Vitamin B6: pyridoxine hydrochloride × Lower mean pain NRS in painful diabetic distal symmetric polyneuropathy

Required evidence, verification status and materials actually read
Item	AVerification status	BReading scope	CReview item	DCurrent findings	EWhy unverified	FRequired materials and conditions	GFurther research
1	Verified	Full text not readStored summary read	N01 · Claim boundariesWhich population, intervention, comparator and pain outcome are being examined as a single question?Required	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. S01 S02 S03 S04	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.	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.	First screen studies that retain this question, and extract combinations, deficiency correction and other endpoints separately.
2	Partly verified	Full text not readStored summary read	N02 · Ingredient and formulationDo the actual study ingredient, route and formulation match the question about pyridoxine hydrochloride alone?Required	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. S01 S02 S05 S13	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.	The vitamer, salt and all active ingredients; oral route; and tablet release type, purity, batch and manufacturing origin.	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.
3	Partly verified	Full text not readStored summary read	N03 · Participant diagnosisWere participants selected as having painful diabetic DSPN?Required	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. S01 S02 S03 S04	Information on diabetes and a symptomatic population is available, but direct eligibility in terms of pain diagnosis, selection procedures and baseline pain is unverified.	Diagnostic and selection criteria for diabetes, distal symmetric neuropathy and pain; age, baseline pain and exclusion criteria.	Define diabetic distal symmetric neuropathy and pain in advance, and separate results for other neuropathies and populations treated to correct deficiency.
4	Unverified	Full text not readStored summary read	N04 · Deficiency and special populationsAre data available to distinguish correction of B6 deficiency from the separate questions concerning kidney disease, pregnancy and lactation?Supplementary; required for extension to those populations	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. S13 S14	The preserved inputs contain no direct NRS results by population stratum or information on deficiency assessment and inclusion of special populations.	Assessment of baseline deficiency and participants by stratum; inclusion of participants by kidney function, pregnancy and lactation; and direct pain estimates.	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.
5	Partly verified	Full text not readStored summary read	N05 · Common background careAre the actual comparator groups’ background care and placebo contents verified?Required	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. S02 S03 S04	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.	Investigational-product and placebo composition; diet, medication, analgesics and rescue medication in both groups; and records of changes.	Define background care in both groups and record medication changes and rescue use, linking them to interpretation of assignment and adherence effects.
6	Partly verified	Full text not readStored summary read	N06 · DoseAre the actual dose and administration schedule for an eligible mean NRS comparison verified?Required	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. S01 S02 S03 S04	The adjacent dose schedule is preserved, but an eligible dose used to assess NRS efficacy and actual total exposure have not been verified.	The connection between actual dose, frequency, total B6 exposure and the corresponding NRS result; identification of totals derived from historical schedules.	Link a verified monotherapy dose only to its study results. Review claims about an optimal dose separately, only when direct dose comparisons are available.
7	Partly verified	Full text not readStored summary read	N07 · Observation periodAre the measurement time point, treatment duration and post-discontinuation follow-up for eligible NRS results verified?Required	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. S01 S02 S03 S04	The adjacent duration is verified, but it cannot be directly linked to mean NRS at the same time point or to sustained effects.	Actual NRS collection time points; treatment, follow-up and discontinuation periods; and separate results on sustained effects.	Prespecify the NRS assessment window and end time point, and examine sustained effects through separate estimates after treatment ends.
8	Unverified	Full text not readStored summary read	N08 · Pain scaleDid an actual eligible study use a validated mean pain NRS?Required	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. S01 S02 S03 S04	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.	Scale name, range, direction and validity; collection procedures and time points; and the definition of mean pain.	Prespecify the validated NRS, collection window and direction, and report mixed pain-or-paresthesia categories separately.
9	Not met	Full text not readStored summary read	N09 · Categorical scaleAre Levin’s −1/0/+1/+2 categories eligible as direct mean NRS results?Required	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. S01 S02	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.	The meaning of the original symptom categories, their pain/paresthesia composition and measurement differences from NRS.	Extract ordinal categories using their original definitions and check whether direct NRS results were reported separately. Do not invent means or standard deviations.
10	Not met	Full text not readStored summary read	N10 · Responder countsDo 6/9 versus 4/9 represent mean NRS or a 50% pain-response rate?Required	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. S01 S02	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.	The original response definition, pain/paresthesia composition, denominator for each response and distinction from mean pain outcomes.	Report mean pain and prespecified response measures separately, linking each result to its denominator.
11	Partly verified	Full text not readStored summary read	N11 · Participant flowCan the denominators for allocation, symptom response, completion, and NRS analysis be distinguished?Required	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. S01 S02	Allocation and categorical-response denominators are verified, but denominators for completion, visits, and direct NRS analysis are unverified.	Allocation and participant flow by group, symptom-response denominators, visit completion, and counts measured and analyzed for NRS.	Extract allocation, measurement, completion, and analysis denominators for each endpoint/visit, without using them interchangeably.
12	Unverified	Full text not readStored summary read	N12 · Mean pain valuesCan baseline, change, and endpoint mean NRS values be directly verified?Required	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. S01 S02 S03 S04	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.	Group-specific baseline, change, and endpoint NRS means, units, time points, and analysis populations.	Extract baseline, change, and endpoint values separately and specify in advance the between-group effect to be estimated.
13	Unverified	Full text not readStored summary read	N13 · Variance and errorAre the SD, SE, sample size, and type of error statistic for direct NRS results verified?Required	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. S01 S02 S03 S04	Without material verifying direct NRS variance and the type of error statistic, the inputs needed to judge precision cannot be linked.	Group-specific variances for NRS changes/endpoint values, the SD/SE labels and n, and covariance and model descriptions where needed.	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.
14	Unverified	Full text not readStored summary read	N14 · Between-group estimationAre the between-group difference, CI, P value, and effect of interest for the fixed NRS question verified?Required	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. S01 S02 S03 S04	Without an analysis population, model, or direct NRS estimate, the direction, magnitude, and interval of the between-group effect cannot be verified.	Effects of assignment/adherence, the model, direction, CI, P value, and analysis denominator for the difference in changes or endpoint values.	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.
15	Unverified	Full text not readStored summary read	N15 · Clinical importanceIs there an applicable threshold for an important difference with which to interpret the direct NRS effect?Required	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. S01 S02 S03 S04	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.	An MCID or justified important difference for the same population, scale, and assessment window, together with the interval for the direct effect.	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.
16	Partly verified	Full text not readStored summary read	N16 · Allocation and designCan actual allocation, concealment, and baseline balance be verified?Required	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. S02 S03 S04	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.	Parallel/crossover/cluster structure, random-sequence generation and allocation-concealment procedures, and baseline characteristics by group.	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.
17	Partly verified	Full text not readStored summary read	N17 · Assessment blindingAre blinding and collection procedures for subjective pain assessment verified?Required	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. S02 S03 S04	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.	Blinding of participants, care providers, and assessors; placebo appearance; NRS collection methods; and differences in measurement between groups.	Specify the NRS collection window, who collects it, handling of omissions, and identical procedures across groups, and examine actual limitations in blinding.
18	Unverified	Full text not readStored summary read	N18 · Adherence and rescue medicationCan actual adherence, analgesics, rescue medication, and treatment changes be verified?Required	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. S02 S03 S04	The current input does not verify the numbers or methods concerning actual adherence, concomitant treatment, rescue use, or their effects on group-specific analyses.	Actual intake and adherence by group, concomitant analgesics, rescue medication, treatment changes, and their handling in the analysis.	Distinguish the effect of assignment from the effect of adherence, and report and analyze rescue medication and treatment changes in a prespecified manner.
19	Unverified	Full text not readStored summary read	N19 · Missing data and analysis populationsAre NRS missingness, dropouts, and the actual analysis populations and handling verified?Required	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. S01 S02 S03 S04	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.	Reasons for missing NRS data and dropouts at each visit, ITT/PP, analysis n, handling of missing data, and sensitivity analyses.	Extract endpoint-specific missingness and reasons by group, and prespecify analysis and sensitivity methods appropriate to the effect of interest.
20	Unverified	Full text not readStored summary read	N20 · Plans and selective reportingCan prespecified pain endpoints, analyses, and time points be compared with actual reporting?Required	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. S02 S03 S04 S05 S08	Materials comparing plans with results for direct monotherapy NRS candidates have not been obtained, so whether selective reporting occurred cannot be verified.	Registrations, protocols, and analysis plans for monotherapy candidates; pain-endpoint hierarchy, time points, multiplicity, and reasons for changes.	Compare prespecified pain endpoints, analyses, and time points with actual results, and separately record reasons for changes and multiple comparisons.
21	Unverified	Full text not readStored summary read	N21 · McCann candidateCan the monotherapy, comparator, pain scale, and results of McCann 1983 be directly verified?Required	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. S03 S15	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.	The original article's methods, formulation/dose, comparator, population, pain instrument, and results/denominators, and their agreement with the review's citation.	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.
22	Unverified	Full text not readStored summary read	N22 · Cohen candidateCan the pain instrument, comparator, and direct results of Cohen 1984 be verified?Required	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. S04	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.	The original article's population, single-ingredient composition, design, pain instrument/time point, denominators, and results, together with the actual access history.	After obtaining the original text, screen the single ingredient, population, comparator, and scale, and link only the pain results that can actually be verified.
23	Partly verified	Full text not readStored summary read	N23 · Study families and missing identitiesAre all links between reports and actual study families verified?Required	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. S01 S02 S03 S15	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.	Correspondence between report IDs, DOI/PMID, families, and the original material list, and the identity of missing references.	Link report→study family→endpoint/timepoint/analysis, and manage missing IDs as provisional references until verified.
24	Not met	Full text not readStored summary read	N24 · Metanx combinationDoes Metanx provide a direct comparison of mean NRS for pyridoxine hydrochloride alone?Required	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. S05	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.	Full PLP/folate/B12 composition, primary VPT/secondary NTSS-6, and results isolating the B6 contribution.	Retain combination results by study family and separately check for monotherapy comparisons or comparisons isolating component contributions.
25	Not met	Full text not readStored summary read	N25 · Metabolic and oxidative markersDo Dawood's metabolic and oxidative-stress results directly answer the painful DSPN NRS question?Required	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. S06	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.	The newly diagnosed T2DM/metformin population, actual pain diagnosis and endpoints, and a comparison of B6 alone.	Extract biomarkers as separate outcomes and verify whether painful DSPN and direct NRS results were actually reported.
26	Not met	Full text not readStored summary read	N26 · Uncontrolled foot painIs Bae's foot-pain improvement an eligible diabetes-specific NRS result versus placebo?Required	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. S07	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.	A separately identified diabetic DSPN population, pain instrument, comparison group, denominator, timepoint and between-group estimate.	Retain mixed-population results within their original scope and check whether separate controlled results exist for the specified population.
27	Partly verified	Full text not readStored summary read	N27 · Registry scopeCan the use of monotherapy, latest status and pain results for NCT04689971 be verified?Required	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. S08	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.	Intervention composition, population, endpoints, status and results in the official registration, together with the extent to which the material has actually been obtained.	Link registration, results and publication reports within study families, distinguishing planned information from actual results.
28	Partly verified	Full text not readStored summary read	N28 · Guideline contextCan a direct NRS effect of B6 alone be verified from the ADA/AAN guidelines?Supplementary; essential for interpreting clinical context	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. S09 S10	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.	The guidelines' actual recommendations and evidence links, and results from the relevant monotherapy pain trials.	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.
29	Unverified	Full text not readStored summary read	N29 · Result direction and conflicting findingsCan the favorable, no-difference and unfavorable directions of unique eligible NRS results be compared together?Required	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. S01 S02 S03 S04 S05 S07	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.	Between-group NRS estimates and intervals from unique eligible trials, and differences in populations, interventions, timepoints and analyses.	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.
30	Partly verified	Full text not readStored summary read	N30 · Product supply and conflicts of interestCan product supply, research funding, author conflicts of interest and independence be verified?Supplementary; essential for claims of independence	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. S02 S05	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.	Supply of the active agent and placebo, full funding, employment, patents, disclosed COI, and links to institutions/study families.	Extract funding, product supply and author relationships from the original text, and review the independence claim and relevance to the results separately.
31	Partly verified	Full text not readStored summary read	N31 · Neuropathy harmsCan harm events, denominators and collection methods be verified for the same exposure and population?Supplementary; essential for interpreting safety	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. S11 S12 S13	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.	Definitions, collection, severity and discontinuations relating to new/worsening sensory neuropathy, plus group-specific counts of people with events, exposure denominators and duration.	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.
32	Unverified	Full text not readStored summary read	N32 · Timing of harms and recoveryCan the minimum dose and duration associated with risk of harm, and recovery after discontinuation, be verified?Supplementary; essential for claims about timing and safety thresholds	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. S11 S12	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.	Timing of exposure initiation, duration, event onset/worsening, discontinuation and recovery, with the relevant population and products.	Extract temporal sequence and the course after discontinuation from individual records; do not extrapolate recovery or thresholds beyond the observation period.
33	Partly verified	Full text not readStored summary read	N33 · Overlapping exposures and causesCan all B6 products, concomitant medicines and other causes of symptom worsening be verified?Supplementary; essential for extensions to causality and individual safety	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. S11 S12 S13	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.	Total exposure by food, supplements/medicines and vitamers, concomitant medicines, underlying disease, and alternative causes of new/worsening symptoms.	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.
34	Partly verified	Full text not readStored summary read	N34 · Upper limits and regulatory timingCan current official nutritional upper limits, the scope of preparations and implementation status be verified?Supplementary; essential for nutritional and regulatory interpretation	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. S12 S13 S14	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.	Sources and populations for US/EFSA nutritional upper limits, the Australian scope of preparations, effective dates and the original cutoff date.	When updating official information, verify legislation, nutritional standards and treatment effects separately while retaining the original cutoff-date record.
35	Unverified	Full text not readStored summary read	N35 · Long-term and vulnerable-group safetyAre there direct safety data on long-term/rare harms and vulnerable groups?Supplementary; essential for long-term safety and safety in vulnerable groups	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. S13 S14	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.	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.	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.
36	Verified	Full text not readStored summary read	N36 · Material reviewAre the historical access level of each material and the scope actually read on this occasion distinguished?Required	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. S01 S02 S03 S04 S05 S06 S07 S08 S09 S10 S11 S12 S13 S14 S15	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.	The access_level and location in retained citations/evidence, actual current material types, access/acquisition, reading, dates and safe links.	For newly acquired materials, record the sections actually read and dates by material type, and keep retained summaries and full texts as separate items.
37	Partly verified	Full text not readStored summary read	N37 · Search and preservation scopeWithin which search, date and input scope was the direct result not verified?Required	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. S03 S04 S08 S15	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.	The original evidence cutoff and documented scope of search, selection and access, the files actually read now, and unacquired logs/registrations.	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.
38	Verified	Full text not readStored summary read	N38 · Preservation of the original judgmentAre the original ?, empty values, B/P and the limited meaning of no_human_study preserved?Required	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.	The original values and the explicit explanation of scope were preserved together. No new grading, scoring or judgment of effect was performed.	The original grade, score, axes, strengths/calculation status, and endpoint-scoped interpretation of no_human_study.	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.
39	Unverified	Full text not readStored summary read	N39 · Independent replicationCan independent replication of directly eligible monotherapy NRS studies be verified?Required	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. S01 S02 S03 S04 S15	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.	Unique trials/report families, direct NRS results, denominators, institutions, funding and differences in conditions.	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.
40	Not applicable	Full text not readStored summary read	N40 · Extension to other clinical outcomesDoes the pain NRS question require outcomes of neural recovery, disease prevention or mortality?Supplementary; essential for extended claims	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.	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.	Separate outcome definitions for mean pain and for nerve conduction, PLP, blood glucose, function and disease events.	Design pain scores and neural function/disease events as different questions, and verify each endpoint, duration and denominator independently.

