimates.", "application_exception": "Do not convert unverified missingness into confirmed attrition bias or 0 dropouts. Also retain the existence of ineligible categorical results.", "criterion": "Verify the original analysis population and endpoint-specific missingness, without inferring NRS ITT populations or completion counts from allocation counts or categorical denominators.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design / M08 §8.2.2, M15 §15.3.1; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Extract endpoint-specific missingness and reasons by group, and prespecify analysis and sensitivity methods appropriate to the effect of interest.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The manuscript leaves completion of all visits and endpoint-specific missingness unverified. It does not infer NRS analysis counts from categorical-response denominators, and actual NRS ITT/PP and missing-data handling have not been verified.", "condition_status": "Unverified", "status_reason": "There is no direct record of the pain analysis population, endpoint-specific flow, or handling of missing data. Allocation of 18 participants does not establish the NRS analysis n.", "missingness": "Gaps in NRS missingness, dropouts, analysis populations, and sensitivity data.", "uncertainty": "Gaps in NRS missingness, dropouts, analysis populations, and sensitivity data.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Visit-specific NRS data flow, dropout tables, and analysis plans/descriptions of missing-data handling." }, { "item_id": "N20", "question_type": "Plans and selective reporting", "question": "Can prespecified pain endpoints, analyses, and time points be compared with actual reporting?", "needed": "Registrations, protocols, and analysis plans for monotherapy candidates; pain-endpoint hierarchy, time points, multiplicity, and reasons for changes.", "role": "Required", "role_reason": "Comparison with actual plans is needed to avoid treating the current results gap as proof of selective reporting.", "application_exception": "An unavailable plan for an older trial is not proof that it was unregistered. Do not attach the registration of a different combination trial to a monotherapy candidate.", "criterion": "Compare only plans and results that have actually been obtained. Do not describe an unavailable plan as proof of nonregistration or selective reporting.", "basis": "M08 Table 8.2.a, M04 §4.6.3; custom application / M04 §4.5, §4.6.3; limits on the current conversion of the material reflect the user-defined scope and custom design", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Compare prespecified pain endpoints, analyses, and time points with actual results, and separately record reasons for changes and multiple comparisons.", "current_reports": [ "S02", "S03", "S04", "S05", "S08" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The manuscript leaves the prospective protocol, multiplicity, and selective reporting unverified. Metanx's NCT00726713 and the combination registration NCT04689971 do not substitute for a monotherapy candidate's prospective NRS plan.", "condition_status": "Unverified", "status_reason": "Materials comparing plans with results for direct monotherapy NRS candidates have not been obtained, so whether selective reporting occurred cannot be verified.", "missingness": "Gaps in comparisons of prospective plans, endpoint hierarchies, and changes for monotherapy candidates.", "uncertainty": "Gaps in comparisons of prospective plans, endpoint hierarchies, and changes for monotherapy candidates.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Registration, protocol, analysis plan, and correction/result reports for each monotherapy candidate." }, { "item_id": "N21", "question_type": "McCann candidate", "question": "Can the monotherapy, comparator, pain scale, and results of McCann 1983 be directly verified?", "needed": "The original article's methods, formulation/dose, comparator, population, pain instrument, and results/denominators, and their agreement with the review's citation.", "role": "Required", "role_reason": "Unverified monotherapy candidates must be retained to describe honestly the scope of the current direct-evidence gap.", "application_exception": "Do not present control and blinding mentioned in a title as verified details of the methods. A review's mention of a candidate does not establish that the full text was read or that direct results were obtained.", "criterion": "Do not use bibliographic titles or clues from reviews as original numerical results. Use full-text results to verify whether an eligible mean NRS was reported.", "basis": "M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract use a custom design / M03 §3.2.1; detailed population conditions use a custom design / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations use a custom design / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations use a custom design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses uses a custom design", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "If the full text is obtained, verify the population, monotherapy intervention, comparator, scale, and denominators, and record new reasons for inclusion/exclusion. Hold review-level numbers pending verification.", "current_reports": [ "S03", "S15" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The McCann candidate has only verified bibliographic information and publication type. Its title indicates a double-blind controlled study, but its dose, schedule, pain instrument, original results, and denominators are unverified; primary_NRS_result and analysis n are empty values.", "condition_status": "Unverified", "status_reason": "The original numbers cannot be read, and limitations on full-text access do not establish a finding of no effect or the absence of direct NRS results.", "missingness": "Gaps in McCann's original methods, results, and eligibility.", "uncertainty": "Gaps in McCann's original methods, results, and eligibility.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "McCann's original article, supplementary results, any corrections, and the corresponding primary reference in the review." }, { "item_id": "N22", "question_type": "Cohen candidate", "question": "Can the pain instrument, comparator, and direct results of Cohen 1984 be verified?", "needed": "The original article's population, single-ingredient composition, design, pain instrument/time point, denominators, and results, together with the actual access history.", "role": "Required", "role_reason": "Retain its status as a separate candidate to avoid confusing failed access with negative pain findings.", "application_exception": "Do not label the absence of an external access attempt in this review as inaccessibility. Do not infer from original metadata alone that all the information is unreported in the full text.", "criterion": "Do not use PubMed metadata or the publisher403 record from that time as original results. Verify direct NRS eligibility after obtaining the results.", "basis": "M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract use a custom design / M03 §3.2.1; detailed population conditions use a custom design / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations use a custom design / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations use a custom design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses uses a custom design", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "After obtaining the original text, screen the single ingredient, population, comparator, and scale, and link only the pain results that can actually be verified.", "current_reports": [ "S04" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "For Cohen, bibliographic information without an abstract and clinical-trial indexing are retained. A publisher 403 was recorded at the time, but no access was attempted in this review; the direct pain instrument, time point, hierarchy, results, and denominators remain unverified.", "condition_status": "Unverified", "status_reason": "Eligible pain results cannot be assessed because the original results have not been obtained. The historical 403 is not a finding of no effect and is not retrospectively counted as a failure in this review.", "missingness": "Gaps in Cohen's original results, methods, scale, and denominators; historical access failure.", "uncertainty": "Gaps in Cohen's original results, methods, scale, and denominators; historical access failure.