Oral dispersible methylcobalamin (vitamin B12) × Reduction in reported painDETECT score in metformin-treated diabetic neuropathy with low B12

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	Met	Full text not readStored summary read	N01 · Separate questionWhich population and which 12-month score are being compared?Required	The single question is whether adding oral methylcobalamin 1000 µg/day for 12 months lowers the reported painDETECT score compared with placebo on the same background management in adults with type 2 diabetes and confirmed peripheral and autonomic neuropathy who have used metformin for at least 4 years and have B12 <400 pmol/L. The actual subclaims list is empty. S01 S04	The identity and exclusions of the original question were verified. This does not mean that efficacy or a general analgesic effect has been established.	The original question and specifications of the population, ingredient, route, dose, comparator, time point and endpoint	Fix the original question and eligibility criteria, then separately examine only comparisons involving the same population, formulation and score.
2	Met	Full text not readStored summary read	N02 · Active ingredientWas methylcobalamin the trial's single active ingredient?Required	The manuscript records methylcobalamin (mecobalamin) as the single added active ingredient. Other cobalamins were not combined with it, and B12 fix is identified as a single-ingredient oral product. S01	The retained identity of the chemical form and single added ingredient was verified. Product purity and the trial batch were not verified.	The original trial's active ingredient, chemical form and whether it was a combination product	Compare the active-ingredient specifications with each original trial's composition to distinguish comparisons of a single added ingredient in the same chemical form.
3	Partly verified	Full text not readStored summary read	N03 · Trial productDo the supply identity and historical batch of B12 fix match?Required	B12 fix and UNI-PHARMA are identified in the retained manuscript. Manufacturing source, historical trial batch and purity are unverified; the current manufacturer page is not used as evidence that the trial batch was identical. S01 S10	Only the product name and supplier were linked. Comparison of the batch, purity and identity with the current product remains outstanding.	Trial-product supply records, batch/purity documentation and the current product description	Obtain the trial supply records and contemporaneous batch documentation, and compare them with the current product description while distinguishing their dates.
4	Met	Full text not readStored summary read	N04 · Route of administrationHas the oral dispersible formulation been reinterpreted as sublingual or injectable?Required	The actual formulation is an oral dispersible tablet. No sublingual holding time is inferred and no injection route is substituted. S01	The retained identity of the oral formulation and route was linked. Detailed dosing procedures or absorption mechanisms were not verified.	Trial administration method and oral dispersible formulation specifications	Compare the contemporaneous administration instructions to distinguish the dosing procedure from the actual route.
5	Partly verified	Full text not readStored summary read	N05 · Nominal doseHas the trial dose been distinguished from total exposure?Required	The trial administered methylcobalamin alone at 1000 µg 1 time daily for 12 months. Total exposure including diet, fortified foods and other additional supplements, and numerical adherence, are unverified. S01	The nominal trial dose and frequency were linked, but actual total exposure and adherence were not verified.	Trial dose and frequency, dietary/additional supplementation exposure and adherence records	Compare administration, additional supplementation and dietary records by group to assess differences between nominal dose and actual exposure.
6	Conflicting information	Full text not readStored summary read	N06 · Conflicting product unitsHas the manufacturer's 1000 µg versus 1000 mg labeling been resolved?Required	The retained manuscript records that the current manufacturer page displays both 1000 µg and 1000 mg. This conflict remains unresolved; the trial dose remains 1000 µg/day as specified in S01. S01 S10	The manuscript explicitly records inconsistent units on the same product page. Which label, if any, was corrected was not checked in this exercise.	Locations of the manufacturer's labels, corrections and contemporaneous trial-dose documentation	Compare labeling and correction history on the same product page with their original locations to verify the conflict, while maintaining the trial specifications separately.
7	Met	Full text not readStored summary read	N07 · Observation periodHas 12-month administration been separated from results over other durations?Required	The selected question and actual trial duration are 12 months. The 4-month nerve-conduction result in S05 is separated as a different duration and endpoint. Observation over 12 months is not reinterpreted as persistence after discontinuation. S01 S05	The selected time point and duration were linked, with the timing of adjacent results distinguished. The preregistered primary time point remains separately unverified.	Trial administration and assessment times, and the duration of each adjacent study	Compare the original time-specific tables and trial schedule to separate administration duration, observation duration and the time point of the selected outcome.
8	Partly verified	Full text not readStored summary read	N08 · Population selectionWhich adults with diabetic neuropathy were selected?Required	The population comprises adults with type 2 diabetes and confirmed peripheral and autonomic neuropathy who have used metformin for at least 4 years and have B12 <400 pmol/L. This scope is not extended to all diabetic neuropathy. S01	The core population-selection criteria were preserved, but the pain threshold for entry and minimum duration were not verified.	Population diagnoses, duration of metformin use and B12 eligibility criterion	Compare inclusion/exclusion documentation and baseline characteristics to assess the applicability boundaries of the narrowly selected population.
9	Partly verified	Full text not readStored summary read	N09 · Low-B12 boundaryIs B12 <400 pmol/L being interpreted as absolute deficiency in everyone?Required	The manuscript retains B12 <400 pmol/L as the eligibility criterion. This is not reclassified as confirmed absolute deficiency in everyone or used as evidence for supplementation in all patients with normal B12. S01	The low-B12 selection boundary was linked, but diagnoses of absolute deficiency and effects in a normal-B12 population were not verified.	Baseline B12 criterion, diagnosis of deficiency and population-specific results	Compare diagnostic evidence of deficiency with the eligibility value, and assess extension to a normal-B12 population through a separate comparison.
10	Unverified	Full text not readStored summary read	N10 · Pain entry criteriaWere the pain NRS entry threshold and minimum duration verified?Required	The authors' description of painful neuropathy is preserved, but the entry NRS criterion and minimum pain duration are unverified. S01	The exact pain entry criteria cannot be established within the retained material read. This does not mean that participants did not experience pain.	Pain diagnosis, entry NRS criterion and minimum duration in the eligibility documentation	Compare the eligibility documentation and diagnostic procedures to verify actual pain-intensity and duration entry criteria.
11	Partly verified	Full text not readStored summary read	N11 · Glycemic-status selectionWas selection for stable HbA1c of 6.5–7.5% preserved?Required	The original population is described as adults with stable HbA1c of 6.5–7.5%. Background glycemic management was maintained; the same score effect is not generalized to patients with other glycemic states. S01	The retained stability criterion and range were linked, but details of actual glycemic-medication changes and management by group are lacking.	Baseline glycemic status, stability criteria and glycemic-medication records by group	Compare baseline glycemic selection criteria and management/medication records by group to assess applicability and concomitant-treatment boundaries.
12	Partly verified	Full text not readStored summary read	N12 · Placebo specificationsWas the full composition of the similar-looking placebo verified?Required	The comparator conditions are a similar-looking placebo and stable common glycemic management. Full placebo excipients and the historical batch are unverified. S01	The framework of the placebo comparison was linked, but full composition and batch identity were not verified.	Placebo appearance, composition and batch, and common management in each group	Compare contemporaneous placebo specifications and manufacturing records to assess comparator composition and implementation of blinding.
13	Partly verified	Full text not readStored summary read	N13 · Common treatmentWere common glycemic management and adjustment variables distinguished?Required	Background glycemic management was maintained, and the formal comparison of change adjusted for HbA1c and glycemic medications. A common management policy and actual changes by group are different information; detailed change records are unverified. S01	The policy and adjustment variables were linked, but detailed comparison of actual concomitant exposure by group and the handling of changes remains outstanding.	Glycemic medications and management changes by group, and ANCOVA adjustment specifications	Compare concomitant-treatment changes by group and analysis specifications to assess the selected intervention's contribution and the effect of interest.
14	Partly verified	Full text not readStored summary read	N14 · Rescue analgesicsIs the policy permitting paracetamol the same as actual use?Required	The retained policy restricted other analgesics and permitted occasional paracetamol for only 2–3 days. The actual amount of rescue medication used is unverified. S01	The analgesic policy was verified, but actual amounts used by group and handling in the analysis were not verified.	Rescue-analgesic policy, amount used and changes by group, and handling in the analysis	Compare rescue-medication use records by group to assess the relationship between the score comparison and concurrent treatment.
15	Unverified	Full text not readStored summary read	N15 · Adherence and dietWere numerical adherence and additional B12 exposure verified?Required	Diet, fortified foods, total additional-supplement exposure and numerical adherence are unverified. The report that everyone completed 12 months does not guarantee actual intake or full adherence. S01	The material read contains no numerical data on actual exposure or adherence. Unverified information is not treated as proof of nonadherence or absence of additional supplementation.	Dosing records and numerical adherence by group, and records of diet, fortified foods and additional supplementation	Compare dosing, diet and additional-exposure records, and assess their handling in relation to the effect of interest.
16	Met	Full text not readStored summary read	N16 · Scale definitionIs the painDETECT total score a mean pain-intensity NRS?Required	The original paper-form total score in S04 has a range of −1–38. It sums sensory qualities, pain course and radiation; the items recording pain intensity are not included in the total score. The selected painDETECT score is not a mean pain NRS/VAS. S01 S04	The retained scale components and endpoint boundaries were verified. The exact language/version used in the trial and an applicable criterion for clinically important change remain separately unverified.	Original scale definition, total-score components, range and direction	Compare the original scale definition with the items actually used in the trial to assess how the total score relates to the intensity items.