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40 itemsWhat the statuses mean

Assessment scope

Stored-material review date: 2026-10-05
Original evidence date: 2026-09-15
Scope actually checked: Retained Korean and English manuscripts and case-specific condition and application records. Full papers, supplements, registrations, plans and original data were not read.
What the dates mean: This is the date the retained materials were reviewed, not the date of a search for the latest clinical literature.
Population: Adults with painful diabetic distal symmetric polyneuropathy; distinct from treatment solely to correct B6 deficiency
Ingredient, formulation and route: 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
Measured outcome: 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
Questions outside this scope: 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

Evidence and sources

The links below lead to the sources. A link alone does not mean the original source was read or its latest publication status verified.

S01 · The influence of pyridoxine in diabetic peripheral neuropathy

Source

Material type: PubMed bibliographic record and abstract
Materials actually 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.
Findings recorded in the stored summary: 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.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic record and abstract	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.
Full text of the original article	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S02 · Levin 1981: author-deposited full-text rendering

Source

Material type: Author-provided public full text of the article
Materials actually 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.
Findings recorded in the stored summary: 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.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Author-provided public full text of the article	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.
Full text of the original article	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S03 · Pyridoxine and diabetic neuropathy: a double-blind controlled study

Source

Material type: PubMed bibliographic document (abstract unverified)
Materials actually 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.
Findings recorded in the stored summary: 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.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic document (abstract unverified)	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.
Full text of the original article	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S04 · Effect of pyridoxine (vitamin B6) on diabetic patients with peripheral neuropathy

Source

Material type: PubMed bibliographic document (abstract unverified)
Materials actually 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.
Findings recorded in the stored summary: 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.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic document (abstract unverified)	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.
Full text of the original article	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S05 · Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial

Source

Material type: PubMed bibliographic record and abstract
Materials actually 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.
Findings recorded in the stored summary: 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.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic record and abstract	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.
Full text of the original article	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S06 · Impact of Pyridoxine Supplement on Oxidative Stress in Type 2 Diabetic Patients

Source

Material type: Publisher bibliographic record and abstract
Materials actually 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.
Findings recorded in the stored summary: Metabolic and oxidative-stress results related to newly diagnosed T2DM/metformin, not used as mean NRS results for painful DSPN.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Publisher bibliographic record and abstract	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.
Full text of the original article	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S07 · Pyridoxine in the Treatment of Peripheral Nerve Related Foot Pain

Source

Material type: Publisher-supplied abstract in an official index
Materials actually 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.
Findings recorded in the stored summary: A report of improvement in retrospective, uncontrolled, heterogeneous foot pain. Not used as an estimate of mean NRS versus placebo in diabetic pain.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Publisher-supplied abstract in an official index	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.
Full text of the original article	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S08 · The Benefits of Vitamin B Combination as Add on Therapy

Source

Material type: Official registry index and application shell
Materials actually 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.
Findings recorded in the stored summary: 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.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Official registry index and application shell	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S09 · 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes—2026

Source

Material type: Full text of the clinical practice guideline
Materials actually 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.
Findings recorded in the stored summary: 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.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full text of the clinical practice guideline	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S10 · Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update Summary

Source

Material type: PubMed bibliographic record and abstract
Materials actually 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.
Findings recorded in the stored summary: Clinical-care context for painful diabetic polyneuropathy; the absence of a B6 recommendation is not treated as a finding of no effect.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic record and abstract	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.
Full text of the original article	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S11 · Peripheral neuropathy with supplementary vitamin B6 (pyridoxine)

Source

Material type: Full text of an official web document
Materials actually 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.
Findings recorded in the stored summary: 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.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full text of an official web document	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S12 · Medicines containing vitamin B6 (pyridoxine, pyridoxal or pyridoxamine)

Source

Material type: Full text of an official web document
Materials actually 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.
Findings recorded in the stored summary: 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.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full text of an official web document	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S13 · Vitamin B6: Fact Sheet for Health Professionals

Source

Material type: Full text of an official web document
Materials actually 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.
Findings recorded in the stored summary: 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.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full text of an official web document	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S14 · Scientific opinion on the tolerable upper intake level for vitamin B6

Source

Material type: Full text of an official risk-assessment report
Materials actually 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.
Findings recorded in the stored summary: 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.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full text of an official risk-assessment report	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

S15 · Association between neuropathy and B-vitamins: A systematic review and meta-analysis

Source

Material type: Full text of a review article
Materials actually 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.
Findings recorded in the stored summary: A review reference used to identify the McCann candidate. Review-level values are not counted as verified original results or an independent trial.
Record level: Content recorded in the retained manuscript. This is not the result of a new comparison with external source materials now.
Study overlap and independent replication: Unverified; the number of reports is not the number of independent clinical studies

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full text of a review article	Current public availability unverified; existence/links are limited to the original retained bibliographic records	Access not attempted on this occasion	Not read	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.