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Cohen's original article, supplementary results, methods, corrections, and lawful access routes." }, { "item_id": "N23", "question_type": "Study families and missing identities", "question": "Are all links between reports and actual study families verified?", "needed": "Correspondence between report IDs, DOI/PMID, families, and the original material list, and the identity of missing references.", "role": "Required", "role_reason": "Needed to distinguish report counts from study counts and avoid mistaking a missing reference for replicated numerical evidence.", "application_exception": "When a material's identity is missing, do not delete it or treat it as a confirmed entry in the actual material list. Do not convert the total family count into a count of direct NRS replications.", "criterion": "Do not add together an abstract, an author-provided full text, and a review of the same study; leave an ID absent from the list as an unverified link.", "basis": "M04 §4.6.1–4.6.2 distinguishes studies from reports; cohort/result linkage is a custom application / M04 §4.5–4.6 provides principles for material collection/selection; separating access from reading and the hyperlink contract are custom-designed / M04 §4.6.1–4.6.2, M15 §15.3.1; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Link report→study family→endpoint/timepoint/analysis, and manage missing IDs as provisional references until verified.", "current_reports": [ "S01", "S02", "S03", "S15" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The S01 abstract and S02 author-deposited full text belong to the same Levin study family. Although 7 evidence families are recorded, S17 in McCann's linked source list is absent from the actual citations S01–S15; its identity and original text remain unverified.", "condition_status": "Partly verified", "status_reason": "Levin's shared study family and links to the main candidates are verified, but S17 cannot be linked to an actual report. It was neither invented nor counted as an independent trial.", "missingness": "The current identity/source material for S17 in the McCann family is missing; the number of unique eligible trials remains undetermined.", "uncertainty": "The current identity/source material for S17 in the McCann family is missing; the number of unique eligible trials remains undetermined.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Original identity documentation for the S17 reference and a table linking included trials and reports for each candidate." }, { "item_id": "N24", "question_type": "Metanx combination", "question": "Does Metanx provide a direct comparison of mean NRS for pyridoxine hydrochloride alone?", "needed": "Full PLP/folate/B12 composition, primary VPT/secondary NTSS-6, and results isolating the B6 contribution.", "role": "Required", "role_reason": "Needed to prevent misattribution to monotherapy while retaining favorable combination results.", "application_exception": "Do not label results for the combination as showing no effect. Do not convert VPT/NTSS-6 to NRS.", "criterion": "Include only when the specified monotherapy intervention and mean NRS are directly linked. Do not use combination results as direct effects when the contributions of other ingredients have not been separated.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation for each question is custom-designed / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed / M03 §3.2.3, M08 §8.2.2–8.2.3; custom application / M03 §3.2.4; custom limits on extensions", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Retain combination results by study family and separately check for monotherapy comparisons or comparisons isolating component contributions.", "current_reports": [ "S05" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Metanx combines L-methylfolate calcium, methylcobalamin and PLP. Primary vibration perception threshold and secondary NTSS-6 are not mean NRS; favorable secondary results were not attributed to B6 alone.", "condition_status": "Not met", "status_reason": "The intervention composition and endpoint both differ from the fixed question. Favorable secondary results are retained, but they cannot fill the gap in evidence for the effect of pyridoxine alone on NRS.", "missingness": "No link between the monotherapy contribution and direct mean NRS results.", "uncertainty": "No link between the monotherapy contribution and direct mean NRS results.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Original Metanx methods, composition, primary/secondary results, and direct data isolating component contributions." }, { "item_id": "N25", "question_type": "Metabolic and oxidative markers", "question": "Do Dawood's metabolic and oxidative-stress results directly answer the painful DSPN NRS question?", "needed": "The newly diagnosed T2DM/metformin population, actual pain diagnosis and endpoints, and a comparison of B6 alone.", "role": "Required", "role_reason": "Shared references to diabetes and vitamins alone do not justify treating metabolic markers as patient-reported pain outcomes.", "application_exception": "Do not erase the significance of the verified metabolic study. Do not conclude that other results are absent from an unread original.", "criterion": "Do not substitute oxidative-stress or metabolic results for the same pain outcome; verify alignment of the actual population, intervention and NRS.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed / M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation for each question is custom-designed / M03 §3.2.4; custom limits on extensions", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Extract biomarkers as separate outcomes and verify whether painful DSPN and direct NRS results were actually reported.", "current_reports": [ "S06" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Dawood was recorded as a metabolic/oxidative-stress study involving newly diagnosed T2DM/metformin. Metabolic results for B6 and metformin were not used as analgesic effects.", "condition_status": "Not met", "status_reason": "The retained population and endpoint differ from the fixed question of mean NRS in painful DSPN. Results for other biomarkers cannot fill the gap left by unverified NRS results.", "missingness": "No direct link to the specified population and mean NRS.", "uncertainty": "No direct link to the specified population and mean NRS.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Complete original definitions of Dawood's participant selection, intervention, metabolic outcomes and pain outcomes." }, { "item_id": "N26", "question_type": "Uncontrolled foot pain", "question": "Is Bae's foot-pain improvement an eligible diabetes-specific NRS result versus placebo?", "needed": "A separately identified diabetic DSPN population, pain instrument, comparison group, denominator, timepoint and between-group estimate.", "role": "Required", "role_reason": "Before-and-after improvement and an effect versus placebo are different estimates, so the actual study design must be verified.", "application_exception": "Retain uncontrolled reports as well. Do not state that there was no improvement or that the monotherapy effect was 0 merely because there was no comparison.", "criterion": "Do not treat uncontrolled improvement in a mixed population as a control-adjusted effect; verify that the specified population and actual comparison align.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed / M08 §8.1–8.2.3; custom application / M08 §8.2.2, M15 §15.3.1; custom application / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Retain mixed-population results within their original scope and check whether separate controlled results exist for the specified population.", "current_reports": [ "S07" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Bae is a retrospective, uncontrolled report of heterogeneous foot pain related to peripheral nerves. The description of improvement was retained, but a mean NRS estimate for diabetic pain versus placebo was not verified.", "condition_status": "Not met", "status_reason": "The currently known study has no control group, and direct separation of the specified population and outcome remains unverified. The description of improvement cannot be used as a between-group monotherapy effect.", "missingness": "No direct link to a separately identified diabetic population and a placebo-controlled NRS estimate.", "uncertainty": "No direct link to a separately identified diabetic population and a placebo-controlled NRS estimate.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Bae's original population, pain scale, timepoints, participant flow and any available comparison data." }, { "item_id": "N27", "question_type": "Registry scope", "question": "Can the use of monotherapy, latest status and pain results for NCT04689971 be verified?", "needed": "Intervention composition, population, endpoints, status and results in the official registration, together with the extent to which the material has actually been obtained.", "role": "Required", "role_reason": "The existence of an official registry URL alone does not establish that results have been made public or read, or that the intervention is eligible as monotherapy.", "application_exception": "Do not treat a registry record that has not been obtained as evidence of no trial or a result of 0. Do not recast the historical shell record as a failure in this review.", "criterion": "Do not treat the indexed description and application shell as complete registry results. Do not link the B1/B6/B12 combination to B6 monotherapy.", "basis": "M04 §4.5–4.6 provides principles for material collection/selection; separating access from reading and the hyperlink contract are custom-designed / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M04 §4.5, §4.6.3; limits on the current data conversion follow the user-defined scope and custom design / M08 Table 8.2.a, M04 §4.6.3; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Link registration, results and publication reports within study families, distinguishing planned information from actual results.", "current_reports": [ "S08" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "NCT04689971 is an indexed description of a combination registration adding B1·B6·B12 to standard treatment. The direct page at the time was an application shell; the latest status, actual results and denominators remain unverified.", "condition_status": "Partly verified", "status_reason": "The registry identity and combination-intervention description were recorded, but the full registration, current status and results could not be verified. They cannot be directly linked to the monotherapy NRS question.", "missingness": "Gaps in the registry text, latest status and actual results/denominators; mismatch with monotherapy.", "uncertainty": "Gaps in the registry text, latest status and actual results/denominators; mismatch with monotherapy.