17	Unverified	Full text not readStored summary read	N17 · Questionnaire implementationWere the trial questionnaire's language, version and recall period verified?Required	The exact questionnaire language, version and recall period are unverified. A historical record of reading the original painDETECT definition does not substitute for the trial's actual questionnaire implementation. S01 S04	The trial's measurement implementation cannot be established from the stored materials read. This is not a judgment that the scale is invalid.	Trial questionnaire, language/translation, version, recall period and scoring procedure	Compare the contemporaneous questionnaire and scoring procedure with the original scale definition to assess how the actual measurement corresponds to it.
18	Partly verified	Full text not readStored summary read	N18 · Selected time pointWas the page's primary endpoint at 12 months distinguished from a registered primary (1st) endpoint?Required	The selected outcome is the between-group comparison of change in reported painDETECT score at 12 months. It is the page's primary endpoint, but whether it was prespecified as primary (1st) in the original registration is unverified. S01 S03	The reported time point and the page's selection were verified, but the preregistered hierarchy could not be compared.	Outcome time points, original registration hierarchy, initial posting and amendment history	Compare the initial registration and timing of outcome reporting to assess how selection occurred and why changes were made.
19	Partly verified	Full text not readStored summary read	N19 · Allocation and blindingWas the RCT designation distinguished from implementation of allocation concealment?Required	The original trial is retained as randomized, placebo-controlled and double-blind. How allocation concealment was implemented was not reported and was included in the original B2 rationale separately from the small trial size. S01	The design designation and limitations in the original assessment were linked. Detailed implementation was not compared, and no new bias-assessment tool was applied.	Original trial design, allocation/concealment, implementation of blinding and baseline data	Compare allocation procedures, placebo specifications and assessment-blinding documentation to assess potential bias in the selected score.
20	Partly verified	Full text not readStored summary read	N20 · Allocation and completionAre allocation of 90 participants, 44/46 by group, and completion being read as analysis denominators?Required	Of 90 participants, 44 were allocated to methylcobalamin and 46 to placebo; all reportedly completed 12 months. Separate endpoint-specific analysis denominators were not reported. S01	The retained allocation and completion values were linked, but the actual painDETECT analysis denominators were not verified.	Flow diagram and denominators for allocation, completion, measurement and analysis by group	Compare the flow diagram and endpoint-specific analysis tables to link participant counts for allocation → completion → measurement → analysis.
21	Unverified	Full text not readStored summary read	N21 · Analysis population and missing dataWere the painDETECT analysis population and missing-data handling verified?Required	Endpoint-specific analysis denominators were not reported. Reported completion of 44/46 does not establish ITT, PP or 0 missing data; the original assessment also did not provide a standardized effect for endpoint values because the denominators were unverified. S01	The analysis population and missing-data handling for the selected score cannot be established from the material read. These are distinguished from the report that everyone completed the trial.	PainDETECT analysis denominators by group, analysis population, reasons for missing data/exclusions and their handling	Compare outcome-specific analysis specifications and missing-data/exclusion records to assess the effect of interest and the actual analysis population.
22	Met	Full text not readStored summary read	N22 · Original scores and descriptive differencesAre the original scores, existing change contrast and endpoint difference being read as the same estimate?Required	Table 4 reports scores of 18.4→17.1 in the methylcobalamin group and 19.3→20.9 in the placebo group. The manuscript's simple change contrast of −2.9 points and endpoint difference of −3.8 points are existing unadjusted descriptive values; neither is an unreported adjusted estimate. No new calculation was performed in this exercise. S01	The definitions, directions and attribution of the original scores and existing descriptive differences were preserved. The formal adjusted effect estimate and CI were not verified.	Scores and time points in the original results table, definitions of existing descriptive differences and adjusted results	Compare the original table and analysis definitions to assess the correspondence among original scores, descriptive differences and the formal adjusted effect.
23	Partly verified	Full text not readStored summary read	N23 · Adjusted effect and intervalHas P<0.001 been turned into an adjusted coefficient, SE or CI?Required	The formal comparison of change adjusted for HbA1c and glycemic medications reports P<0.001. The original assessment records adjusted ANCOVA, but the adjusted coefficient, SE and CI were not reported. formal_adjusted_CI is null, not 0. It is not replaced by an unadjusted descriptive difference. S01	The formal analysis type, adjustment variables and P reported as an inequality were linked. The formal effect magnitude and interval were not verified.	ANCOVA specifications, adjusted coefficient, SE, CI, denominators and results table	Compare formal model output and the results table to verify the formal effect of interest, interval and denominators.
24	Conflicting information	Full text not readStored summary read	N24 · Conflicting baseline SDHave the baseline SD values of 9.2 and 9.7 been silently harmonized?Required	The manuscript preserves the baseline SD conflict of 9.2 versus 9.7 in the original table, without harmonizing the values as though resolved. The exact table cell, group attribution or correction status of each value is not newly established from the current stored summary alone. S01	The manuscript explicitly records inconsistent values for the same baseline SD. The conflict remains unresolved because the original PDF/table was not reopened in this exercise.	Locations of baseline SD in the original Table 4 and text, corrections, and group/time-point specifications	Compare the original table, relevant text and correction history for the same group/time point to verify the location and attribution of the SD conflict.
25	Unverified	Full text not readStored summary read	N25 · Clinical importanceIs there an applicable MCID for painDETECT change in this population?Required (for interpreting clinical importance)	An applicable criterion for clinical importance is unverified. The manuscript did not assign EX solely because an MCID was absent; it separately records the unverified adjusted estimate, SE, CI and analysis denominators. S01 S04	The clinical importance of the score change in the selected population cannot be established within the current scope.	Evidence for an MCID applicable to this population, scale version and change estimate	Compare evidence on important change in the same population and scale version with the score definition, and interpret it alongside the reported interval.
26	Partly verified	Full text not readStored summary read	N26 · Registration historyWas the identity of NCT04706377 distinguished from reading its content?Required	NCT04706377 is the registration number linked to the original trial. Historical access was registration_shell_only; the record states that the initial posting date, amendment history, primary pain-endpoint hierarchy and prespecified analysis plan could not be verified. The registration was not queried in this exercise either. S01 S03	The registration identity is preserved, but comparison of the registration content and prespecified hierarchy remains incomplete.	Original registration record, initial posting, amendment history and outcome hierarchy	Compare the initial registration and amendment history with outcome reporting to assess temporal order, the selected endpoint and reasons for changes.
27	Unverified	Full text not readStored summary read	N27 · Plans and multiple endpointsWere the protocol and SAP compared with the selection of actual results?Required	The protocol, SAP and registered endpoint hierarchy are unverified. The original assessment describes multiple endpoints, prespecified hierarchy and inconsistent diagnostic criteria as separate risks; primary_failed_secondary_positive and coprimary_split in axes are null. S01 S03	Without a direct comparison of plans and reporting, prespecification, the circumstances of changes and handling of multiple endpoints are not established.	Protocol, SAP, prespecified endpoints/analyses/time points, handling of multiple endpoints and reporting	Compare the registration, protocol and SAP with all reported endpoints, analyses and time points to assess changes to the plan and reasons for selection.
28	Met	Full text not readStored summary read	N28 · Results without a significant differenceWere nonsignificant results for MNSIE and HbA1c preserved?Required	The manuscript also preserves the between-group MNSIE P=0.607 and HbA1c P=0.876. Nonsignificance for these two different endpoints is not reinterpreted as direct refutation of painDETECT, equivalence or an effect of 0. S01	The manuscript's other endpoints, results without a significant difference and attribution boundaries were preserved. Their full analyses and intervals were not verified.	All reported endpoints, denominators, time points and analyses, including favorable results and results without a significant difference	Compare each endpoint, denominator and analysis in the complete results table to assess how favorable results and those without a significant difference relate to the selected score.
29	Met	Full text not readStored summary read	N29 · Same-trial familyAre S01, S02 and S03 being counted as three replications?Required	S01's DOI 10.3390/nu13020395, PMID 33513879 and PMCID PMC7912007 correspond to the S02 bibliographic record, and NCT04706377 is linked to S03. The original trial, index and registration records in F01 are not counted as 3 independent replications. S01 S02 S03	The retained identifiers and registration linkage for the same original trial were verified. The full registration and all related reports were not exhaustively checked in this exercise.	DOI, PMID, PMCID, registration number and report-family linkage	Compare identifiers, trial numbers and original-report identities to link reports belonging to the same trial family.
30	Partly verified	Full text not readStored summary read	N30 · Adjacent 1992 trialAre improvement and the absence of a significant nerve-conduction difference in S05 being read as replication of the same question?Supplementary; required for a claim of exact replication	The 1992 abstract for F02 reported improvement in somatic and autonomic symptoms, but stated that nerve-conduction changes at 4 months were not significant. Exact between-group painDETECT values, the same population, dose and relevant denominators are unverified; it was not counted as a direct replication. S05	Favorable symptom results, nerve-conduction results without a significant difference and the reasons for exclusion were preserved together. Replication within the exact boundaries was not verified.	S05 original abstract, population/dose/scale, denominators, duration and results	Compare population, dose, measurements and denominators in the original abstract and full text to distinguish direct replication from adjacent symptom results.
31	Partly verified	Full text not readStored summary read	N31 · 2026 active-dose comparisonIs a comparison of 1000 versus 2000 µg a placebo-controlled replication?Supplementary; required for dose or replication claims	F03's 2026 title compares oral B12 at 1000 µg versus 2000 µg. It has no control without supplementation, and the record states that direct numerical pain results could not be verified from the accessed metadata. It was not counted as a direct replication of the placebo comparison. S06	The active-dose comparison's identity and reason for exclusion as a direct replication were preserved. Exact pain outcomes, population and chemical form were not verified.	S06 population, chemical form, active doses, endpoints, denominators and full results	Compare the original trial's population, chemical form, doses, comparator and endpoints, and assess dose comparison as a separate question.