Report counts versus independent study counts

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

Review criteria

Version CG-GAP-v3097-main-1.0 · Criteria record date 2026-10-05. These are Chamgap's own application conditions, informed by the referenced methods. They do not constitute official assessment-tool certification or a new efficacy score.

N01 · Which population, intervention, comparator and pain outcome are being examined as a single question?

Required materials and conditions: 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.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Fixing this scope prevents categorical improvement or combination-product results from substituting for the NRS effect of monotherapy.
Referenced methods: 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

N02 · Do the actual study ingredient, route and formulation match the question about pyridoxine hydrochloride alone?

Required materials and conditions: The vitamer, salt and all active ingredients; oral route; and tablet release type, purity, batch and manufacturing origin.
Conditions for verification: Distinguish oral pyridoxine hydrochloride alone from a PLP/B12/folate combination, and link only the formulation actually verified to the relevant study.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Differences in vitamers, salts and combination composition directly affect attribution to a single ingredient.
Referenced methods: 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

N03 · Were participants selected as having painful diabetic DSPN?

Required materials and conditions: Diagnostic and selection criteria for diabetes, distal symmetric neuropathy and pain; age, baseline pain and exclusion criteria.
Conditions for verification: Compare the actual participant diagnoses with the fixed question; do not establish eligibility for painful DSPN solely from the wording symptomatic diabetes.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: A population with symptomatic diabetes cannot automatically be treated as the same eligible population as precisely diagnosed painful DSPN.
Referenced methods: 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

N04 · Are data available to distinguish correction of B6 deficiency from the separate questions concerning kidney disease, pregnancy and lactation?

Required materials and conditions: Assessment of baseline deficiency and participants by stratum; inclusion of participants by kidney function, pregnancy and lactation; and direct pain estimates.
Conditions for verification: Separate treatment solely to correct deficiency from the specified pain-efficacy question, and do not infer an analgesic effect solely from low B6 indices.
Requirement and applicability: Supplementary; required for extension to those populations
Application exceptions: Do not require studies of every special population for the narrow adult NRS question. Direct data are needed for claims extending to those populations.
Why this condition is needed: Differences in baseline nutritional status and safety in special populations limit generalization of the NRS effect of monotherapy.
Referenced methods: 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

N05 · Are the actual comparator groups’ background care and placebo contents verified?

Required materials and conditions: Investigational-product and placebo composition; diet, medication, analgesics and rescue medication in both groups; and records of changes.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: Do not require every treatment change to be identical. Verify the actual effect of interest and how changes were handled in the analysis.
Why this condition is needed: Needed to avoid wrongly attributing differences in concomitant or rescue medication to pyridoxine’s contribution to pain outcomes.
Referenced methods: 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

N06 · Are the actual dose and administration schedule for an eligible mean NRS comparison verified?

Required materials and conditions: The connection between actual dose, frequency, total B6 exposure and the corresponding NRS result; identification of totals derived from historical schedules.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Distinguishing an adjacent schedule from a dose with direct efficacy evidence prevents data conversion from becoming a new prescribing claim.
Referenced methods: 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

N07 · Are the measurement time point, treatment duration and post-discontinuation follow-up for eligible NRS results verified?

Required materials and conditions: Actual NRS collection time points; treatment, follow-up and discontinuation periods; and separate results on sustained effects.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Linking the endpoint to the observation period prevents old categorical observations from being read as sustained NRS effects.
Referenced methods: 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

N08 · Did an actual eligible study use a validated mean pain NRS?

Required materials and conditions: Scale name, range, direction and validity; collection procedures and time points; and the definition of mean pain.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: Do not enter 0–10 as the NRS range actually used. Preserve other scales with their original values and definitions, without automatic conversion.
Why this condition is needed: Without matching scales, responder counts and differences in mean pain cannot be compared as the same outcome.
Referenced methods: 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

N09 · Are Levin’s −1/0/+1/+2 categories eligible as direct mean NRS results?

Required materials and conditions: The meaning of the original symptom categories, their pain/paresthesia composition and measurement differences from NRS.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Separating known ineligible scales prevents them from filling gaps in eligible pain-effect results.
Referenced methods: 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

N10 · Do 6/9 versus 4/9 represent mean NRS or a 50% pain-response rate?

Required materials and conditions: The original response definition, pain/paresthesia composition, denominator for each response and distinction from mean pain outcomes.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Reading responder counts as a mean difference or as a different response criterion misattributes both the effect and the denominator.
Referenced methods: 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

N11 · Can the denominators for allocation, symptom response, completion, and NRS analysis be distinguished?

Required materials and conditions: Allocation and participant flow by group, symptom-response denominators, visit completion, and counts measured and analyzed for NRS.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: Do not state that there were no participants because a denominator is empty. Keep the McCann/Cohen denominators unverified in their separate candidate records.
Why this condition is needed: Needed to avoid transferring a verified sample size to the analysis denominator for an unverified pain outcome.
Referenced methods: 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

N12 · Can baseline, change, and endpoint mean NRS values be directly verified?

Required materials and conditions: Group-specific baseline, change, and endpoint NRS means, units, time points, and analysis populations.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: The lack of available mean values is a key gap that prevents direct evaluation of the pain effect of interest.
Referenced methods: 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

N13 · Are the SD, SE, sample size, and type of error statistic for direct NRS results verified?

Required materials and conditions: Group-specific variances for NRS changes/endpoint values, the SD/SE labels and n, and covariance and model descriptions where needed.
Conditions for verification: Verify the actual type of error statistic, endpoint, time point, and denominator; do not reconstruct unreported variance from categorical responses.
Requirement and applicability: Required
Application exceptions: Do not assign a new low-precision grade solely because variance is unavailable. Do not transfer values from an ineligible scale into NRS variance.
Why this condition is needed: Direct interpretation of significance or CIs is not possible without the original type of error statistic and denominator.
Referenced methods: 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

N14 · Are the between-group difference, CI, P value, and effect of interest for the fixed NRS question verified?

Required materials and conditions: Effects of assignment/adherence, the model, direction, CI, P value, and analysis denominator for the difference in changes or endpoint values.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: A pain-effect estimate versus placebo cannot be constructed from mean values or counts of favorable responses alone.
Referenced methods: 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

N15 · Is there an applicable threshold for an important difference with which to interpret the direct NRS effect?

Required materials and conditions: An MCID or justified important difference for the same population, scale, and assessment window, together with the interval for the direct effect.
Conditions for verification: Compare thresholds supported by actual sources with direct NRS intervals. Do not invent universal minimum participant counts, durations, trial counts, or an arbitrary MCID.
Requirement and applicability: Required
Application exceptions: Do not fill the gap by proposing unsupported numerical thresholds. If no importance threshold is available, retain the manuscript's unverified status.
Why this condition is needed: Significance or participant counts alone cannot establish the clinical meaning of pain improvement.
Referenced methods: M15 §15.3.1–15.3.3; custom application

N16 · Can actual allocation, concealment, and baseline balance be verified?

Required materials and conditions: Parallel/crossover/cluster structure, random-sequence generation and allocation-concealment procedures, and baseline characteristics by group.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Known allocation descriptions must be distinguished from unverified concealment and baseline balance to assess actual comparability.
Referenced methods: M08 §8.1–8.2.3; custom application

N17 · Are blinding and collection procedures for subjective pain assessment verified?

Required materials and conditions: Blinding of participants, care providers, and assessors; placebo appearance; NRS collection methods; and differences in measurement between groups.
Conditions for verification: Distinguish a double-blind description from actual pain-collection procedures, and do not assign successful blinding or absence of measurement bias without evidence.
Requirement and applicability: Required
Application exceptions: Do not treat inability to blind as an automatic failure. A double-blind label does not establish eligibility of direct NRS measurement.
Why this condition is needed: Patient-reported pain must be reviewed in relation to the actual collection and blinding conditions.
Referenced methods: M08 Table 8.2.a, M03 §3.2.4; custom application

N18 · Can actual adherence, analgesics, rescue medication, and treatment changes be verified?