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Complete intervention, endpoint, result and amendment history from the official registration." }, { "item_id": "N28", "question_type": "Guideline context", "question": "Can a direct NRS effect of B6 alone be verified from the ADA/AAN guidelines?", "needed": "The guidelines' actual recommendations and evidence links, and results from the relevant monotherapy pain trials.", "role": "Supplementary; essential for interpreting clinical context", "role_reason": "Needed to avoid conflating clinical recommendations with a specific ingredient's direct effect estimate.", "application_exception": "This table is not a guideline replacing existing pain treatment. Do not infer the absence of original studies solely from a guideline's list.", "criterion": "Distinguish guidelines used as clinical context from direct effect evidence; do not use absence from a recommendation list as evidence of no effect.", "basis": "M04 §4.5–4.6 provides principles for material collection/selection; separating access from reading and the hyperlink contract are custom-designed / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed / M04 §4.5, §4.6.3; limits on the current data conversion follow the user-defined scope and custom design", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Check the studies underlying recommendations against the original question; do not use the absence of a recommendation as an exclusion reason or as an effect of 0.", "current_reports": [ "S09", "S10" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The ADA and AAN guidelines were recorded solely as clinical context for diabetic neuropathic pain. The absence of B6 from recommendation lists was not used to judge an effect of 0 or to add or deduct points.", "condition_status": "Partly verified", "status_reason": "The guidelines' identity and role are verified, but direct material providing the fixed mean NRS estimate for monotherapy has not been verified in the current input.", "missingness": "Gap between guideline context and a direct NRS estimate for monotherapy.", "uncertainty": "Gap between guideline context and a direct NRS estimate for monotherapy.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "The relevant guideline evidence tables and recommendations, linked to the actual original trials." }, { "item_id": "N29", "question_type": "Result direction and conflicting findings", "question": "Can the favorable, no-difference and unfavorable directions of unique eligible NRS results be compared together?", "needed": "Between-group NRS estimates and intervals from unique eligible trials, and differences in populations, interventions, timepoints and analyses.", "role": "Required", "role_reason": "Needed to avoid filling gaps with only favorable adjacent results or treating dissimilar results as conflicts.", "application_exception": "Do not turn statistical nonsignificance into an effect of 0 or equivalence. Differences across scales or populations do not automatically constitute conflicting data.", "criterion": "Compare only direct results addressing the same question; do not turn differences involving ineligible scales or unverified results into data conflicts or findings of no difference.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed / M04 §4.6.1–4.6.2, M15 §15.3.1; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Attribute results in every direction to their study family, endpoint, timepoint and analysis, and record only actual conflicts concerning the same question, together with reasons.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S07" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Levin's categorical improvement, favorable secondary NTSS-6 records for Metanx, and Bae's improvement are retained. Direct NRS results remain unverified, so agreement, no difference or conflict among eligible results cannot be assessed.", "condition_status": "Unverified", "status_reason": "Ineligible and unverified results cannot be pooled into a single NRS estimate, so the distribution of direct effect directions remains undetermined. Access failures were not used as negative results.", "missingness": "Gaps in the directions, conditions and intervals of unique eligible NRS results.", "uncertainty": "Gaps in the directions, conditions and intervals of unique eligible NRS results.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Complete results for each candidate, including no-difference and unfavorable results, and corrections." }, { "item_id": "N30", "question_type": "Product supply and conflicts of interest", "question": "Can product supply, research funding, author conflicts of interest and independence be verified?", "needed": "Supply of the active agent and placebo, full funding, employment, patents, disclosed COI, and links to institutions/study families.", "role": "Supplementary; essential for claims of independence", "role_reason": "The actual scope of disclosures must be explained without treating product supply as independent funding or proof of bias.", "application_exception": "Do not discard results because of company involvement. Do not state that there are no conflicts of interest because disclosures could not be read.", "criterion": "Distinguish verified supply arrangements from unverified full funding and COI; do not automatically grant independence or automatically exclude company-related results.", "basis": "Chamgap's own conditions for independence and attribution. The official methods sections used in this pilot do not validate all the details of this item / M04 §4.6.1–4.6.2 distinguishes studies from reports; cohort/result linkage is a custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Extract funding, product supply and author relationships from the original text, and review the independence claim and relevance to the results separately.", "current_reports": [ "S02", "S05" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Levin's active agent and placebo are recorded as supplied by Hoffman LaRoche. Full financial support, employment, patents and author COI remain unverified. Metanx's product company is identified, but full funding and COI remain unverified.", "condition_status": "Partly verified", "status_reason": "Product-supply information is available, but full research funding and author relationships have not been verified, so independent funding or independent replication cannot be established.", "missingness": "Gaps in full funding, author COI and institutional relationships.", "uncertainty": "Gaps in full funding, author COI and institutional relationships.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Funding/COI wording, product supply, institutions and related reporting information for each candidate." }, { "item_id": "N31", "question_type": "Neuropathy harms", "question": "Can harm events, denominators and collection methods be verified for the same exposure and population?", "needed": "Definitions, collection, severity and discontinuations relating to new/worsening sensory neuropathy, plus group-specific counts of people with events, exposure denominators and duration.", "role": "Supplementary; essential for interpreting safety", "role_reason": "Similar neuropathy symptoms can be treatment targets and harm events, so separate verification is needed.", "application_exception": "Do not remove efficacy data because harms were not reported. Do not expand the finding into a claim that all food intake is dangerous or that this trial established harm.", "criterion": "Do not use official warnings as incidence or causal estimates from efficacy trials; link actual events and denominators for the same exposure/population with their limitations.", "basis": "M19 §19.1.2–19.2.4; custom application / M19 §19.1.2–19.2.4; detailed distinctions are custom-designed / M19 §19.1.2–19.2.4, M04 §4.6.3; custom application / Chamgap's own interpretation limits. M19 principles are referenced; no official causality tool was applied", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Define new/worsening events separately from efficacy, and collect information on those exposed, counts of people with events, duration and discontinuations. Distinguish spontaneous reports from incidence.", "current_reports": [ "S11", "S12", "S13" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The manuscript records the possibility that B6 supplementation itself can cause peripheral or sensory neuropathy as official safety context. This does not mean that increased harm was demonstrated in this efficacy trial; event denominators and collection methods for the same population and dose remain unverified.", "condition_status": "Partly verified", "status_reason": "Official harm warnings are retained, but group-specific events, denominators and collection methods for the fixed question could not be verified. The existence of a warning is not an individual risk rate or a safety determination.", "missingness": "Gaps in event definitions, counts of people, denominators and systematic collection for the same population and exposure.", "uncertainty": "Gaps in event definitions, counts of people, denominators and systematic collection for the same population and exposure.