32	Partly verified	Full text not readStored summary read	N32 · Reviews and discovery leadsAre S11 and S12 being counted as new independent replications?Supplementary; required for claims about overall replication	S11 is retained as a discovery excerpt with failed full-text access, and S12 as discovery metadata for a review/meta-analysis of mixed B-vitamin types, routes and formulations. Neither is counted toward direct effects; no included-study table or exact replication count is newly created here. S11 S12	Discovery identities and historical access limitations were linked. Comparison of included studies and families addressing the same question remains incomplete.	Reviews' included-study tables, original-trial identities, chemical forms/routes/endpoints and duplicate-report linkage	Link the trials included in reviews to original reports, then individually compare family overlap, differences in conditions and unverified results.
33	Partly verified	Full text not readStored summary read	N33 · Funding and independenceWere product supply and no external funding reinterpreted as independent funding?Supplementary; required for independence claims	The original trial retains declarations of no external research funding, in-kind company supply of product and placebo, no company involvement and no conflicts of interest. The original assessment's I1 is not changed to public independent funding I2 or manufacturer-only I0. S01	The reported declarations were linked, but no verification by an independent institution or new exhaustive review of interests was performed.	Research funding, product/placebo supply, company role, COI and institutional/author declarations	Compare funding, supply, company roles and author declarations report by report, recording the scope of verification and omissions.
34	Partly verified	Full text not readStored summary read	N34 · Trial reporting of harmsIs nonreporting of suspected B12-related AEs being read as 0 AEs of any kind?Supplementary; required for safety interpretation	The manuscript retains the report that no suspected B12-related adverse reactions were reported in the limited trial. Group-specific denominators for all AEs/SAEs, collection methods, discontinuations and safety over the long term or in special populations are unverified. This is not reinterpreted as 0 events of any kind or as harm incidence. S01 S07 S08 S09	The narrow scope of the original harms report was preserved. The complete event and discontinuation records, denominators and collection system were not verified.	All AEs, SAEs, relatedness, discontinuations, collection methods, events/people and denominators/duration by group	Compare original safety tables and collection, relatedness and discontinuation records by group to distinguish people, events, duration and unreported information.
35	Met	Full text not readStored summary read	N35 · Official metformin documentIs the safety context of metformin and low B12 an analgesic effect?Supplementary; required for safety and population interpretation	S07 is an MHRA safety document concerning the association between metformin and low B12 and risk monitoring. The retained manuscript uses it as population and safety context, not as evidence for a methylcobalamin pain effect or individual medication changes. S07	The retained role of the official document and the boundaries excluding efficacy claims and personal instructions were verified. The official source text was not read in this exercise.	Population, scope of recommendations and original location in official document S07	Compare the official document's exposure, population and recommendations with the original trial question to distinguish safety context from efficacy claims.
36	Met	Full text not readStored summary read	N36 · Warnings for other chemical formsHas the cobalt warning been repurposed as a methylcobalamin event rate?Supplementary; required for extending harms claims	The MHRA cobalt-sensitivity notice in S08 explicitly names hydroxocobalamin and cyanocobalamin. This warning was not repurposed as harm incidence in the methylcobalamin trial; warnings for other products and individual safety are distinguished. S08	The chemical forms explicitly named in the retained notice and limits on transferring it were verified. This does not mean that methylcobalamin has no allergy risk.	Specified products, chemical forms and scope of sensitivity reactions in official notice S08	Compare the notice's specified chemical forms and reactions with the trial formulation and population to assess the scope of the warning's applicability.
37	Partly verified	Full text not readStored summary read	N37 · UL and reused sourceDoes the ODS statement that no UL is established mean unlimited safety?Supplementary; required for generalizing safety	S09 is a record reusing a citation/safety excerpt from prior record 110, with original verified_date=2026-07-07. NIH's statement that no UL is established is not a guarantee of unlimited safety. The ODS original and prior record 110 file were not read in this exercise; that record was checked only in the current case 3111 summary. S09	The inherited description and historical source were linked. The original ODS text, original bytes of prior record 110 and long-term/special-population safety were not compared in this exercise.	Original S09 ODS text, actual content/review history of the excerpt from prior record 110, and long-term/special-population safety data	Separately compare the original location of the ODS description, the prior excerpt and long-term/special-population harms data to assess how absence of an upper limit can be interpreted.
38	Unverified	Full text not readStored summary read	N38 · Dose, persistence and subgroupsDoes this also answer optimal dose, persistence after stopping and effects in people with normal B12?Supplementary; required for the corresponding extended claims	The selected conditions are 1000 µg/day for 12 months in people with long-term metformin use and low B12. Optimal dose, maintenance after discontinuation and effects in a normal-B12 population are unverified. S06's comparison of different active doses is not automatically used to verify these extensions. S01 S06	The direct evidence required for extensions beyond the selected scope was not verified. No new mandatory conditions were added to the original score comparison.	Direct dose comparisons, follow-up after discontinuation and prespecified interaction results for normal-B12 populations/subgroups	Define dose, post-discontinuation follow-up and subgroup questions separately, then assess the corresponding direct comparisons and interaction results.
39	Not applicable	Full text not readStored summary read	N39 · Other clinical questionsAre NRS, replacement of analgesics and clinical events being required for this score question?Does not apply to the current score question; required for extended claims	Direct results for mean pain NRS/VAS, replacement of analgesics and clinical events are not imposed as additional mandatory conditions for the currently selected painDETECT score question. Those extended efficacy claims were not verified, and the manuscript does not extend the result to a general analgesic effect. S01 S04	A requirement to impose studies of other clinical questions as mandatory for the current narrow score comparison does not apply. This does not eliminate unread or unverified material.	Interpretive boundaries of the selected question and corresponding direct clinical results if the claim is extended	When extending the question to mean pain, medication replacement or clinical events, define and assess separate populations, endpoints, comparators and direct results.
40	Met	Full text not readStored summary read	N40 · Actual readingWere the stored summary, historical full-text reading and current unread status distinguished?Required	What was actually read in this exercise was the Korean text, structure, evidence, citations and historical records in the current case 3111 stored summary. Historical access_level values for the S01 PDF, S04 author-hosted web full text, official/manufacturer documents and other materials are preserved as manuscript records. Access to external originals, the registration, prior record 110, and older ZIP/audit/calculation logs was not attempted in this exercise; they were neither acquired nor read. Report-specific actual access dates are null because the original citations do not provide them. S01 S02 S03 S04 S05 S06 S07 S08 S09 S10 S11 S12	The distinction between actual summary reading and historical/current access to each material was documented. External source content was not newly verified.	Exact locations in retained summaries, physical material types, historical access, current acquisition/reading and dates	Record each material's identity, original location, access events and acquisition/reading separately, and distinguish summary links from external links when comparing them.
41	Partly verified	Full text not readStored summary read	N41 · Scope of searches and correctionsIs the review of 2026-09-16 being read as a current exhaustive search?Required	The evidence reference date is 2026-09-16, and the review date for this conversion is 2026-10-05. evidence_status records verification of direct human evidence and eligible comparisons within the historical ChatGPT search scope, but absence_proven is false. The current corrections list is empty; no new search or correction/retraction lookup was performed in this exercise. S01 S03 S05 S06 S11 S12	The historical search scope and current conversion scope were linked, but no current exhaustive search or correction check was performed.	Historical search scope, list of unverified matters, correction/retraction records and reasons for updates	During an authorized update, compare the historical search scope with the scope of new materials, and link corrections, retractions and unpublished/registered records to original reports.
42	Met	Full text not readStored summary read	N42 · Original verdict and historical calculationsHave C, 46 and the existing EX/CX been turned into verdicts produced by this new table?Required (to preserve the original verdict)	The original verdict is C, 46 points, with B/P/R1/I1/EX/B2/CX. The manuscript's reruns of the calculator and scoring table are historical records; they were not rerun in this exercise. formal_adjusted_CI and some auxiliary axis fields are null, not 0. The existing −2.9/−3.8 are historical descriptive values; this table creates no new grade, effect or score.	The original values, the historical nature of the calculations and the meaning of null values were preserved. No clinical reassessment or official methodological certification was performed.	Original grade, score, axes, null values, sources of existing calculations and reasons for unverified information	Preserve the original assessment inputs, historical calculations and correction records to distinguish original values from new evidence events, and compare before and after an authorized revision.
43	Partly verified	Full text not readStored summary read	N43 · Publication metadata and updatesIs historical deployment metadata being read as completed publication of this table?Required (for tracking events)	The original first_published_at is null and publication_status is ready_with_uncertainty. The record also contains server_deployed=true, server_write_performed=false and deployed_at=2026-09-16. These different historical metadata statements are not read as completed public release of the current table; original values and the policy of revisions under the same ID/URL are preserved.	The original metadata statements and event boundaries were linked. Actual historical deployment receipts and website publication in this exercise were not verified.	Original ID, canonical URL, initial-publication/server metadata and revision policy/history	Compare receipts for each publication event and actual public-release times with original metadata and revision history, preserving the full before-and-after content under the same ID/URL.