Required materials and conditions: Actual intake and adherence by group, concomitant analgesics, rescue medication, treatment changes, and their handling in the analysis.
Conditions for verification: Distinguish maintenance instructions from actual behavior, and link the handling of changes by group to their impact on the effect of interest.
Requirement and applicability: Required
Application exceptions: Do not require every change to be identical. The current unverified status does not establish nonadherence or unequal treatment.
Why this condition is needed: Deviations from treatment and other pain-relief interventions may explain differences in pain, so they need separate documentation.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; custom application / M08 §8.2.2, M15 §15.3.1; custom application

N19 · Are NRS missingness, dropouts, and the actual analysis populations and handling verified?

Required materials and conditions: Reasons for missing NRS data and dropouts at each visit, ITT/PP, analysis n, handling of missing data, and sensitivity analyses.
Conditions for verification: Verify the original analysis population and endpoint-specific missingness, without inferring NRS ITT populations or completion counts from allocation counts or categorical denominators.
Requirement and applicability: Required
Application exceptions: Do not convert unverified missingness into confirmed attrition bias or 0 dropouts. Also retain the existence of ineligible categorical results.
Why this condition is needed: Missing data and actual analysis counts are directly needed to interpret mean pain estimates.
Referenced methods: 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

N20 · Can prespecified pain endpoints, analyses, and time points be compared with actual reporting?

Required materials and conditions: Registrations, protocols, and analysis plans for monotherapy candidates; pain-endpoint hierarchy, time points, multiplicity, and reasons for changes.
Conditions for verification: Compare only plans and results that have actually been obtained. Do not describe an unavailable plan as proof of nonregistration or selective reporting.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Comparison with actual plans is needed to avoid treating the current results gap as proof of selective reporting.
Referenced methods: 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

N21 · Can the monotherapy, comparator, pain scale, and results of McCann 1983 be directly verified?

Required materials and conditions: The original article's methods, formulation/dose, comparator, population, pain instrument, and results/denominators, and their agreement with the review's citation.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Unverified monotherapy candidates must be retained to describe honestly the scope of the current direct-evidence gap.
Referenced methods: 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

N22 · Can the pain instrument, comparator, and direct results of Cohen 1984 be verified?

Required materials and conditions: The original article's population, single-ingredient composition, design, pain instrument/time point, denominators, and results, together with the actual access history.
Conditions for verification: Do not use PubMed metadata or the publisher403 record from that time as original results. Verify direct NRS eligibility after obtaining the results.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Retain its status as a separate candidate to avoid confusing failed access with negative pain findings.
Referenced methods: 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

N23 · Are all links between reports and actual study families verified?

Required materials and conditions: Correspondence between report IDs, DOI/PMID, families, and the original material list, and the identity of missing references.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Needed to distinguish report counts from study counts and avoid mistaking a missing reference for replicated numerical evidence.
Referenced methods: 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

N24 · Does Metanx provide a direct comparison of mean NRS for pyridoxine hydrochloride alone?

Required materials and conditions: Full PLP/folate/B12 composition, primary VPT/secondary NTSS-6, and results isolating the B6 contribution.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: Do not label results for the combination as showing no effect. Do not convert VPT/NTSS-6 to NRS.
Why this condition is needed: Needed to prevent misattribution to monotherapy while retaining favorable combination results.
Referenced methods: 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

N25 · Do Dawood's metabolic and oxidative-stress results directly answer the painful DSPN NRS question?

Required materials and conditions: The newly diagnosed T2DM/metformin population, actual pain diagnosis and endpoints, and a comparison of B6 alone.
Conditions for verification: Do not substitute oxidative-stress or metabolic results for the same pain outcome; verify alignment of the actual population, intervention and NRS.
Requirement and applicability: Required
Application exceptions: Do not erase the significance of the verified metabolic study. Do not conclude that other results are absent from an unread original.
Why this condition is needed: Shared references to diabetes and vitamins alone do not justify treating metabolic markers as patient-reported pain outcomes.
Referenced methods: 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

N26 · Is Bae's foot-pain improvement an eligible diabetes-specific NRS result versus placebo?

Required materials and conditions: A separately identified diabetic DSPN population, pain instrument, comparison group, denominator, timepoint and between-group estimate.
Conditions for verification: Do not treat uncontrolled improvement in a mixed population as a control-adjusted effect; verify that the specified population and actual comparison align.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: Before-and-after improvement and an effect versus placebo are different estimates, so the actual study design must be verified.
Referenced methods: 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

N27 · Can the use of monotherapy, latest status and pain results for NCT04689971 be verified?

Required materials and conditions: Intervention composition, population, endpoints, status and results in the official registration, together with the extent to which the material has actually been obtained.
Conditions for verification: Do not treat the indexed description and application shell as complete registry results. Do not link the B1/B6/B12 combination to B6 monotherapy.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: 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.
Referenced methods: 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

N28 · Can a direct NRS effect of B6 alone be verified from the ADA/AAN guidelines?

Required materials and conditions: The guidelines' actual recommendations and evidence links, and results from the relevant monotherapy pain trials.
Conditions for verification: Distinguish guidelines used as clinical context from direct effect evidence; do not use absence from a recommendation list as evidence of no effect.
Requirement and applicability: Supplementary; essential for interpreting clinical context
Application exceptions: This table is not a guideline replacing existing pain treatment. Do not infer the absence of original studies solely from a guideline's list.
Why this condition is needed: Needed to avoid conflating clinical recommendations with a specific ingredient's direct effect estimate.
Referenced methods: 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

N29 · Can the favorable, no-difference and unfavorable directions of unique eligible NRS results be compared together?

Required materials and conditions: Between-group NRS estimates and intervals from unique eligible trials, and differences in populations, interventions, timepoints and analyses.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: Do not turn statistical nonsignificance into an effect of 0 or equivalence. Differences across scales or populations do not automatically constitute conflicting data.
Why this condition is needed: Needed to avoid filling gaps with only favorable adjacent results or treating dissimilar results as conflicts.
Referenced methods: 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

N30 · Can product supply, research funding, author conflicts of interest and independence be verified?

Required materials and conditions: Supply of the active agent and placebo, full funding, employment, patents, disclosed COI, and links to institutions/study families.
Conditions for verification: Distinguish verified supply arrangements from unverified full funding and COI; do not automatically grant independence or automatically exclude company-related results.
Requirement and applicability: Supplementary; essential for claims of independence
Application exceptions: Do not discard results because of company involvement. Do not state that there are no conflicts of interest because disclosures could not be read.
Why this condition is needed: The actual scope of disclosures must be explained without treating product supply as independent funding or proof of bias.
Referenced methods: 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

N31 · Can harm events, denominators and collection methods be verified for the same exposure and population?

Required materials and conditions: Definitions, collection, severity and discontinuations relating to new/worsening sensory neuropathy, plus group-specific counts of people with events, exposure denominators and duration.
Conditions for verification: 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.
Requirement and applicability: Supplementary; essential for interpreting safety
Application exceptions: 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.
Why this condition is needed: Similar neuropathy symptoms can be treatment targets and harm events, so separate verification is needed.
Referenced methods: 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

N32 · Can the minimum dose and duration associated with risk of harm, and recovery after discontinuation, be verified?

Required materials and conditions: Timing of exposure initiation, duration, event onset/worsening, discontinuation and recovery, with the relevant population and products.
Conditions for verification: Link only verified temporal relationships; do not estimate a minimum threshold, complete recovery or recovery timing.
Requirement and applicability: Supplementary; essential for claims about timing and safety thresholds
Application exceptions: 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.
Why this condition is needed: Needed to avoid turning gaps in temporal relationships into a safe dose or a guarantee of recovery.
Referenced methods: 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

N33 · Can all B6 products, concomitant medicines and other causes of symptom worsening be verified?

Required materials and conditions: Total exposure by food, supplements/medicines and vitamers, concomitant medicines, underlying disease, and alternative causes of new/worsening symptoms.
Conditions for verification: Separately verify the effects of multiple products and underlying disease; do not automatically attribute symptom worsening to diabetes or a single product.
Requirement and applicability: Supplementary; essential for extensions to causality and individual safety
Application exceptions: 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.
Why this condition is needed: Distinguishing tingling as a target of efficacy from supplementation-related harm requires verification of concurrent exposures and alternative causes.
Referenced methods: 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

N34 · Can current official nutritional upper limits, the scope of preparations and implementation status be verified?

Required materials and conditions: Sources and populations for US/EFSA nutritional upper limits, the Australian scope of preparations, effective dates and the original cutoff date.
Conditions for verification: 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.
Requirement and applicability: Supplementary; essential for nutritional and regulatory interpretation
Application exceptions: No new checks of legislation or official websites are performed in this review. Do not describe a historical planned date as current implementation.
Why this condition is needed: 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.
Referenced methods: 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

N35 · Are there direct safety data on long-term/rare harms and vulnerable groups?

Required materials and conditions: 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.
Conditions for verification: Do not extend short observations of adjacent efficacy or nutritional upper limits to long-term safety or safety in vulnerable groups.
Requirement and applicability: Supplementary; essential for long-term safety and safety in vulnerable groups
Application exceptions: Not every study of rare harms is required as an efficacy condition for the current narrow NRS question. Broader safety claims require direct data.
Why this condition is needed: Needed to avoid extending data from short-term observation or limited populations to overall safety.
Referenced methods: M19 §19.1.2–19.2.4; custom application

N36 · Are the historical access level of each material and the scope actually read on this occasion distinguished?

Required materials and conditions: The access_level and location in retained citations/evidence, actual current material types, access/acquisition, reading, dates and safe links.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: 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.
Referenced methods: 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

N37 · Within which search, date and input scope was the direct result not verified?

Required materials and conditions: The original evidence cutoff and documented scope of search, selection and access, the files actually read now, and unacquired logs/registrations.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: 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.
Referenced methods: 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

N38 · Are the original ?, empty values, B/P and the limited meaning of no_human_study preserved?