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Harm and discontinuation result tables for the candidates, and the actual harm data cited by official warnings." }, { "item_id": "N32", "question_type": "Timing of harms and recovery", "question": "Can the minimum dose and duration associated with risk of harm, and recovery after discontinuation, be verified?", "needed": "Timing of exposure initiation, duration, event onset/worsening, discontinuation and recovery, with the relevant population and products.", "role": "Supplementary; essential for claims about timing and safety thresholds", "role_reason": "Needed to avoid turning gaps in temporal relationships into a safe dose or a guarantee of recovery.", "application_exception": "Do not create a new probability of permanent damage from a lack of improvement after discontinuation. An unverified minimum dose associated with risk does not mean equal risk at every dose.", "criterion": "Link only verified temporal relationships; do not estimate a minimum threshold, complete recovery or recovery timing.", "basis": "M19 §19.2 addresses harm questions by study design; temporal-relationship details are custom-designed / M19 §19.1.2–19.2.4; custom application / Chamgap's own interpretation limits. M19 principles are referenced; no official causality tool was applied", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Extract temporal sequence and the course after discontinuation from individual records; do not extrapolate recovery or thresholds beyond the observation period.", "current_reports": [ "S11", "S12" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The retained TGA context explains that risk is not ruled out below 50 mg/day and that a minimum dose or duration associated with risk has not been established. It does not guarantee complete recovery or its timing after discontinuation.", "condition_status": "Unverified", "status_reason": "No actual event-timing or recovery data are available for the specified efficacy population, and the manuscript does not provide a minimum threshold or guarantee of recovery.", "missingness": "Gaps in event timing, minimum thresholds and recovery estimates for the same exposure.", "uncertainty": "Gaps in event timing, minimum thresholds and recovery estimates for the same exposure.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Timelines of exposure, discontinuation and events/recovery, and harm reports with adequate follow-up." }, { "item_id": "N33", "question_type": "Overlapping exposures and causes", "question": "Can all B6 products, concomitant medicines and other causes of symptom worsening be verified?", "needed": "Total exposure by food, supplements/medicines and vitamers, concomitant medicines, underlying disease, and alternative causes of new/worsening symptoms.", "role": "Supplementary; essential for extensions to causality and individual safety", "role_reason": "Distinguishing tingling as a target of efficacy from supplementation-related harm requires verification of concurrent exposures and alternative causes.", "application_exception": "Do not decide on an individual's products or treatment in the current data conversion. Do not state that other causes were absent because information on alternatives is unavailable.", "criterion": "Separately verify the effects of multiple products and underlying disease; do not automatically attribute symptom worsening to diabetes or a single product.", "basis": "M19 §19.2.2–19.2.4 provides design considerations; detailed recording of confounding is custom-designed / Chamgap's own interpretation limits. M19 principles are referenced; no official causality tool was applied / M03 §3.2.3, M08 §8.2.2–8.2.3; custom application / M19 §19.1.2–19.2.4; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Distinguish new onset from worsening of the same symptoms and limit causal interpretation to the verified scope of all B6 products, concomitant medicines and underlying causes.", "current_reports": [ "S11", "S12", "S13" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The manuscript records the need to separately examine overlapping use of multiple B6 products, drug interactions and total intake. Analgesic efficacy was not inferred from low B6 markers alone; actual participants' total exposure and alternative causes remain unverified.", "condition_status": "Partly verified", "status_reason": "The need to examine total exposure and alternative causes, and official context, are available, but there are no product, medication or alternative-cause data for individual trial participants.", "missingness": "Gaps in actual total exposure, concurrent treatment and alternative causes for each participant.", "uncertainty": "Gaps in actual total exposure, concurrent treatment and alternative causes for each participant.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "A complete product list and ingredient/schedule details, concomitant medicines, neuropathy diagnoses and symptom timing records." }, { "item_id": "N34", "question_type": "Upper limits and regulatory timing", "question": "Can current official nutritional upper limits, the scope of preparations and implementation status be verified?", "needed": "Sources and populations for US/EFSA nutritional upper limits, the Australian scope of preparations, effective dates and the original cutoff date.", "role": "Supplementary; essential for nutritional and regulatory interpretation", "role_reason": "Timing and the nature of each figure must be distinguished so that upper limits or regulatory figures are not misread as doses with verified efficacy or thresholds of no risk.", "application_exception": "No new checks of legislation or official websites are performed in this review. Do not describe a historical planned date as current implementation.", "criterion": "Distinguish the different nutritional and regulatory information at the original cutoff date; do not use it as an effective pain-treatment dose, a safe dose or verification of current law.", "basis": "M04 §4.5, §4.6.3; limits on the current data conversion follow the user-defined scope and custom design / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M19 §19.1.2–19.2.4; custom application / Chamgap's own interpretation limits. M19 principles are referenced; no official causality tool was applied", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "When updating official information, verify legislation, nutritional standards and treatment effects separately while retaining the original cutoff-date record.", "current_reports": [ "S12", "S13", "S14" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The manuscript records US FNB 100 mg/day for adults and EFSA 12 mg/day for adults as different nutritional upper limits. Australia's transition to pharmacist-only control for preparations above 50 mg~up to and including 200 mg/day is scheduled for 2027-06-01 and was not yet in force at the original cutoff date.", "condition_status": "Partly verified", "status_reason": "The original figures, populations and planned effective date were verified in the retained input, but external official documents and any current changes were neither read nor checked in this review.", "missingness": "Current official regulatory/nutritional documents were not rechecked in this review; no link to a direct pain-treatment dose.", "uncertainty": "Current official regulatory/nutritional documents were not rechecked in this review; no link to a direct pain-treatment dose.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "The latest editions and implementation history of the relevant official documents, and the populations and scope of the original standards." }, { "item_id": "N35", "question_type": "Long-term and vulnerable-group safety", "question": "Are there direct safety data on long-term/rare harms and vulnerable groups?", "needed": "Long-term/rare events in the same population at the actual dose/duration, and exposure in kidney disease, pregnancy and lactation, with denominators/follow-up.", "role": "Supplementary; essential for long-term safety and safety in vulnerable groups", "role_reason": "Needed to avoid extending data from short-term observation or limited populations to overall safety.", "application_exception": "Not every study of rare harms is required as an efficacy condition for the current narrow NRS question. Broader safety claims require direct data.", "criterion": "Do not extend short observations of adjacent efficacy or nutritional upper limits to long-term safety or safety in vulnerable groups.", "basis": "M19 §19.1.2–19.2.4; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Use a design for harm collection and follow-up separate from the efficacy trial, and specify the limitations of the population, duration and denominators. Interpret the absence of rare events only within the scope of complete collection.", "current_reports": [ "S13", "S14" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The manuscript leaves long-term safety unresolved and records that the dose and long-term safety for this pain question in kidney disease, pregnancy and lactation are unverified.", "condition_status": "Unverified", "status_reason": "Long-term and rare events, and exposure, denominators and follow-up in vulnerable groups, could not be verified for the same intervention and pain population.", "missingness": "Gaps in direct data on long-term and rare harms and special populations.", "uncertainty": "Gaps in direct data on long-term and rare harms and special populations.