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43 itemsWhat the statuses mean

Assessment scope

Stored-material review date: 2026-10-05
Original evidence cut-off: 2026-09-16
Scope actually checked: Stored Korean and English manuscripts and case-specific criteria and application records. Full papers, supplements, registrations, plans and original data were not read.
What the dates mean: This is the date the stored materials were checked, not the date of an up-to-date clinical literature search.
Population: Adults with type 2 diabetes and confirmed peripheral and autonomic neuropathy; metformin for ≥4 years, B12 <400 pmol/L; stable HbA1c of 6.5–7.5%; pain threshold for entry unverified
Ingredient, formulation and route: Methylcobalamin (mecobalamin), vitamin B12 as the single added active ingredient · B12 fix, UNI-PHARMA; oral dispersible tablet. Historical trial batch and placebo excipients unverified · Oral dispersible formulation; no sublingual holding time is inferred and no injection route is substituted
Dose: 1000 µg, 1 time daily; total product intake and dietary exposure unverified
Comparator: Similar-looking placebo; stable common glycemic management, restrictions on other analgesics and occasional paracetamol permitted
Measured outcome: Primary endpoint selected for this page: between-group comparison of change in reported painDETECT score at 12 months; whether it was the registered primary (1st) endpoint is unverified
Duration: 12 months
Questions outside this scope: Mean pain NRS/VAS; Analgesic efficacy in diabetic neuropathy generally; Supplementation in all patients with absolute deficiency or normal B12; Optimal dose and persistence after discontinuation; Replacement of analgesics and prevention of clinical events; Efficacy of other cobalamins, injections or multicomponent products; Independent determination of harm incidence or causality

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 · Didangelos et al. 2021. Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial

Source

Material type: Decisive original trial
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: Of 90 participants, 44 were allocated to methylcobalamin and 46 to placebo, and all reportedly completed the trial. painDETECT scores were 18.4→17.1 versus 19.3→20.9; the comparison adjusted for HbA1c and glycemic medications reported P<0.001. The existing simple change contrast of −2.9 points and endpoint difference of −3.8 points are unadjusted descriptive values; the adjusted coefficient, SE, CI and endpoint-specific denominators are unverified. MNSIE P=0.607, HbA1c P=0.876 and the baseline SD conflict of 9.2/9.7 are also preserved.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full article text in PDF Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

S02 · Didangelos et al. — NLM bibliographic record

Source

Material type: Bibliographic record and abstract of the same original article
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: This NLM record corresponds to S01 through DOI 10.3390/nu13020395, PMID 33513879 and PMCID PMC7912007. As a discovery source, it was not counted toward direct effects, and this stored summary contains no separate detailed results specific to S02.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic record and abstract Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

S03 · ClinicalTrials.gov NCT04706377

Source

Material type: Registration identity of the same original trial
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: Registration number NCT04706377 was linked. Historical registration_shell_only access and the unverified initial posting, amendment history, pain-endpoint hierarchy and protocol/SAP are retained. Registration identity is not an independent replication or a completed result.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full web clinical-trial registration record Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

S04 · Freynhagen et al. 2006. painDETECT: a new screening questionnaire to detect neuropathic components in patients with back pain

Source

Material type: Scale-definition report
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: The original paper-form painDETECT total score has a range of −1–38 and sums sensory qualities, pain course and radiation. Items recording pain intensity are not included in the total score. The trial's exact language, version, recall period and MCID remain separately unverified. Historical rejection of access to the publisher PDF and reading of the author-hosted web full text were not actions performed in this exercise.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full original article text on the author's website Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.
Publisher's full article text in PDF Material URL unverified	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