Required materials and conditions: The original grade, score, axes, strengths/calculation status, and endpoint-scoped interpretation of no_human_study.
Conditions for verification: 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.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: 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.
Referenced methods: 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

N39 · Can independent replication of directly eligible monotherapy NRS studies be verified?

Required materials and conditions: Unique trials/report families, direct NRS results, denominators, institutions, funding and differences in conditions.
Conditions for verification: Do not use the number of reports, the 7 adjacent families or reviews as the number of directly eligible studies or as independent replication.
Requirement and applicability: Required
Application exceptions: 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.
Why this condition is needed: The existence of material families and independent replication of monotherapy NRS results are different facts.
Referenced methods: 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

N40 · Does the pain NRS question require outcomes of neural recovery, disease prevention or mortality?

Required materials and conditions: Separate outcome definitions for mean pain and for nerve conduction, PLP, blood glucose, function and disease events.
Conditions for verification: 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.
Requirement and applicability: Supplementary; essential for extended claims
Application exceptions: Do not reuse this NA for a claim about another clinical effect. Keep harm conditions separate.
Why this condition is needed: Needed to avoid unnecessarily requiring other clinical endpoints for the narrow pain question or extending numerical improvement to effects on clinical events.
Referenced methods: 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

Referenced methods and the sections actually reviewed

M03 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13

Referenced principle: Clearly record the question, eligibility criteria and reasons for changes, and distinguish variations of the intervention.
Extent of review: 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

M04 · Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03

Official methodology · §4.5, §4.6.1–4.6.3, MECIR C42

Referenced principle: Distinguish and link studies and reports, and do not omit studies solely because results are unreported.
Extent of review: 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

M08 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §8.1–8.2.3, Table 8.2.a

Referenced principle: Fix the outcome and effect of interest, and examine randomization, deviations, missingness, measurement and selective reporting.
Extent of review: 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

M15 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §15.2.4, §15.3.1–15.3.3

Referenced principle: Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.
Extent of review: 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

M19 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §19.1.2, §19.2.1–19.2.4

Referenced principle: Harm questions may require designs, populations and follow-up different from those for efficacy. Case reports do not establish incidence rates.
Extent of review: 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

What the statuses mean

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

Change history

2026-11-02 · Public page/material version 1.0

The public display and materials were created from the existing 40 items. No new clinical search, change in verification status or scoring was performed.

The stored-material review date (2026-10-05) and original evidence cut-off (2026-09-15) were retained unchanged.

Researcher downloads

These materials provide the same evidence, scope and verification status as this page.

View all item details

N01 · Which population, intervention, comparator and pain outcome are being examined as a single question?

Current findings: 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.
Verification status: Verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: There is no gap in the identity of the subject being judged, but the actual eligible dose, duration, scale and denominator remain separately unverified.
Required materials and conditions: 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.
Materials to obtain first: When revising the claim, record the manuscript, facets, reasons and identity before and after the revision.
Further research: First screen studies that retain this question, and extract combinations, deficiency correction and other endpoints separately.
Remaining 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.
Conditions for verification: 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.
Why this condition is needed: Fixing this scope prevents categorical improvement or combination-product results from substituting for the NRS effect of monotherapy.
Application exceptions: 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.
Referenced methods: 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

Related sources S01 S02 S03 S04

N02 · Do the actual study ingredient, route and formulation match the question about pyridoxine hydrochloride alone?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in eligible product composition, manufacturing origin, release type, purity and batch.
Required materials and conditions: The vitamer, salt and all active ingredients; oral route; and tablet release type, purity, batch and manufacturing origin.
Materials to obtain first: Investigational-product and placebo specifications, manufacturing documents and quality documents for each candidate.
Further 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.
Remaining uncertainty: Gaps in eligible product composition, manufacturing origin, release type, purity and batch.
Conditions for verification: Distinguish oral pyridoxine hydrochloride alone from a PLP/B12/folate combination, and link only the formulation actually verified to the relevant study.
Why this condition is needed: Differences in vitamers, salts and combination composition directly affect attribution to a single ingredient.
Application exceptions: 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.
Referenced methods: 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

Related sources S01 S02 S05 S13

N03 · Were participants selected as having painful diabetic DSPN?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: Information on diabetes and a symptomatic population is available, but direct eligibility in terms of pain diagnosis, selection procedures and baseline pain is unverified.
Reason for missing information: Gaps in the diagnostic protocol, selection based on pain and detailed baseline status.
Required materials and conditions: Diagnostic and selection criteria for diabetes, distal symmetric neuropathy and pain; age, baseline pain and exclusion criteria.
Materials to obtain first: Selection and exclusion criteria and baseline-characteristics tables for Levin and McCann/Cohen.
Further research: Define diabetic distal symmetric neuropathy and pain in advance, and separate results for other neuropathies and populations treated to correct deficiency.
Remaining uncertainty: Gaps in the diagnostic protocol, selection based on pain and detailed baseline status.
Conditions for verification: Compare the actual participant diagnoses with the fixed question; do not establish eligibility for painful DSPN solely from the wording symptomatic diabetes.
Why this condition is needed: A population with symptomatic diabetes cannot automatically be treated as the same eligible population as precisely diagnosed painful DSPN.
Application exceptions: 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.
Referenced methods: 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

Related sources S01 S02 S03 S04

N04 · Are data available to distinguish correction of B6 deficiency from the separate questions concerning kidney disease, pregnancy and lactation?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: The preserved inputs contain no direct NRS results by population stratum or information on deficiency assessment and inclusion of special populations.
Reason for missing information: Gaps in direct results by strata of deficiency, kidney function, pregnancy and lactation.
Required materials and conditions: Assessment of baseline deficiency and participants by stratum; inclusion of participants by kidney function, pregnancy and lactation; and direct pain estimates.
Materials to obtain first: Baseline B6 assessment; participants, pain and harm results by stratum; and selection/exclusion tables.
Further 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.
Remaining uncertainty: Gaps in direct results by strata of deficiency, kidney function, pregnancy and lactation.
Conditions for verification: Separate treatment solely to correct deficiency from the specified pain-efficacy question, and do not infer an analgesic effect solely from low B6 indices.
Why this condition is needed: Differences in baseline nutritional status and safety in special populations limit generalization of the NRS effect of monotherapy.
Application exceptions: Do not require studies of every special population for the narrow adult NRS question. Direct data are needed for claims extending to those populations.
Referenced methods: 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

Related sources S13 S14

N05 · Are the actual comparator groups’ background care and placebo contents verified?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in background care, actual maintenance and changes, and placebo composition for a direct NRS comparison.
Required materials and conditions: Investigational-product and placebo composition; diet, medication, analgesics and rescue medication in both groups; and records of changes.
Materials to obtain first: Investigational-product/placebo documents for each candidate, and tables of concomitant medication, rescue medication and changes by group.
Further research: Define background care in both groups and record medication changes and rescue use, linking them to interpretation of assignment and adherence effects.
Remaining uncertainty: Gaps in background care, actual maintenance and changes, and placebo composition for a direct NRS comparison.
Conditions for verification: 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.
Why this condition is needed: Needed to avoid wrongly attributing differences in concomitant or rescue medication to pyridoxine’s contribution to pain outcomes.
Application exceptions: Do not require every treatment change to be identical. Verify the actual effect of interest and how changes were handled in the analysis.
Referenced methods: 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

Related sources S02 S03 S04

N06 · Are the actual dose and administration schedule for an eligible mean NRS comparison verified?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: The adjacent dose schedule is preserved, but an eligible dose used to assess NRS efficacy and actual total exposure have not been verified.
Reason for missing information: Gaps in the dose for direct NRS assessment and actual intake; 150 mg/day is a historical calculated value.
Required materials and conditions: The connection between actual dose, frequency, total B6 exposure and the corresponding NRS result; identification of totals derived from historical schedules.
Materials to obtain first: Dosing, adherence and product-specific B6 records for the candidates, and the source of the original dose calculation.
Further 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.
Remaining uncertainty: Gaps in the dose for direct NRS assessment and actual intake; 150 mg/day is a historical calculated value.
Conditions for verification: 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.
Why this condition is needed: Distinguishing an adjacent schedule from a dose with direct efficacy evidence prevents data conversion from becoming a new prescribing claim.
Application exceptions: 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.
Referenced methods: 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

Related sources S01 S02 S03 S04

N07 · Are the measurement time point, treatment duration and post-discontinuation follow-up for eligible NRS results verified?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: The adjacent duration is verified, but it cannot be directly linked to mean NRS at the same time point or to sustained effects.
Reason for missing information: Gaps in NRS assessment time points, treatment duration and follow-up after discontinuation.
Required materials and conditions: Actual NRS collection time points; treatment, follow-up and discontinuation periods; and separate results on sustained effects.
Materials to obtain first: Visit schedules, pain tables, follow-up data and discontinuation data for each candidate.
Further research: Prespecify the NRS assessment window and end time point, and examine sustained effects through separate estimates after treatment ends.
Remaining uncertainty: Gaps in NRS assessment time points, treatment duration and follow-up after discontinuation.
Conditions for verification: 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.
Why this condition is needed: Linking the endpoint to the observation period prevents old categorical observations from being read as sustained NRS effects.
Application exceptions: 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.
Referenced methods: 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

Related sources S01 S02 S03 S04

N08 · Did an actual eligible study use a validated mean pain NRS?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in the direct NRS measurement instrument and assessment procedures.
Required materials and conditions: Scale name, range, direction and validity; collection procedures and time points; and the definition of mean pain.
Materials to obtain first: Pain measurement instruments and collection descriptions in the candidates’ original reports and protocols.
Further research: Prespecify the validated NRS, collection window and direction, and report mixed pain-or-paresthesia categories separately.
Remaining uncertainty: Gaps in the direct NRS measurement instrument and assessment procedures.
Conditions for verification: 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.
Why this condition is needed: Without matching scales, responder counts and differences in mean pain cannot be compared as the same outcome.
Application exceptions: Do not enter 0–10 as the NRS range actually used. Preserve other scales with their original values and definitions, without automatic conversion.
Referenced methods: 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

Related sources S01 S02 S03 S04

N09 · Are Levin’s −1/0/+1/+2 categories eligible as direct mean NRS results?