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Harm data with sufficient follow-up, and exposure, events, denominators/duration for each vulnerable group." }, { "item_id": "N36", "question_type": "Material review", "question": "Are the historical access level of each material and the scope actually read on this occasion distinguished?", "needed": "The access_level and location in retained citations/evidence, actual current material types, access/acquisition, reading, dates and safe links.", "role": "Required", "role_reason": "The scope of materials actually read must be recorded accurately so that a blue summary link is not mistaken for verification of the full clinical text.", "application_exception": "The existence of a document or URL does not mean access succeeded. Do not label a full text as inaccessible merely because its public availability could not be verified.", "criterion": "Mark only the local retained summaries read on this occasion as read, and leave external materials as unattempted and unread. If an individual access date is absent, record an empty value.", "basis": "M04 §4.5–4.6 principles for material collection/selection; separation of access from reading and the hyperlink contract are a custom design / M04 §4.5, §4.6.3; limits of the current material conversion follow the user-defined scope and custom design", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "For newly acquired materials, record the sections actually read and dates by material type, and keep retained summaries and full texts as separate items.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S06", "S07", "S08", "S09", "S10", "S11", "S12", "S13", "S14", "S15" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "On this occasion, the KO/EN text and all structures of the retained manuscript matching the current original were read. External abstracts, full texts, official documents and registrations were not newly accessed. Historical full-text access levels for S02/S09/S11–S15 and S04’s historical 403 were not retrospectively treated as current reading or failure.", "condition_status": "Verified", "status_reason": "The scope actually read is separated from external access not attempted/materials not read, and report-specific access dates are empty values because they are absent from the original. The global evidence cutoff of 2026-09-15 was retained separately.", "missingness": "All current external clinical source materials remain unread; report-specific historical access dates are unverified.", "uncertainty": "All current external clinical source materials remain unread; report-specific historical access dates are unverified.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Actual logs of access, acquisition and reading for each material, original locations, and complete source materials where available." }, { "item_id": "N37", "question_type": "Search and preservation scope", "question": "Within which search, date and input scope was the direct result not verified?", "needed": "The original evidence cutoff and documented scope of search, selection and access, the files actually read now, and unacquired logs/registrations.", "role": "Required", "role_reason": "The dates and inputs underlying statements of absence must be limited so that material conversion is not overstated as an up-to-date comprehensive literature review.", "application_exception": "Incomplete searching or registry access is not evidence that no studies exist. Do not assume that the contents of a separate file have been read now.", "criterion": "Explain what remains unverified within the checked scope, and do not extend the absence of a new search or historical access limitations into a claim of 0 studies or worldwide absence of literature.", "basis": "M04 §4.5, §4.6.3; limits of the current material conversion follow the user-defined scope and custom design / M04 §4.5–4.6 principles for material collection/selection; separation of access from reading and the hyperlink contract are a custom design / M08 Table 8.2.a, M04 §4.6.3; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "In future evidence updates, record the actual search queries, dates, selection reasons and access failures, and link them to the current table as a separate version.", "current_reports": [ "S03", "S04", "S08", "S15" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The evidence cutoff is 2026-09-15, and the review date recorded for this conversion is 2026-10-05. The manuscript refers to historical search records, url_access_log.json, selection_log.json and an old ZIP, but those files were not opened on that occasion. Only the currently retained summaries were converted.", "condition_status": "Partly verified", "status_reason": "The dates, documented search scope and limitations of the manuscript were checked, but separate logs, the old ZIP and the complete scope of unpublished studies/registrations were not rechecked now.", "missingness": "No current new search, reading of separate logs, or verification of the completeness of registrations/corrections was performed.", "uncertainty": "No current new search, reading of separate logs, or verification of the completeness of registrations/corrections was performed.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "The original search, selection and access logs, and future updated registration, correction and result records." }, { "item_id": "N38", "question_type": "Preservation of the original judgment", "question": "Are the original ?, empty values, B/P and the limited meaning of no_human_study preserved?", "needed": "The original grade, score, axes, strengths/calculation status, and endpoint-scoped interpretation of no_human_study.", "role": "Required", "role_reason": "The historical judgment must be distinguished from the data-verification status in the table so that empty values are not changed into a score of 0 or an absence of effect.", "application_exception": "Do not run the original calculator or recalculate the grade. Do not isolate the no_human_study label and interpret it as an absence of all research.", "criterion": "Preserve the original values exactly, and do not use the B/P question classification as fulfillment of a result condition or a new score. A count of 0 directly eligible results does not mean 0 human studies or an effect of 0.", "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are a custom design / M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of results to each question is a custom design / M04 §4.5, §4.6.3; limits of the current material conversion follow the user-defined scope and custom design", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "When eligible evidence is updated, first compare the material identity and endpoints. Do not add the statuses in this table to the existing calculator score.", "current_reports": [], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "Record from the preservation-table review dated 2026-10-05: The original grade is ?, and the score, the remaining five axes and the strength count are empty values. B/P classify the question as clinical efficacy/a patient-reported endpoint. no_human_study true has the narrow meaning that directly eligible mean NRS results are unverified; it does not deny the existence of human B6 research itself.", "condition_status": "Verified", "status_reason": "The original values and the explicit explanation of scope were preserved together. No new grading, scoring or judgment of effect was performed.", "missingness": "Original unscored/empty values and the direct NRS gap retained; no new judgment.", "uncertainty": "Original unscored/empty values and the direct NRS gap retained; no new judgment.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "A separate record of approved evidence, calculations, version and reasons for change if the original judgment is changed." }, { "item_id": "N39", "question_type": "Independent replication", "question": "Can independent replication of directly eligible monotherapy NRS studies be verified?", "needed": "Unique trials/report families, direct NRS results, denominators, institutions, funding and differences in conditions.", "role": "Required", "role_reason": "The existence of material families and independent replication of monotherapy NRS results are different facts.", "application_exception": "Do not replace unverified eligible families with NA for between-study comparison. Preserve both the existence of human studies and the count of directly verified results.", "criterion": "Do not use the number of reports, the 7 adjacent families or reviews as the number of directly eligible studies or as independent replication.