S05 · Yaqub, Siddique, Sulimani. 1992. Effects of methylcobalamin on diabetic neuropathy

Source

Material type: Adjacent methylcobalamin trial
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: The 1992 abstract reported improvement in somatic and autonomic symptoms, but stated that nerve-conduction changes at 4 months were not significant. Between-group values for the selected painDETECT score, the same population, dose and relevant denominators are unverified.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic record and abstract Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

S06 · Mansour et al. 2026. Efficacy of Oral Vitamin B-12 at 1000 micrograms Compared with 2000 micrograms on Neuropathic Outcomes

Source

Material type: Adjacent oral-B12 active-dose trial
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: The 2026 title is an active-dose comparison of oral B12 at 1000 µg versus 2000 µg. It has no control without supplementation, and direct numerical pain results could not be verified from the accessed metadata. The original full text, chemical form, exact endpoint and correspondence of the population are not filled in from the title alone.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic record and search-result title Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.
Publisher's full article text Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

S07 · MHRA. Metformin and reduced vitamin B12 levels: new advice for monitoring patients at risk

Source

Material type: Official safety notice
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: This is the MHRA monitoring and risk-factor document dated 2022-06-20. The association between metformin and low B12 provides population and safety context; it is not used as evidence for a methylcobalamin pain effect or individual medication changes.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full official safety notice on the web Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

S08 · MHRA. Vitamin B12 (hydroxocobalamin, cyanocobalamin): cobalt sensitivity reactions

Source

Material type: Official safety notice for other chemical forms
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: The MHRA cobalt-sensitivity notice dated 2023-12-18 explicitly names hydroxocobalamin and cyanocobalamin. It is not repurposed as harm incidence in the methylcobalamin trial or as individual safety.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full official safety notice on the web Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

S09 · NIH ODS. Vitamin B12: Fact Sheet for Health Professionals — supplied record 110 citation

Source

Material type: Prior excerpt from an official fact sheet
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: This is NIH ODS's description that no UL is established, inherited from citations/6 and a safety excerpt in prior record 110. The original verified_date=2026-07-07 is not an access date. The statement that no upper limit is established is not reinterpreted as unlimited safety of long-term high doses or in all special populations. Prior record 110 and the external ODS original were not read in this exercise.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full fact sheet on the web Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.
Excerpted citation from the stored summary of prior record 110 Material URL unverified	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

S10 · UNI-PHARMA. B12 fix product and food-supplement catalogue

Source

Material type: Manufacturer's product description
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: The conflict between 1000 µg/1000 mg labeling on the current manufacturer page is preserved as unresolved. The trial dose is 1000 µg/day from S01; the current product page does not establish the historical trial batch.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full manufacturer's product description on the web Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.
Manufacturer's food-supplement catalogue (file format unverified) Material URL unverified	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

S11 · Jayabalan et al. 2016. Vitamin B supplementation for diabetic peripheral neuropathy

Source

Material type: Discovery identity of a related review
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: A discovery excerpt from the related 2016 review and failure to access its full text directly at that time were recorded. The current stored summary lacks detailed included studies and results; exact independent replications and effect values are not filled in.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full review article text Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

S12 · Mandra et al. 2026. Vitamin B Supplementation for Diabetic Peripheral Neuropathy: A Review and Meta-Analysis

Source

Material type: Discovery identity of a mixed-B-vitamin meta-analysis
Materials actually read: Retained summary read; access to the external or separate original materials was not attempted in this exercise, and they were neither acquired nor read
Findings recorded in the stored summary: The historical verification locations for the 2026 review/meta-analysis are the publisher's search results and an abstract reproduction including the authors' references. It concerns mixed B-vitamin types, routes and formulations; the current stored summary lacks a detailed included-study table and values for the selected score. No direct replications are added.
Record level: A summary based on reading actual results/attribution and the limits of retained detail in the current case 3111 retained summary. It is not a reading of the original document in this exercise or a new result.
Study overlap and independent replication: The original trial, reports/registration of the same trial, scale, official/manufacturer sources, discovery reviews and adjacent F02/F03 were distinguished. No new unique-trial count was generated automatically.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full review article text Open material ↗	Unverified (only retained historical access is linked; no lookup in this exercise)	Not attempted in this exercise	Not read	The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.

Report counts versus independent study counts

These are the report linkages in the stored manuscript. F01: original trial, NLM record and registration identity; reports from the same family, not 3 independent replications (S01, S02, S03) / F02: adjacent 1992 trial; 4-month nerve-conduction results and different symptoms/dose; not counted as a direct replication (S05) / F03: 2026 active-dose comparison; differs from a placebo control without supplementation; not counted as a direct replication (S06). Nontrial reports: S04, S07, S08, S09, S10, S11, S12. The retained manuscript records 1 core trial family, while the total number of unique trials and total number of participants are unverified. F01/F02/F03 preserve the study_id values in the original evidence. No new unique-trial count or total participant sum was produced, and overlap in reviews was not established.

Review criteria

Version NGM-v3111-METHYL-B12-METFORMIN-PAINDETECT12M-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 and which 12-month score are being compared?

Required materials and conditions: The original question and specifications of the population, ingredient, route, dose, comparator, time point and endpoint
Conditions for verification: Link the population, methylcobalamin, placebo and 12-month painDETECT comparison in the original /ko/effect and fixed question.
Requirement and applicability: Required
Application exceptions: The actual subclaims list is empty. Mean pain NRS, all diabetic neuropathy and replacement of analgesics are not added as new subclaims.
Why this condition is needed: The B12 effects discussed across the page must be distinguished from the selected score comparison.
Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed — An internally developed, item-specific adaptation for Separate question. No official methodological tool was applied or certification performed.

N02 · Was methylcobalamin the trial's single active ingredient?

Required materials and conditions: The original trial's active ingredient, chemical form and whether it was a combination product
Conditions for verification: Identify methylcobalamin/mecobalamin as the actual added ingredient and distinguish it from other cobalamins.
Requirement and applicability: Required
Application exceptions: Cyanocobalamin, hydroxocobalamin and B-vitamin combinations are not direct evidence for this single-ingredient methylcobalamin comparison.
Why this condition is needed: Needed to avoid combining effects of different chemical forms or combination products solely on the basis of the name B12.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed — An internally developed, item-specific adaptation for Active ingredient. No official methodological tool was applied or certification performed.

N03 · Do the supply identity and historical batch of B12 fix match?

Required materials and conditions: Trial-product supply records, batch/purity documentation and the current product description
Conditions for verification: Record the trial product name and supplier, the current manufacturer description, and historical batch and purity separately.
Requirement and applicability: Required
Application exceptions: Linking the UNI-PHARMA name and B12 fix page does not independently confirm the historical batch, purity or efficacy.
Why this condition is needed: Needed to avoid treating the current product page as verification of the historical trial batch.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed — An internally developed, item-specific adaptation for Trial product. No official methodological tool was applied or certification performed.

N04 · Has the oral dispersible formulation been reinterpreted as sublingual or injectable?

Required materials and conditions: Trial administration method and oral dispersible formulation specifications
Conditions for verification: Preserve the actual oral dispersible formulation and route without filling in an unreported sublingual holding time.
Requirement and applicability: Required
Application exceptions: Do not add a sublingual holding time, injection route or absorption mechanism absent from the source material.
Why this condition is needed: A formulation that disperses in the mouth cannot be assumed to have the same administration route as sublingual holding or injection.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed — An internally developed, item-specific adaptation for Route of administration. No official methodological tool was applied or certification performed.

N05 · Has the trial dose been distinguished from total exposure?

Required materials and conditions: Trial dose and frequency, dietary/additional supplementation exposure and adherence records
Conditions for verification: Distinguish the trial dose of 1000 µg 1 time daily from total exposure including diet and additional supplementation.
Requirement and applicability: Required
Application exceptions: 1000 µg/day is a trial condition, not an instruction for personal use or a change in diabetes medication.
Why this condition is needed: Needed to avoid turning the trial's nominal dose into an individual dosing instruction or actual total intake.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Nominal dose. No official methodological tool was applied or certification performed.