Current findings: 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.
Verification status: Not met
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Direct mean NRS cannot be derived from these categories; whether separate NRS results were reported is unverified.
Required materials and conditions: The meaning of the original symptom categories, their pain/paresthesia composition and measurement differences from NRS.
Materials to obtain first: The complete original pain measurements and results from Levin, and whether NRS was reported separately.
Further research: Extract ordinal categories using their original definitions and check whether direct NRS results were reported separately. Do not invent means or standard deviations.
Remaining uncertainty: Direct mean NRS cannot be derived from these categories; whether separate NRS results were reported is unverified.
Conditions for verification: 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.
Why this condition is needed: Separating known ineligible scales prevents them from filling gaps in eligible pain-effect results.
Application exceptions: 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.
Referenced methods: 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

Related sources S01 S02

N10 · Do 6/9 versus 4/9 represent mean NRS or a 50% pain-response rate?

Current findings: 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.
Verification status: Not met
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: No connection to direct mean NRS or to a 50% response criterion.
Required materials and conditions: The original response definition, pain/paresthesia composition, denominator for each response and distinction from mean pain outcomes.
Materials to obtain first: The original response definition, participant-level distinctions between pain and paresthesia, and separate NRS tables.
Further research: Report mean pain and prespecified response measures separately, linking each result to its denominator.
Remaining uncertainty: No connection to direct mean NRS or to a 50% response criterion.
Conditions for verification: 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.
Why this condition is needed: Reading responder counts as a mean difference or as a different response criterion misattributes both the effect and the denominator.
Application exceptions: 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.
Referenced methods: 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

Related sources S01 S02

N11 · Can the denominators for allocation, symptom response, completion, and NRS analysis be distinguished?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: Allocation and categorical-response denominators are verified, but denominators for completion, visits, and direct NRS analysis are unverified.
Reason for missing information: Gaps in completion counts, measurement/analysis counts by endpoint, and visit flow.
Required materials and conditions: Allocation and participant flow by group, symptom-response denominators, visit completion, and counts measured and analyzed for NRS.
Materials to obtain first: Participant flow diagrams by group and tables of visits, pain measurements, and analyses.
Further research: Extract allocation, measurement, completion, and analysis denominators for each endpoint/visit, without using them interchangeably.
Remaining uncertainty: Gaps in completion counts, measurement/analysis counts by endpoint, and visit flow.
Conditions for verification: 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.
Why this condition is needed: Needed to avoid transferring a verified sample size to the analysis denominator for an unverified pain outcome.
Application exceptions: Do not state that there were no participants because a denominator is empty. Keep the McCann/Cohen denominators unverified in their separate candidate records.
Referenced methods: 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

Related sources S01 S02

N12 · Can baseline, change, and endpoint mean NRS values be directly verified?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in direct NRS baseline, change, and endpoint means and time points.
Required materials and conditions: Group-specific baseline, change, and endpoint NRS means, units, time points, and analysis populations.
Materials to obtain first: Group-specific pain results tables and analysis definitions for eligible candidates.
Further research: Extract baseline, change, and endpoint values separately and specify in advance the between-group effect to be estimated.
Remaining uncertainty: Gaps in direct NRS baseline, change, and endpoint means and time points.
Conditions for verification: 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.
Why this condition is needed: The lack of available mean values is a key gap that prevents direct evaluation of the pain effect of interest.
Application exceptions: 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.
Referenced methods: 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

Related sources S01 S02 S03 S04

N13 · Are the SD, SE, sample size, and type of error statistic for direct NRS results verified?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: Without material verifying direct NRS variance and the type of error statistic, the inputs needed to judge precision cannot be linked.
Reason for missing information: Gaps in SD/SE, variance, and the corresponding n.
Required materials and conditions: Group-specific variances for NRS changes/endpoint values, the SD/SE labels and n, and covariance and model descriptions where needed.
Materials to obtain first: Statistical notes, variance, n, and analysis models for the direct NRS results tables.
Further 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.
Remaining uncertainty: Gaps in SD/SE, variance, and the corresponding n.
Conditions for verification: Verify the actual type of error statistic, endpoint, time point, and denominator; do not reconstruct unreported variance from categorical responses.
Why this condition is needed: Direct interpretation of significance or CIs is not possible without the original type of error statistic and denominator.
Application exceptions: Do not assign a new low-precision grade solely because variance is unavailable. Do not transfer values from an ineligible scale into NRS variance.
Referenced methods: 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

Related sources S01 S02 S03 S04

N14 · Are the between-group difference, CI, P value, and effect of interest for the fixed NRS question verified?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: Without an analysis population, model, or direct NRS estimate, the direction, magnitude, and interval of the between-group effect cannot be verified.
Reason for missing information: Gaps in the between-group NRS estimate, CI, P value, model, and denominator.
Required materials and conditions: Effects of assignment/adherence, the model, direction, CI, P value, and analysis denominator for the difference in changes or endpoint values.
Materials to obtain first: The candidate's analysis plan, between-group pain results, and statistical explanation.
Further 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.
Remaining uncertainty: Gaps in the between-group NRS estimate, CI, P value, model, and denominator.
Conditions for verification: 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.
Why this condition is needed: A pain-effect estimate versus placebo cannot be constructed from mean values or counts of favorable responses alone.
Application exceptions: 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.
Referenced methods: 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

Related sources S01 S02 S03 S04

N15 · Is there an applicable threshold for an important difference with which to interpret the direct NRS effect?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in valid evidence for an important difference and a direct interval.
Required materials and conditions: An MCID or justified important difference for the same population, scale, and assessment window, together with the interval for the direct effect.
Materials to obtain first: Evidence on clinical importance for the relevant painful DSPN population and NRS, and eligible between-group estimates.
Further 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.
Remaining uncertainty: Gaps in valid evidence for an important difference and a direct interval.
Conditions for verification: Compare thresholds supported by actual sources with direct NRS intervals. Do not invent universal minimum participant counts, durations, trial counts, or an arbitrary MCID.
Why this condition is needed: Significance or participant counts alone cannot establish the clinical meaning of pain improvement.
Application exceptions: Do not fill the gap by proposing unsupported numerical thresholds. If no importance threshold is available, retain the manuscript's unverified status.
Referenced methods: M15 §15.3.1–15.3.3; custom application

Related sources S01 S02 S03 S04

N16 · Can actual allocation, concealment, and baseline balance be verified?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in allocation-sequence generation, concealment, baseline balance, and the unverified candidate designs.
Required materials and conditions: Parallel/crossover/cluster structure, random-sequence generation and allocation-concealment procedures, and baseline characteristics by group.
Materials to obtain first: Methods sections, randomization procedures, and baseline tables for each candidate.
Further 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.
Remaining uncertainty: Gaps in allocation-sequence generation, concealment, baseline balance, and the unverified candidate designs.
Conditions for verification: 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.
Why this condition is needed: Known allocation descriptions must be distinguished from unverified concealment and baseline balance to assess actual comparability.
Application exceptions: 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.
Referenced methods: M08 §8.1–8.2.3; custom application

Related sources S02 S03 S04

N17 · Are blinding and collection procedures for subjective pain assessment verified?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in direct NRS collection, assessment blinding, and whether blinding succeeded.
Required materials and conditions: Blinding of participants, care providers, and assessors; placebo appearance; NRS collection methods; and differences in measurement between groups.
Materials to obtain first: The candidate's assessment procedures, placebo description, pain-collection procedures, and blinding materials.
Further research: Specify the NRS collection window, who collects it, handling of omissions, and identical procedures across groups, and examine actual limitations in blinding.
Remaining uncertainty: Gaps in direct NRS collection, assessment blinding, and whether blinding succeeded.
Conditions for verification: Distinguish a double-blind description from actual pain-collection procedures, and do not assign successful blinding or absence of measurement bias without evidence.
Why this condition is needed: Patient-reported pain must be reviewed in relation to the actual collection and blinding conditions.
Application exceptions: Do not treat inability to blind as an automatic failure. A double-blind label does not establish eligibility of direct NRS measurement.
Referenced methods: M08 Table 8.2.a, M03 §3.2.4; custom application

Related sources S02 S03 S04

N18 · Can actual adherence, analgesics, rescue medication, and treatment changes be verified?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: The current input does not verify the numbers or methods concerning actual adherence, concomitant treatment, rescue use, or their effects on group-specific analyses.
Reason for missing information: Gaps in group-specific records of adherence, concomitant treatment, treatment deviations, and rescue medication.
Required materials and conditions: Actual intake and adherence by group, concomitant analgesics, rescue medication, treatment changes, and their handling in the analysis.
Materials to obtain first: Candidate-specific tables of dosing, concurrent treatments, rescue medication, and treatment deviations, with analysis plans.
Further research: Distinguish the effect of assignment from the effect of adherence, and report and analyze rescue medication and treatment changes in a prespecified manner.
Remaining uncertainty: Gaps in group-specific records of adherence, concomitant treatment, treatment deviations, and rescue medication.
Conditions for verification: Distinguish maintenance instructions from actual behavior, and link the handling of changes by group to their impact on the effect of interest.
Why this condition is needed: Deviations from treatment and other pain-relief interventions may explain differences in pain, so they need separate documentation.
Application exceptions: Do not require every change to be identical. The current unverified status does not establish nonadherence or unequal treatment.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; custom application / M08 §8.2.2, M15 §15.3.1; custom application