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; linking cohorts/results is a custom application / Chamgap’s own independence and attribution conditions. The official methods sections used for this pilot do not warrant every detail of this item / M04 §4.6.1–4.6.2, M15 §15.3.1; custom application", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "After linking reports from the same trial, compare the conditions and directions of actual unique eligible results, and leave unverified study/participant counts as empty values.", "current_reports": [ "S01", "S02", "S03", "S04", "S15" ], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The original record has a verified_eligible_mean_NRS_result_count of 0, but adjacent human B6 studies exist. Unverified McCann/Cohen reports and ineligible families were not combined to create a direct NRS replication count or an independent participant count.", "condition_status": "Unverified", "status_reason": "Unique eligible NRS results and independent institutions/funding have not been verified, so replication counts and consistency cannot be assessed. The recorded 0 is limited to the count of results verified at that time for the fixed question.", "missingness": "Gaps in unique eligible trials, independence and the distribution of direct results.", "uncertainty": "Gaps in unique eligible trials, independence and the distribution of direct results.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Eligible NRS results by family and a table of institutions, funding and report relationships." }, { "item_id": "N40", "question_type": "Extension to other clinical outcomes", "question": "Does the pain NRS question require outcomes of neural recovery, disease prevention or mortality?", "needed": "Separate outcome definitions for mean pain and for nerve conduction, PLP, blood glucose, function and disease events.", "role": "Supplementary; essential for extended claims", "role_reason": "Needed to avoid unnecessarily requiring other clinical endpoints for the narrow pain question or extending numerical improvement to effects on clinical events.", "application_exception": "Do not reuse this NA for a claim about another clinical effect. Keep harm conditions separate.", "criterion": "The current independent question concerns mean pain NRS, so other clinical events are not imposed as essential conditions for fulfilling that question. Extended claims require separate direct data.", "basis": "M03 §3.2.4; custom boundary on extension / M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are a custom design / M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of results to each question is a custom design", "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification", "proposed_research": "Design pain scores and neural function/disease events as different questions, and verify each endpoint, duration and denominator independently.", "current_reports": [], "existence": "The relevant passages of the preserved current source summaries were actually read. External materials remain unattempted/unread for each report", "acquired_read": "The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review", "observation": "The current judgment concerns a reduction in mean pain NRS. Nerve conduction, PLP, fasting glucose and general symptoms do not substitute for this result, and the table does not establish separate effects on neural recovery, disease prevention or mortality.", "condition_status": "Not applicable", "status_reason": "Other clinical events are not required endpoints of the fixed NRS question. Not applicable is not a substitute status for unread external full texts or safety gaps.", "missingness": "Effects extending beyond the current question remain a separate unverified scope.", "uncertainty": "Effects extending beyond the current question remain a separate unverified scope.", "review_date": "2026-10-05", "reading_status": "Original material unread in this review · Retained summary read", "additional_material": "Direct reports on the relevant event or functional outcome if an extended claim is made." } ], "reports": [ { "report_id": "S01", "title": "The influence of pyridoxine in diabetic peripheral neuropathy", "url": "https://pubmed.ncbi.nlm.nih.gov/6751736/", "report_type": "PubMed bibliographic record and abstract", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "TF-LEVIN-1981", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "18 participants, symptom-category denominators of 9/9, and substantial improvement in pain or paresthesia in 6/9 versus 4/9. The mean NRS effect and CI are unverified.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed bibliographic record and abstract", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: primary_abstract. Abstract; Diabetes Care 4(6):606-609 This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S01-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/6751736/", "parent_url": null }, { "material_type": "Full text of the original article", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "The direct full-text URL, public availability, acquisition and reading are unverified/not attempted on this occasion. A separate bibliographic link does not establish verification of the full text, and the abstract/author-provided public access level of M1 is not copied to this material. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: primary_abstract. Abstract; Diabetes Care 4(6):606-609 This record does not mean that the external source material was acquired or its full text read on this occasion.", "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": "Author-provided public full text of the article", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "TF-LEVIN-1981", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "Pharmacy randomization, double blinding, a visually matching placebo, instructions to maintain diet/medications, and supply by Hoffman LaRoche. The study used its own −1/0/+1/+2 categories, not NRS.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Author-provided public full text of the article", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: author_deposited_full_text_html. pp606-607 Subjects and Methods; Study protocol; p607 Results/Symptoms; p608 Discussion. Web text lines199-263,323-365,395-437,615-655 This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S02-M1", "url": "https://www.researchgate.net/publication/16446742_The_Influence_of_Pyridoxine_in_Diabetic_Peripheral_Neuropathy", "parent_url": null }, { "material_type": "Full text of the original article", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "The direct full-text URL, public availability, acquisition and reading are unverified/not attempted on this occasion. A separate bibliographic link does not establish verification of the full text, and the abstract/author-provided public access level of M1 is not copied to this material. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: author_deposited_full_text_html. pp606-607 Subjects and Methods; Study protocol; p607 Results/Symptoms; p608 Discussion. Web text lines199-263,323-365,395-437,615-655 This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S02-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.researchgate.net/publication/16446742_The_Influence_of_Pyridoxine_in_Diabetic_Peripheral_Neuropathy" } ] }, { "report_id": "S03", "title": "Pyridoxine and diabetic neuropathy: a double-blind controlled study", "url": "https://pubmed.ncbi.nlm.nih.gov/6341012/", "report_type": "PubMed bibliographic document (abstract unverified)", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "TF-MCCANN-1983", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "The title describes a double-blind controlled study, but the pain instrument, dose/schedule, original results and denominators are unverified. S15 is a discovery lead, and S17 is absent from the current list.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed bibliographic document (abstract unverified)", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: metadata_no_abstract. PubMed bibliographic entry and publication types; Diabetes Care 6(1):102-103 This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S03-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/6341012/", "parent_url": null }, { "material_type": "Full text of the original article", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "The direct full-text URL, public availability, acquisition and reading are unverified/not attempted on this occasion. A separate bibliographic link does not establish verification of the full text, and the abstract/author-provided public access level of M1 is not copied to this material. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: metadata_no_abstract. PubMed bibliographic entry and publication types; Diabetes Care 6(1):102-103 This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S03-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/6341012/" } ] }, { "report_id": "S04", "title": "Effect of pyridoxine (vitamin B6) on diabetic patients with peripheral neuropathy", "url": "https://pubmed.ncbi.nlm.nih.gov/6381578/", "report_type": "PubMed bibliographic document (abstract unverified)", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "TF-COHEN-1984", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "Only a clinical-trial index entry is available; the pain instrument, time point, original results and denominators are unverified. Historical access failure is not used as a finding of no effect.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed bibliographic document (abstract unverified)", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: metadata_no_abstract. PubMed record; J Am Podiatry Assoc 74(8):394-397 This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S04-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/6381578/", "parent_url": null }, { "material_type": "Full text of the original article", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "The direct full-text URL, public availability, acquisition and reading are unverified/not attempted on this occasion. A separate bibliographic link does not establish verification of the full text, and the abstract/author-provided public access level of M1 is not copied to this material. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: metadata_no_abstract. PubMed record; J Am Podiatry Assoc 74(8):394-397 This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S04-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/6381578/" } ] }, { "report_id": "S05", "title": "Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial", "url": "https://pubmed.ncbi.nlm.nih.gov/23218892/", "report_type": "PubMed bibliographic record and abstract", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "TF-METANX-2013", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "A PLP/folate/B12 combination. The primary outcome was vibration perception threshold and the secondary outcome was NTSS-6; favorable secondary findings are not attributed to a mean NRS effect of B6 alone.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed bibliographic record and abstract", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: primary_abstract. Purpose; Research design and methods; Results; Trial registration This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S05-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/23218892/", "parent_url": null }, { "material_type": "Full text of the original article", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "The direct full-text URL, public availability, acquisition and reading are unverified/not attempted on this occasion. A separate bibliographic link does not establish verification of the full text, and the abstract/author-provided public access level of M1 is not copied to this material. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: primary_abstract. Purpose; Research design and methods; Results; Trial registration This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S05-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/23218892/" } ] }, { "report_id": "S06", "title": "Impact of Pyridoxine Supplement on Oxidative Stress in Type 2 Diabetic Patients", "url": "https://ajps.uomustansiriyah.edu.iq/index.php/AJPS/article/view/1030", "report_type": "Publisher bibliographic record and abstract", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "TF-DAWOOD-2024", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "Metabolic and oxidative-stress results related to newly diagnosed T2DM/metformin, not used as mean NRS results for painful DSPN.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Publisher bibliographic record and abstract", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: Publisher abstract. Abstract: study objective, arms and oxidative stress results This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S06-M1", "url": "https://ajps.uomustansiriyah.edu.iq/index.php/AJPS/article/view/1030", "parent_url": null }, { "material_type": "Full text of the original article", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "The direct full-text URL, public availability, acquisition and reading are unverified/not attempted on this occasion. A separate bibliographic link does not establish verification of the full text, and the abstract/author-provided public access level of M1 is not copied to this material. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: Publisher abstract. Abstract: study objective, arms and oxidative stress results This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S06-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://ajps.uomustansiriyah.edu.iq/index.php/AJPS/article/view/1030" } ] }, { "report_id": "S07", "title": "Pyridoxine in the Treatment of Peripheral Nerve Related Foot Pain", "url": "https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART001802154", "report_type": "Publisher-supplied abstract in an official index", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "TF-BAE-2013", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "A report of improvement in retrospective, uncontrolled, heterogeneous foot pain. Not used as an estimate of mean NRS versus placebo in diabetic pain.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Publisher-supplied abstract in an official index", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: publisher_supplied_abstract_in_official_index. Abstract Materials/Methods; 2013 vol17(3):203-208; authors Bae, Jung, Oh This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S07-M1", "url": "https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART001802154", "parent_url": null }, { "material_type": "Full text of the original article", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "The direct full-text URL, public availability, acquisition and reading are unverified/not attempted on this occasion. A separate bibliographic link does not establish verification of the full text, and the abstract/author-provided public access level of M1 is not copied to this material. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: publisher_supplied_abstract_in_official_index. Abstract Materials/Methods; 2013 vol17(3):203-208; authors Bae, Jung, Oh This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S07-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART001802154" } ] }, { "report_id": "S08", "title": "The Benefits of Vitamin B Combination as Add on Therapy", "url": "https://clinicaltrials.gov/study/NCT04689971", "report_type": "Official registry index and application shell", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "TF-NCT04689971", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "A limited index record of B1/B6/B12 add-on therapy. The latest status, actual results and denominators are unverified, and this is not B6 alone.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Official registry index and application shell", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: official_registry_indexed_excerpt_and_shell. Indexed study description: B1/B6/B12 added to standard treatment; direct page rendered application shell This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S08-M1", "url": "https://clinicaltrials.gov/study/NCT04689971", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT04689971" } ] }, { "report_id": "S09", "title": "12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes—2026", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12690177/", "report_type": "Full text of the clinical practice guideline", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "CONTEXT-ADA-2026", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "Clinical-care context for painful neuropathy. Absence of B6 from the recommendations is not used to infer an effect of 0 or to change the efficacy score.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the clinical practice guideline", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: Full-text article HTML. Neuropathy; Treatment recommendations 12.21 and 12.22; Neuropathic Pain Management This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S09-M1", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12690177/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12690177/" } ] }, { "report_id": "S10", "title": "Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update Summary", "url": "https://pubmed.ncbi.nlm.nih.gov/34965987/", "report_type": "PubMed bibliographic record and abstract", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "CONTEXT-AAN-2022", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "Clinical-care context for painful diabetic polyneuropathy; the absence of a B6 recommendation is not treated as a finding of no effect.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed bibliographic record and abstract", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: primary_guideline_abstract. Abstract Recommendations summary This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S10-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/34965987/", "parent_url": null }, { "material_type": "Full text of the original article", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "The direct full-text URL, public availability, acquisition and reading are unverified/not attempted on this occasion. A separate bibliographic link does not establish verification of the full text, and the abstract/author-provided public access level of M1 is not copied to this material. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: primary_guideline_abstract. Abstract Recommendations summary This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S10-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/34965987/" } ] }, { "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": "Full text of an official web document", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "SAFETY-TGA-B6", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "Possible peripheral/sensory neuropathy associated with B6 supplementation; risk below 50 mg/day or with multiple products cannot be excluded. The minimum dose/duration associated with that risk is unverified, and recovery is not guaranteed.