N06 · Has the manufacturer's 1000 µg versus 1000 mg labeling been resolved?

Required materials and conditions: Locations of the manufacturer's labels, corrections and contemporaneous trial-dose documentation
Conditions for verification: Preserve both printed units on the current product page and handle them separately from the trial dose.
Requirement and applicability: Required
Application exceptions: The conflict on the current product page does not justify changing the original trial's 1000 µg/day to 1000 mg/day.
Why this condition is needed: Needed to avoid silently harmonizing conflicting product units or substituting them for the trial dose.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Conflicting product units. No official methodological tool was applied or certification performed.

N07 · Has 12-month administration been separated from results over other durations?

Required materials and conditions: Trial administration and assessment times, and the duration of each adjacent study
Conditions for verification: Link the selected score's 12-month time point and administration period without combining the adjacent 4-month result with it.
Requirement and applicability: Required
Application exceptions: The 4-month nerve-conduction result in S05 is a different outcome from this 12-month painDETECT comparison.
Why this condition is needed: Studies cannot be counted as direct replications when durations and measurements differ, even if they use the same neuropathy label.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed — An internally developed, item-specific adaptation for Observation period. No official methodological tool was applied or certification performed.

N08 · Which adults with diabetic neuropathy were selected?

Required materials and conditions: Population diagnoses, duration of metformin use and B12 eligibility criterion
Conditions for verification: Link the actual selection criteria: type 2 diabetes, confirmed peripheral and autonomic neuropathy, metformin for ≥4 years and low B12.
Requirement and applicability: Required
Application exceptions: Do not extend the selected population with low B12 and long-term metformin use to diabetes generally or to populations with normal B12.
Why this condition is needed: Needed to avoid automatically applying the results to all patients with diabetic neuropathy.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed — An internally developed, item-specific adaptation for Population selection. No official methodological tool was applied or certification performed.

N09 · Is B12 <400 pmol/L being interpreted as absolute deficiency in everyone?

Required materials and conditions: Baseline B12 criterion, diagnosis of deficiency and population-specific results
Conditions for verification: Distinguish the trial's low-B12 criterion from confirmed absolute deficiency and the effects of supplementation in people with normal B12.
Requirement and applicability: Required
Application exceptions: Do not classify every participant as having confirmed absolute deficiency solely on the basis of B12 <400 pmol/L.
Why this condition is needed: A low eligibility value and correction of confirmed deficiency are different questions of applicability.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed — An internally developed, item-specific adaptation for Low-B12 boundary. No official methodological tool was applied or certification performed.

N10 · Were the pain NRS entry threshold and minimum duration verified?

Required materials and conditions: Pain diagnosis, entry NRS criterion and minimum duration in the eligibility documentation
Conditions for verification: Distinguish the description of painful neuropathy from the verification status of the exact pain threshold and duration for entry.
Requirement and applicability: Required
Application exceptions: Do not reinterpret unverified entry criteria as a population without pain or absence of analgesic efficacy.
Why this condition is needed: The description 'painful' alone does not establish a population with a particular pain intensity or duration of chronic pain.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Pain entry criteria. No official methodological tool was applied or certification performed.

N11 · Was selection for stable HbA1c of 6.5–7.5% preserved?

Required materials and conditions: Baseline glycemic status, stability criteria and glycemic-medication records by group
Conditions for verification: Link the stable HbA1c range with the population receiving common glycemic management.
Requirement and applicability: Required
Application exceptions: A nonsignificant result for HbA1c change is not a direct substitute for this stable-range selection criterion or the painDETECT result.
Why this condition is needed: Needed to avoid applying the result of adjunctive treatment on stable glycemic management to all glycemic states.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Glycemic-status selection. No official methodological tool was applied or certification performed.

N12 · Was the full composition of the similar-looking placebo verified?

Required materials and conditions: Placebo appearance, composition and batch, and common management in each group
Conditions for verification: Record the similar-looking placebo comparison separately from the unverified full excipient composition.
Requirement and applicability: Required
Application exceptions: Do not conclude that the placebo was an active treatment or that blinding was broken because its full composition is unverified.
Why this condition is needed: Needed to avoid confusing similar appearance with complete placebo identity or biological inactivity.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Placebo specifications. No official methodological tool was applied or certification performed.

N13 · Were common glycemic management and adjustment variables distinguished?

Required materials and conditions: Glycemic medications and management changes by group, and ANCOVA adjustment specifications
Conditions for verification: Record the common management policy, actual treatment changes by group, and adjustment for HbA1c/glycemic medications separately.
Requirement and applicability: Required
Application exceptions: Do not indicate that all differences in concomitant treatment, confounding and adherence were resolved merely because adjustment variables were used.
Why this condition is needed: Needed to avoid using a common policy as proof that all actual treatments were identical.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Common treatment. No official methodological tool was applied or certification performed.

N14 · Is the policy permitting paracetamol the same as actual use?

Required materials and conditions: Rescue-analgesic policy, amount used and changes by group, and handling in the analysis
Conditions for verification: Distinguish restrictions on other analgesics and occasional paracetamol permitted for 2–3 days from the actual amounts used by group.
Requirement and applicability: Required
Application exceptions: Do not interpret the policy restricting analgesics as an effect replacing analgesics, or fill in actual use as 0.
Why this condition is needed: A permission rule alone cannot establish that actual analgesic exposure was identical between groups.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Rescue analgesics. No official methodological tool was applied or certification performed.

N15 · Were numerical adherence and additional B12 exposure verified?

Required materials and conditions: Dosing records and numerical adherence by group, and records of diet, fortified foods and additional supplementation
Conditions for verification: Distinguish nominal administration from actual dosing, diet, fortified foods and other supplementation exposure.
Requirement and applicability: Required
Application exceptions: Do not substitute 90 fully adherent participants or identical total intake for the 90 reported completers.
Why this condition is needed: Needed because reported completion by everyone differs from actual adherence.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Adherence and diet. No official methodological tool was applied or certification performed.

N16 · Is the painDETECT total score a mean pain-intensity NRS?

Required materials and conditions: Original scale definition, total-score components, range and direction
Conditions for verification: Distinguish the screening composite of sensory qualities, pain course and radiation from items recording pain intensity.
Requirement and applicability: Required
Application exceptions: Preserve the scale's original screening purpose while retaining the comparison of the patient-reported score itself selected for this page.
Why this condition is needed: Needed to avoid elevating a screening total score to a reduction in mean pain NRS/VAS.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4; internally defined boundaries for extending the claim — An internally developed, item-specific adaptation for Scale definition. No official methodological tool was applied or certification performed.

N17 · Were the trial questionnaire's language, version and recall period verified?

Required materials and conditions: Trial questionnaire, language/translation, version, recall period and scoring procedure
Conditions for verification: Distinguish the original scale description from the verification status of the language, version and recall period actually used in the trial.
Requirement and applicability: Required
Application exceptions: Do not infer the trial questionnaire version or recall period from the original scale's total-score range.
Why this condition is needed: The original scale definition does not verify all aspects of how measurement was actually implemented in the trial.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Questionnaire implementation. No official methodological tool was applied or certification performed.

N18 · Was the page's primary endpoint at 12 months distinguished from a registered primary (1st) endpoint?

Required materials and conditions: Outcome time points, original registration hierarchy, initial posting and amendment history
Conditions for verification: Record the reported score at 12 months selected for this page separately from the verification status of the preregistered primary endpoint.
Requirement and applicability: Required
Application exceptions: Do not reinterpret an unverified registration hierarchy as confirmed absence of registration or confirmed selective reporting.
Why this condition is needed: Needed to avoid automatically turning the page's primary endpoint into a preregistered primary (1st) outcome.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application — An internally developed, item-specific adaptation for Selected time point. No official methodological tool was applied or certification performed.