Related sources S02 S03 S04

N19 · Are NRS missingness, dropouts, and the actual analysis populations and handling verified?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in NRS missingness, dropouts, analysis populations, and sensitivity data.
Required materials and conditions: Reasons for missing NRS data and dropouts at each visit, ITT/PP, analysis n, handling of missing data, and sensitivity analyses.
Materials to obtain first: Visit-specific NRS data flow, dropout tables, and analysis plans/descriptions of missing-data handling.
Further research: Extract endpoint-specific missingness and reasons by group, and prespecify analysis and sensitivity methods appropriate to the effect of interest.
Remaining uncertainty: Gaps in NRS missingness, dropouts, analysis populations, and sensitivity data.
Conditions for verification: Verify the original analysis population and endpoint-specific missingness, without inferring NRS ITT populations or completion counts from allocation counts or categorical denominators.
Why this condition is needed: Missing data and actual analysis counts are directly needed to interpret mean pain estimates.
Application exceptions: Do not convert unverified missingness into confirmed attrition bias or 0 dropouts. Also retain the existence of ineligible categorical results.
Referenced methods: 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

Related sources S01 S02 S03 S04

N20 · Can prespecified pain endpoints, analyses, and time points be compared with actual reporting?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: Materials comparing plans with results for direct monotherapy NRS candidates have not been obtained, so whether selective reporting occurred cannot be verified.
Reason for missing information: Gaps in comparisons of prospective plans, endpoint hierarchies, and changes for monotherapy candidates.
Required materials and conditions: Registrations, protocols, and analysis plans for monotherapy candidates; pain-endpoint hierarchy, time points, multiplicity, and reasons for changes.
Materials to obtain first: Registration, protocol, analysis plan, and correction/result reports for each monotherapy candidate.
Further research: Compare prespecified pain endpoints, analyses, and time points with actual results, and separately record reasons for changes and multiple comparisons.
Remaining uncertainty: Gaps in comparisons of prospective plans, endpoint hierarchies, and changes for monotherapy candidates.
Conditions for verification: Compare only plans and results that have actually been obtained. Do not describe an unavailable plan as proof of nonregistration or selective reporting.
Why this condition is needed: Comparison with actual plans is needed to avoid treating the current results gap as proof of selective reporting.
Application exceptions: 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.
Referenced methods: 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

Related sources S02 S03 S04 S05 S08

N21 · Can the monotherapy, comparator, pain scale, and results of McCann 1983 be directly verified?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in McCann's original methods, results, and eligibility.
Required materials and conditions: The original article's methods, formulation/dose, comparator, population, pain instrument, and results/denominators, and their agreement with the review's citation.
Materials to obtain first: McCann's original article, supplementary results, any corrections, and the corresponding primary reference in the review.
Further 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.
Remaining uncertainty: Gaps in McCann's original methods, results, and eligibility.
Conditions for verification: 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.
Why this condition is needed: Unverified monotherapy candidates must be retained to describe honestly the scope of the current direct-evidence gap.
Application exceptions: 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.
Referenced methods: 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

Related sources S03 S15

N22 · Can the pain instrument, comparator, and direct results of Cohen 1984 be verified?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in Cohen's original results, methods, scale, and denominators; historical access failure.
Required materials and conditions: The original article's population, single-ingredient composition, design, pain instrument/time point, denominators, and results, together with the actual access history.
Materials to obtain first: Cohen's original article, supplementary results, methods, corrections, and lawful access routes.
Further 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.
Remaining uncertainty: Gaps in Cohen's original results, methods, scale, and denominators; historical access failure.
Conditions for verification: Do not use PubMed metadata or the publisher403 record from that time as original results. Verify direct NRS eligibility after obtaining the results.
Why this condition is needed: Retain its status as a separate candidate to avoid confusing failed access with negative pain findings.
Application exceptions: 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.
Referenced methods: 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

Related sources S04

N23 · Are all links between reports and actual study families verified?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: The current identity/source material for S17 in the McCann family is missing; the number of unique eligible trials remains undetermined.
Required materials and conditions: Correspondence between report IDs, DOI/PMID, families, and the original material list, and the identity of missing references.
Materials to obtain first: Original identity documentation for the S17 reference and a table linking included trials and reports for each candidate.
Further research: Link report→study family→endpoint/timepoint/analysis, and manage missing IDs as provisional references until verified.
Remaining uncertainty: The current identity/source material for S17 in the McCann family is missing; the number of unique eligible trials remains undetermined.
Conditions for verification: 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.
Why this condition is needed: Needed to distinguish report counts from study counts and avoid mistaking a missing reference for replicated numerical evidence.
Application exceptions: 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.
Referenced methods: 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

Related sources S01 S02 S03 S15

N24 · Does Metanx provide a direct comparison of mean NRS for pyridoxine hydrochloride alone?

Current findings: 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.
Verification status: Not met
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: No link between the monotherapy contribution and direct mean NRS results.
Required materials and conditions: Full PLP/folate/B12 composition, primary VPT/secondary NTSS-6, and results isolating the B6 contribution.
Materials to obtain first: Original Metanx methods, composition, primary/secondary results, and direct data isolating component contributions.
Further research: Retain combination results by study family and separately check for monotherapy comparisons or comparisons isolating component contributions.
Remaining uncertainty: No link between the monotherapy contribution and direct mean NRS results.
Conditions for verification: 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.
Why this condition is needed: Needed to prevent misattribution to monotherapy while retaining favorable combination results.
Application exceptions: Do not label results for the combination as showing no effect. Do not convert VPT/NTSS-6 to NRS.
Referenced methods: 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

Related sources S05

N25 · Do Dawood's metabolic and oxidative-stress results directly answer the painful DSPN NRS question?

Current findings: 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.
Verification status: Not met
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: No direct link to the specified population and mean NRS.
Required materials and conditions: The newly diagnosed T2DM/metformin population, actual pain diagnosis and endpoints, and a comparison of B6 alone.
Materials to obtain first: Complete original definitions of Dawood's participant selection, intervention, metabolic outcomes and pain outcomes.
Further research: Extract biomarkers as separate outcomes and verify whether painful DSPN and direct NRS results were actually reported.
Remaining uncertainty: No direct link to the specified population and mean NRS.
Conditions for verification: Do not substitute oxidative-stress or metabolic results for the same pain outcome; verify alignment of the actual population, intervention and NRS.
Why this condition is needed: Shared references to diabetes and vitamins alone do not justify treating metabolic markers as patient-reported pain outcomes.
Application exceptions: Do not erase the significance of the verified metabolic study. Do not conclude that other results are absent from an unread original.
Referenced methods: 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

Related sources S06

N26 · Is Bae's foot-pain improvement an eligible diabetes-specific NRS result versus placebo?

Current findings: 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.
Verification status: Not met
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: No direct link to a separately identified diabetic population and a placebo-controlled NRS estimate.
Required materials and conditions: A separately identified diabetic DSPN population, pain instrument, comparison group, denominator, timepoint and between-group estimate.
Materials to obtain first: Bae's original population, pain scale, timepoints, participant flow and any available comparison data.
Further research: Retain mixed-population results within their original scope and check whether separate controlled results exist for the specified population.
Remaining uncertainty: No direct link to a separately identified diabetic population and a placebo-controlled NRS estimate.
Conditions for verification: Do not treat uncontrolled improvement in a mixed population as a control-adjusted effect; verify that the specified population and actual comparison align.
Why this condition is needed: Before-and-after improvement and an effect versus placebo are different estimates, so the actual study design must be verified.
Application exceptions: 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.
Referenced methods: 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

Related sources S07

N27 · Can the use of monotherapy, latest status and pain results for NCT04689971 be verified?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in the registry text, latest status and actual results/denominators; mismatch with monotherapy.
Required materials and conditions: Intervention composition, population, endpoints, status and results in the official registration, together with the extent to which the material has actually been obtained.
Materials to obtain first: Complete intervention, endpoint, result and amendment history from the official registration.
Further research: Link registration, results and publication reports within study families, distinguishing planned information from actual results.
Remaining uncertainty: Gaps in the registry text, latest status and actual results/denominators; mismatch with monotherapy.
Conditions for verification: Do not treat the indexed description and application shell as complete registry results. Do not link the B1/B6/B12 combination to B6 monotherapy.
Why this condition is needed: 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 exceptions: 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.
Referenced methods: 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

Related sources S08

N28 · Can a direct NRS effect of B6 alone be verified from the ADA/AAN guidelines?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gap between guideline context and a direct NRS estimate for monotherapy.
Required materials and conditions: The guidelines' actual recommendations and evidence links, and results from the relevant monotherapy pain trials.
Materials to obtain first: The relevant guideline evidence tables and recommendations, linked to the actual original trials.
Further 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.
Remaining uncertainty: Gap between guideline context and a direct NRS estimate for monotherapy.
Conditions for verification: Distinguish guidelines used as clinical context from direct effect evidence; do not use absence from a recommendation list as evidence of no effect.
Why this condition is needed: Needed to avoid conflating clinical recommendations with a specific ingredient's direct effect estimate.
Application exceptions: This table is not a guideline replacing existing pain treatment. Do not infer the absence of original studies solely from a guideline's list.
Referenced methods: 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

Related sources S09 S10

N29 · Can the favorable, no-difference and unfavorable directions of unique eligible NRS results be compared together?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in the directions, conditions and intervals of unique eligible NRS results.
Required materials and conditions: Between-group NRS estimates and intervals from unique eligible trials, and differences in populations, interventions, timepoints and analyses.
Materials to obtain first: Complete results for each candidate, including no-difference and unfavorable results, and corrections.
Further 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.
Remaining uncertainty: Gaps in the directions, conditions and intervals of unique eligible NRS results.
Conditions for verification: 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.
Why this condition is needed: Needed to avoid filling gaps with only favorable adjacent results or treating dissimilar results as conflicts.
Application exceptions: Do not turn statistical nonsignificance into an effect of 0 or equivalence. Differences across scales or populations do not automatically constitute conflicting data.
Referenced methods: 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