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of an official web document", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: official_full_html. Summary; What health professionals should do; background; published 2022-10-04, updated 2026-02-25 This record does not mean that the external source material was acquired or its full text read on this occasion.", "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": "Full text of an official web document", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "SAFETY-TGA-B6", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "The change to pharmacist supervision for preparations above 50 mg~up to and including 200 mg/day was scheduled for 2027-06-01. It had not taken effect at the original cutoff and provides no guarantee of recovery or a safe threshold.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of an official web document", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: official_full_html. Summary and What health professionals should do, lines195-210; published2026-02-19, updated2026-04-07 This record does not mean that the external source material was acquired or its full text read on this occasion.", "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": "Full text of an official web document", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "SAFETY-ODS-B6", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "The US FNB adult upper limit of 100 mg/day is a nutritional standard. Low B6 indices in kidney disease, medicine interactions and total intake are not used as direct evidence of an effect on pain.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of an official web document", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: official_full_html. Introduction; Individuals with Impaired Renal Function; Health Risks; Table3; Interactions with Medications This record does not mean that the external source material was acquired or its full text read on this occasion.", "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": "Full text of an official risk-assessment report", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "SAFETY-EFSA-B6", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "EFSA adult upper limit of 12 mg/day (the source scope includes pregnancy and lactation). It does not substitute for the dose or long-term safety for this pain question.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of an official risk-assessment report", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: official_full_html. Summary/conclusions: adult UL including pregnancy and lactation This record does not mean that the external source material was acquired or its full text read on this occasion.", "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": "S15", "title": "Association between neuropathy and B-vitamins: A systematic review and meta-analysis", "url": "https://onlinelibrary.wiley.com/doi/full/10.1111/ene.14786", "report_type": "Full text of a review article", "existence": "A reference from retained bibliographic and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the retained manuscript were read. The linked external source materials were not read on this occasion.", "study_family": "TF-MCCANN-1983", "independent_replication": "Unverified; the number of reports is not the number of independent clinical studies", "observed_result": "A review reference used to identify the McCann candidate. Review-level values are not counted as verified original results or an independent trial.", "result_level": "Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of a review article", "public_status": "Current public availability unverified; existence/links are limited to the original retained bibliographic records", "access_status": "Access not attempted on this occasion", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This external material was not opened on this occasion. What was actually read now was the corresponding citation/evidence and main-text summary in the retained manuscript; the original access level is a historical record. Historical access dates for individual materials are unverified. The retained manuscript review date of 2026-09-15 is not the access date of the source file. Historical material-type record: review_full_text_html. Reference63 McCann1983 and intervention summary; references of B-vitamin studies This record does not mean that the external source material was acquired or its full text read on this occasion.", "material_id": "S15-M1", "url": "https://onlinelibrary.wiley.com/doi/full/10.1111/ene.14786", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://onlinelibrary.wiley.com/doi/full/10.1111/ene.14786" } ] } ], "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility criteria and reasons for changes, and distinguish variations of the intervention.", "review_level": "The retained record describes reuse of byte copies and SHA values of the original methods texts retained for the 1585 pilot. No new web/full methods-text reading or execution of the complete official tools was performed in that recorded review" }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish and link studies and reports, and do not omit studies solely because results are unreported.", "review_level": "The retained record describes reuse of byte copies and SHA values of the original methods texts retained for the 1585 pilot. No new web/full methods-text reading or execution of the complete official tools was performed in that recorded review" }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Fix the outcome and effect of interest, and examine randomization, deviations, missingness, measurement and selective reporting.", "review_level": "The retained record describes reuse of byte copies and SHA values of the original methods texts retained for the 1585 pilot. No new web/full methods-text reading or execution of the complete official tools was performed in that recorded review" }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "The retained record describes reuse of byte copies and SHA values of the original methods texts retained for the 1585 pilot. No new web/full methods-text reading or execution of the complete official tools was performed in that recorded review" }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require designs, populations and follow-up different from those for efficacy. Case reports do not establish incidence rates.", "review_level": "The retained record describes reuse of byte copies and SHA values of the original methods texts retained for the 1585 pilot. No new web/full methods-text reading or execution of the complete official tools was performed in that recorded review" } ], "status_dictionary": { "Verified": "The question within the specified retained materials and scope is verified; this does not establish efficacy or safety", "Partly verified": "Only some actual data have been verified, and the full condition remains unverified", "Unverified": "Direct data, methods or results could not be verified within the relevant scope; this does not mean no effect or no research", "Not met": "The actual intervention, population, endpoint/comparator in currently known materials does not match the fixed question; this is not a judgment of clinical ineffectiveness", "Not applicable": "An extension condition that does not apply to the current narrow question; not a substitute for external materials not read" }, "study_overlap": { "state": "Report and family counts record existence. The 15 reports and 7 families are not converted into a count of direct NRS trials or independent replications. The Levin abstract and author-provided full text concern the same study, and S17 in the McCann linkage is absent from the current source list, so its identity is unverified. S01, S02: study-specific symptom-change categories, not validated mean pain NRS / S03, S15, S17: full text, pain scale and results unverified / S04: historical full-text access failure; pain scale and results unverified / S05: a PLP/folate/B12 combination, so attribution to B6 alone is not possible. Primary vibration perception threshold and secondary NTSS-6 are not mean NRS / S06: metabolic/oxidative-stress endpoints, not pain NRS / S07: an uncontrolled heterogeneous foot-pain group; not a between-group result for diabetic pain / S08: a B1/B6/B12 combination registration; not B6 alone", "unique_trial_count": null, "unique_participant_count": null, "reason": "Report and family counts record existence. The 15 reports and 7 families are not converted into a count of direct NRS trials or independent replications. The Levin abstract and author-provided full text concern the same study, and S17 in the McCann linkage is absent from the current source list, so its identity is unverified. S01, S02: study-specific symptom-change categories, not validated mean pain NRS / S03, S15, S17: full text, pain scale and results unverified / S04: historical full-text access failure; pain scale and results unverified / S05: a PLP/folate/B12 combination, so attribution to B6 alone is not possible. Primary vibration perception threshold and secondary NTSS-6 are not mean NRS / S06: metabolic/oxidative-stress endpoints, not pain NRS / S07: an uncontrolled heterogeneous foot-pain group; not a between-group result for diabetic pain / S08: a B1/B6/B12 combination registration; not B6 alone" }, "history": [ { "date": "2026-11-02", "kind": "Separation of the public display and materials", "view_version": "1.0", "change": "The public display and materials were created from the existing 40 items. No new clinical search, change in verification status or scoring was performed." } ], "language": "en", "translation_date": "2026-11-02" }