N19 · Was the RCT designation distinguished from implementation of allocation concealment?

Required materials and conditions: Original trial design, allocation/concealment, implementation of blinding and baseline data
Conditions for verification: Link the randomized, placebo-controlled, double-blind design and the unreported implementation of allocation concealment to each outcome.
Requirement and applicability: Required
Application exceptions: Do not present unreported implementation of allocation concealment as actual concealment failure or an established magnitude of bias.
Why this condition is needed: Needed because a design designation alone cannot establish absence of allocation or measurement bias.
Referenced methods: M08 §8.1–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Allocation and blinding. No official methodological tool was applied or certification performed.

N20 · Are allocation of 90 participants, 44/46 by group, and completion being read as analysis denominators?

Required materials and conditions: Flow diagram and denominators for allocation, completion, measurement and analysis by group
Conditions for verification: Preserve allocation and reported completion of 44/46 separately from endpoint-specific analysis denominators.
Requirement and applicability: Required
Application exceptions: Do not treat the 90 reported completers as a verified painDETECT analysis n=90 or group-specific n=44/46.
Why this condition is needed: Needed to avoid automatically using a statement that everyone completed the trial as the analysis denominator for each outcome.
Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Allocation and completion. No official methodological tool was applied or certification performed.

N21 · Were the painDETECT analysis population and missing-data handling verified?

Required materials and conditions: PainDETECT analysis denominators by group, analysis population, reasons for missing data/exclusions and their handling
Conditions for verification: Distinguish endpoint-specific analysis populations, ITT/PP and missing-data handling from reported completion.
Requirement and applicability: Required
Application exceptions: Do not arbitrarily label an unreported analysis population as ITT/PP or fill in dropouts and missing data as 0.
Why this condition is needed: Needed to avoid filling in absent analysis populations and denominators as ITT or all completers.
Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Analysis population and missing data. No official methodological tool was applied or certification performed.

N22 · Are the original scores, existing change contrast and endpoint difference being read as the same estimate?

Required materials and conditions: Scores and time points in the original results table, definitions of existing descriptive differences and adjusted results
Conditions for verification: Preserve 18.4→17.1 versus 19.3→20.9 and the manuscript's descriptive values of −2.9/−3.8 separately.
Requirement and applicability: Required
Application exceptions: Do not present the existing −2.9 and −3.8 as new calculations or unreported adjusted estimates.
Why this condition is needed: Needed to avoid confusing within-group change, between-group difference in change, endpoint difference and an adjusted coefficient.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Original scores and descriptive differences. No official methodological tool was applied or certification performed.

N23 · Has P<0.001 been turned into an adjusted coefficient, SE or CI?

Required materials and conditions: ANCOVA specifications, adjusted coefficient, SE, CI, denominators and results table
Conditions for verification: Link the formal ANCOVA comparison of change, adjustment variables and reported P separately from the unreported coefficient/SE/CI.
Requirement and applicability: Required
Application exceptions: P<0.001 is not an exact P value; no adjusted CI or standardized effect is newly back-calculated.
Why this condition is needed: Needed to avoid establishing effect magnitude or precision from statistical significance alone.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application — An internally developed, item-specific adaptation for Adjusted effect and interval. No official methodological tool was applied or certification performed.

N24 · Have the baseline SD values of 9.2 and 9.7 been silently harmonized?

Required materials and conditions: Locations of baseline SD in the original Table 4 and text, corrections, and group/time-point specifications
Conditions for verification: Retain the conflict between the two baseline SD values reported in the retained manuscript and their unresolved attribution.
Requirement and applicability: Required
Application exceptions: Preserve only the recorded conflict of 9.2 versus 9.7 without filling in table cells or group attribution absent from the current stored summary.
Why this condition is needed: Needed to avoid arbitrarily selecting or correcting conflicting variability values, or using them as established inputs for a CI calculation.
Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Conflicting baseline SD. No official methodological tool was applied or certification performed.

N25 · Is there an applicable MCID for painDETECT change in this population?

Required materials and conditions: Evidence for an MCID applicable to this population, scale version and change estimate
Conditions for verification: Distinguish a criterion for an important difference applicable to the selected score, population and time point from a diagnostic screening threshold.
Requirement and applicability: Required (for interpreting clinical importance)
Application exceptions: Do not turn a screening total-score threshold into an MCID or substitute thresholds from another disease or language. Do not reassess the original EX solely because an MCID is absent.
Why this condition is needed: Needed to avoid elevating a statistically significant score difference to a clinically important mean analgesic effect.
Referenced methods: M15 §15.3.1–15.3.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Clinical importance. No official methodological tool was applied or certification performed.

N26 · Was the identity of NCT04706377 distinguished from reading its content?

Required materials and conditions: Original registration record, initial posting, amendment history and outcome hierarchy
Conditions for verification: Distinguish linking a registration number from obtaining the initial posting, amendment history and readable endpoint hierarchy.
Requirement and applicability: Required
Application exceptions: Do not present historical access classified as registration_shell_only as reading the full registration or as confirmation that the trial was unregistered.
Why this condition is needed: Needed to avoid turning the existence of a registration number into verification of a prespecified primary (1st) endpoint or registration timing.
Referenced methods: M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application — An internally developed, item-specific adaptation for Registration history. No official methodological tool was applied or certification performed.

N27 · Were the protocol and SAP compared with the selection of actual results?

Required materials and conditions: Protocol, SAP, prespecified endpoints/analyses/time points, handling of multiple endpoints and reporting
Conditions for verification: Distinguish unavailable plans and unverified multiple-endpoint handling and prespecified hierarchy from confirmed selective reporting.
Requirement and applicability: Required
Application exceptions: Do not treat unavailable materials as confirmation of selective reporting or arbitrarily fill in primary_failed_secondary_positive as true/false.
Why this condition is needed: Needed to expose the lack of materials for assessing whether only favorable scores were selected.
Referenced methods: M08 Table 8.2.a, M04 §4.6.3; internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Plans and multiple endpoints. No official methodological tool was applied or certification performed.

N28 · Were nonsignificant results for MNSIE and HbA1c preserved?

Required materials and conditions: All reported endpoints, denominators, time points and analyses, including favorable results and results without a significant difference
Conditions for verification: Attribute P=0.607 and P=0.876 to their other endpoints separately from the selected painDETECT outcome.
Requirement and applicability: Required
Application exceptions: Do not reinterpret nonsignificance as an effect of 0, equivalence or direct refutation of the painDETECT result.
Why this condition is needed: Other endpoints without a significant difference must be preserved alongside favorable scores, rather than retaining only favorable scores.
Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed — An internally developed, item-specific adaptation for Results without a significant difference. No official methodological tool was applied or certification performed.

N29 · Are S01, S02 and S03 being counted as three replications?

Required materials and conditions: DOI, PMID, PMCID, registration number and report-family linkage
Conditions for verification: Link the original trial, NLM bibliographic record and registration number within F01, distinguishing them from independent replication.
Requirement and applicability: Required
Application exceptions: Do not delete bibliographic/registration records because they lack separate results, or add linked records as new independent trials.
Why this condition is needed: Needed to avoid converting the number of article, bibliographic and registration reports into a count of unique trials.
Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Same-trial family. No official methodological tool was applied or certification performed.

N30 · Are improvement and the absence of a significant nerve-conduction difference in S05 being read as replication of the same question?

Required materials and conditions: S05 original abstract, population/dose/scale, denominators, duration and results
Conditions for verification: Record F02's symptom improvement and nonsignificant nerve-conduction result at 4 months alongside the unverified selected score, population and dose.
Requirement and applicability: Supplementary; required for a claim of exact replication
Application exceptions: Do not substitute nonsignificant nerve-conduction results at 4 months for no effect on the selected 12-month painDETECT outcome.
Why this condition is needed: Needed to avoid creating an exact painDETECT replication from favorable related symptom results alone.
Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Adjacent 1992 trial. No official methodological tool was applied or certification performed.

N31 · Is a comparison of 1000 versus 2000 µg a placebo-controlled replication?