Related sources S01 S02 S03 S04 S05 S07

N30 · Can product supply, research funding, author conflicts of interest and independence be verified?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in full funding, author COI and institutional relationships.
Required materials and conditions: Supply of the active agent and placebo, full funding, employment, patents, disclosed COI, and links to institutions/study families.
Materials to obtain first: Funding/COI wording, product supply, institutions and related reporting information for each candidate.
Further research: Extract funding, product supply and author relationships from the original text, and review the independence claim and relevance to the results separately.
Remaining uncertainty: Gaps in full funding, author COI and institutional relationships.
Conditions for verification: Distinguish verified supply arrangements from unverified full funding and COI; do not automatically grant independence or automatically exclude company-related results.
Why this condition is needed: The actual scope of disclosures must be explained without treating product supply as independent funding or proof of bias.
Application exceptions: Do not discard results because of company involvement. Do not state that there are no conflicts of interest because disclosures could not be read.
Referenced methods: 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

Related sources S02 S05

N31 · Can harm events, denominators and collection methods be verified for the same exposure and population?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in event definitions, counts of people, denominators and systematic collection for the same population and exposure.
Required materials and conditions: Definitions, collection, severity and discontinuations relating to new/worsening sensory neuropathy, plus group-specific counts of people with events, exposure denominators and duration.
Materials to obtain first: Harm and discontinuation result tables for the candidates, and the actual harm data cited by official warnings.
Further 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.
Remaining uncertainty: Gaps in event definitions, counts of people, denominators and systematic collection for the same population and exposure.
Conditions for verification: 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.
Why this condition is needed: Similar neuropathy symptoms can be treatment targets and harm events, so separate verification is needed.
Application exceptions: 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.
Referenced methods: 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

Related sources S11 S12 S13

N32 · Can the minimum dose and duration associated with risk of harm, and recovery after discontinuation, be verified?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in event timing, minimum thresholds and recovery estimates for the same exposure.
Required materials and conditions: Timing of exposure initiation, duration, event onset/worsening, discontinuation and recovery, with the relevant population and products.
Materials to obtain first: Timelines of exposure, discontinuation and events/recovery, and harm reports with adequate follow-up.
Further research: Extract temporal sequence and the course after discontinuation from individual records; do not extrapolate recovery or thresholds beyond the observation period.
Remaining uncertainty: Gaps in event timing, minimum thresholds and recovery estimates for the same exposure.
Conditions for verification: Link only verified temporal relationships; do not estimate a minimum threshold, complete recovery or recovery timing.
Why this condition is needed: Needed to avoid turning gaps in temporal relationships into a safe dose or a guarantee of recovery.
Application exceptions: 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.
Referenced methods: 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

Related sources S11 S12

N33 · Can all B6 products, concomitant medicines and other causes of symptom worsening be verified?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in actual total exposure, concurrent treatment and alternative causes for each participant.
Required materials and conditions: Total exposure by food, supplements/medicines and vitamers, concomitant medicines, underlying disease, and alternative causes of new/worsening symptoms.
Materials to obtain first: A complete product list and ingredient/schedule details, concomitant medicines, neuropathy diagnoses and symptom timing records.
Further 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.
Remaining uncertainty: Gaps in actual total exposure, concurrent treatment and alternative causes for each participant.
Conditions for verification: Separately verify the effects of multiple products and underlying disease; do not automatically attribute symptom worsening to diabetes or a single product.
Why this condition is needed: Distinguishing tingling as a target of efficacy from supplementation-related harm requires verification of concurrent exposures and alternative causes.
Application exceptions: 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.
Referenced methods: 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

Related sources S11 S12 S13

N34 · Can current official nutritional upper limits, the scope of preparations and implementation status be verified?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Current official regulatory/nutritional documents were not rechecked in this review; no link to a direct pain-treatment dose.
Required materials and conditions: Sources and populations for US/EFSA nutritional upper limits, the Australian scope of preparations, effective dates and the original cutoff date.
Materials to obtain first: The latest editions and implementation history of the relevant official documents, and the populations and scope of the original standards.
Further research: When updating official information, verify legislation, nutritional standards and treatment effects separately while retaining the original cutoff-date record.
Remaining uncertainty: Current official regulatory/nutritional documents were not rechecked in this review; no link to a direct pain-treatment dose.
Conditions for verification: 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.
Why this condition is needed: 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 exceptions: No new checks of legislation or official websites are performed in this review. Do not describe a historical planned date as current implementation.
Referenced methods: 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

Related sources S12 S13 S14

N35 · Are there direct safety data on long-term/rare harms and vulnerable groups?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in direct data on long-term and rare harms and special populations.
Required materials and conditions: 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.
Materials to obtain first: Harm data with sufficient follow-up, and exposure, events, denominators/duration for each vulnerable group.
Further 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.
Remaining uncertainty: Gaps in direct data on long-term and rare harms and special populations.
Conditions for verification: Do not extend short observations of adjacent efficacy or nutritional upper limits to long-term safety or safety in vulnerable groups.
Why this condition is needed: Needed to avoid extending data from short-term observation or limited populations to overall safety.
Application exceptions: Not every study of rare harms is required as an efficacy condition for the current narrow NRS question. Broader safety claims require direct data.
Referenced methods: M19 §19.1.2–19.2.4; custom application

Related sources S13 S14

N36 · Are the historical access level of each material and the scope actually read on this occasion distinguished?

Current findings: 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.
Verification status: Verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: All current external clinical source materials remain unread; report-specific historical access dates are unverified.
Required materials and conditions: The access_level and location in retained citations/evidence, actual current material types, access/acquisition, reading, dates and safe links.
Materials to obtain first: Actual logs of access, acquisition and reading for each material, original locations, and complete source materials where available.
Further 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.
Remaining uncertainty: All current external clinical source materials remain unread; report-specific historical access dates are unverified.
Conditions for verification: 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.
Why this condition is needed: 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 exceptions: 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.
Referenced methods: 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

Related sources S01 S02 S03 S04 S05 S06 S07 S08 S09 S10 S11 S12 S13 S14 S15

N37 · Within which search, date and input scope was the direct result not verified?

Current findings: 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.
Verification status: Partly verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: No current new search, reading of separate logs, or verification of the completeness of registrations/corrections was performed.
Required materials and conditions: The original evidence cutoff and documented scope of search, selection and access, the files actually read now, and unacquired logs/registrations.
Materials to obtain first: The original search, selection and access logs, and future updated registration, correction and result records.
Further 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.
Remaining uncertainty: No current new search, reading of separate logs, or verification of the completeness of registrations/corrections was performed.
Conditions for verification: 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.
Why this condition is needed: 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 exceptions: 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.
Referenced methods: 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

Related sources S03 S04 S08 S15

N38 · Are the original ?, empty values, B/P and the limited meaning of no_human_study preserved?

Current findings: 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.
Verification status: Verified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: The original values and the explicit explanation of scope were preserved together. No new grading, scoring or judgment of effect was performed.
Reason for missing information: Original unscored/empty values and the direct NRS gap retained; no new judgment.
Required materials and conditions: The original grade, score, axes, strengths/calculation status, and endpoint-scoped interpretation of no_human_study.
Materials to obtain first: A separate record of approved evidence, calculations, version and reasons for change if the original judgment is changed.
Further 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.
Remaining uncertainty: Original unscored/empty values and the direct NRS gap retained; no new judgment.
Conditions for verification: 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.
Why this condition is needed: 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 exceptions: 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.
Referenced methods: 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

Related sources

N39 · Can independent replication of directly eligible monotherapy NRS studies be verified?

Current findings: 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.
Verification status: Unverified
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Gaps in unique eligible trials, independence and the distribution of direct results.
Required materials and conditions: Unique trials/report families, direct NRS results, denominators, institutions, funding and differences in conditions.
Materials to obtain first: Eligible NRS results by family and a table of institutions, funding and report relationships.
Further 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.
Remaining uncertainty: Gaps in unique eligible trials, independence and the distribution of direct results.
Conditions for verification: Do not use the number of reports, the 7 adjacent families or reviews as the number of directly eligible studies or as independent replication.
Why this condition is needed: The existence of material families and independent replication of monotherapy NRS results are different facts.
Application exceptions: 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.
Referenced methods: 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

Related sources S01 S02 S03 S04 S15

N40 · Does the pain NRS question require outcomes of neural recovery, disease prevention or mortality?

Current findings: 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.
Verification status: Not applicable
Materials actually read: The retained manuscript summaries and native values were actually read; original papers, official websites and registry records were not read in this review
Why unverified: 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.
Reason for missing information: Effects extending beyond the current question remain a separate unverified scope.
Required materials and conditions: Separate outcome definitions for mean pain and for nerve conduction, PLP, blood glucose, function and disease events.
Materials to obtain first: Direct reports on the relevant event or functional outcome if an extended claim is made.
Further research: Design pain scores and neural function/disease events as different questions, and verify each endpoint, duration and denominator independently.
Remaining uncertainty: Effects extending beyond the current question remain a separate unverified scope.
Conditions for verification: 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.
Why this condition is needed: Needed to avoid unnecessarily requiring other clinical endpoints for the narrow pain question or extending numerical improvement to effects on clinical events.
Application exceptions: Do not reuse this NA for a claim about another clinical effect. Keep harm conditions separate.
Referenced methods: 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

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