Required materials and conditions: S06 population, chemical form, active doses, endpoints, denominators and full results
Conditions for verification: Distinguish F03's comparison of two active doses from a placebo comparison without supplementation, without filling in unverified pain values.
Requirement and applicability: Supplementary; required for dose or replication claims
Application exceptions: Do not automatically establish that oral B12 in the title means the exact methylcobalamin form, the same painDETECT endpoint or the same population.
Why this condition is needed: A comparison of two active doses differs from the efficacy question of added B12 versus no supplementation.
Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed — An internally developed, item-specific adaptation for 2026 active-dose comparison. No official methodological tool was applied or certification performed.

N32 · Are S11 and S12 being counted as new independent replications?

Required materials and conditions: Reviews' included-study tables, original-trial identities, chemical forms/routes/endpoints and duplicate-report linkage
Conditions for verification: Distinguish review identities used for discovery from comparison of the actual inclusion and results of independent original trials.
Requirement and applicability: Supplementary; required for claims about overall replication
Application exceptions: Do not use reviews of mixed B-vitamin types, routes and formulations as direct results for a single-ingredient methylcobalamin painDETECT comparison.
Why this condition is needed: Needed to avoid adding discovery citations to the number of independent trials addressing the same question.
Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Reviews and discovery leads. No official methodological tool was applied or certification performed.

N33 · Were product supply and no external funding reinterpreted as independent funding?

Required materials and conditions: Research funding, product/placebo supply, company role, COI and institutional/author declarations
Conditions for verification: Preserve separately the scope of declarations of no external research funding, company product/placebo supply, no involvement and no COI.
Requirement and applicability: Supplementary; required for independence claims
Application exceptions: Do not use company supply as an automatic reason for exclusion or infer public independent funding I2 or manufacturer-only I0 from no external funding.
Why this condition is needed: Needed to avoid confusing in-kind product supply with funding and independent replication.
Referenced methods: Chamgap's own criteria for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items — An internally developed, item-specific adaptation for Funding and independence. No official methodological tool was applied or certification performed.

N34 · Is nonreporting of suspected B12-related AEs being read as 0 AEs of any kind?

Required materials and conditions: All AEs, SAEs, relatedness, discontinuations, collection methods, events/people and denominators/duration by group
Conditions for verification: Distinguish the report that no suspected B12-related adverse reactions were observed from all AEs/SAEs, discontinuations, denominators and the scope of collection.
Requirement and applicability: Supplementary; required for safety interpretation
Application exceptions: Do not substitute 0 AEs, SAEs or discontinuations for the report that everyone completed the trial, or newly calculate event rates.
Why this condition is needed: Needed to avoid turning limited reporting of relatedness into absence of all events or verified safety.
Referenced methods: M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed differentiation is internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application — An internally developed, item-specific adaptation for Trial reporting of harms. No official methodological tool was applied or certification performed.

N35 · Is the safety context of metformin and low B12 an analgesic effect?

Required materials and conditions: Population, scope of recommendations and original location in official document S07
Conditions for verification: Distinguish the MHRA risk-monitoring context from efficacy of the selected methylcobalamin intervention and individual medication changes.
Requirement and applicability: Supplementary; required for safety and population interpretation
Application exceptions: Do not use the official monitoring document to justify a methylcobalamin painDETECT effect or an individual change in metformin.
Why this condition is needed: Needed to avoid reversing an association between medication and B12 status into an analgesic effect of supplementation.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied — An internally developed, item-specific adaptation for Official metformin document. No official methodological tool was applied or certification performed.

N36 · Has the cobalt warning been repurposed as a methylcobalamin event rate?

Required materials and conditions: Specified products, chemical forms and scope of sensitivity reactions in official notice S08
Conditions for verification: Preserve the chemical-form and event scope of the warning explicitly naming hydroxocobalamin and cyanocobalamin.
Requirement and applicability: Supplementary; required for extending harms claims
Application exceptions: Do not turn a cobalt-sensitivity warning into confirmation that methylcobalamin is risk-free, or that causality or frequency of harm is established.
Why this condition is needed: Needed to avoid transferring warnings for other cobalamins to harm incidence in this trial or individual safety.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied — An internally developed, item-specific adaptation for Warnings for other chemical forms. No official methodological tool was applied or certification performed.

N37 · Does the ODS statement that no UL is established mean unlimited safety?

Required materials and conditions: Original S09 ODS text, actual content/review history of the excerpt from prior record 110, and long-term/special-population safety data
Conditions for verification: Distinguish the inherited UL description and source-material review date from prior record 110 from actual reading in the current exercise.
Requirement and applicability: Supplementary; required for generalizing safety
Application exceptions: Do not present the review date 2026-07-07 from prior record 110 as the actual access date of S09 or the date of reading ODS in this exercise.
Why this condition is needed: Needed because absence of a UL differs from a guarantee of safety at high doses, over the long term or in all populations.
Referenced methods: M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied — An internally developed, item-specific adaptation for UL and reused source. No official methodological tool was applied or certification performed.

N38 · Does this also answer optimal dose, persistence after stopping and effects in people with normal B12?

Required materials and conditions: Direct dose comparisons, follow-up after discontinuation and prespecified interaction results for normal-B12 populations/subgroups
Conditions for verification: Distinguish 1000 µg/day for 12 months in the selected low-B12 population from extensions concerning dose, post-discontinuation follow-up and normal B12.
Requirement and applicability: Supplementary; required for the corresponding extended claims
Application exceptions: Do not make every dose, discontinuation or normal-B12 study mandatory for the narrow original question. Do not determine an optimal dose solely from S06's active-dose title.
Why this condition is needed: Needed to avoid extending the main effect to an optimal dose, permanent effect or effects at all B12 levels.
Referenced methods: M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed; M03 §3.2.1; detailed population criteria are internally designed — An internally developed, item-specific adaptation for Dose, persistence and subgroups. No official methodological tool was applied or certification performed.

N39 · Are NRS, replacement of analgesics and clinical events being required for this score question?

Required materials and conditions: Interpretive boundaries of the selected question and corresponding direct clinical results if the claim is extended
Conditions for verification: Distinguish the selected painDETECT score itself from separate questions about mean pain NRS, replacement of analgesics and clinical events.
Requirement and applicability: Does not apply to the current score question; required for extended claims
Application exceptions: Does not apply does not mean that other clinical outcomes were verified. Mean pain intensity and replacement of analgesics remain unverified.
Why this condition is needed: Needed to avoid unconditionally requiring studies of other clinical questions for the narrow score question.
Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim — An internally developed, item-specific adaptation for Other clinical questions. No official methodological tool was applied or certification performed.

N40 · Were the stored summary, historical full-text reading and current unread status distinguished?

Required materials and conditions: Exact locations in retained summaries, physical material types, historical access, current acquisition/reading and dates
Conditions for verification: Separate actual reading of the current stored summary from each material's historical access, lack of original bytes and unattempted access in this exercise.
Requirement and applicability: Required
Application exceptions: Leave missing report-specific access dates null. Do not infer access dates from the global verified_date.
Why this condition is needed: Needed to avoid upgrading full-text access recorded in an original citation to full-text reading in this exercise.
Referenced methods: M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design — An internally developed, item-specific adaptation for Actual reading. No official methodological tool was applied or certification performed.

N41 · Is the review of 2026-09-16 being read as a current exhaustive search?

Required materials and conditions: Historical search scope, list of unverified matters, correction/retraction records and reasons for updates
Conditions for verification: Distinguish the evidence reference date, the review date for this conversion, the historical search scope and the absence of a new search.
Requirement and applicability: Required
Application exceptions: Do not present the absence of a new search as proof of 0 studies, an effect of 0 or no new corrections.
Why this condition is needed: Needed to avoid exaggerating a check of stored materials into a current search of all literature or a guarantee of completeness.
Referenced methods: M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Scope of searches and corrections. No official methodological tool was applied or certification performed.

N42 · Have C, 46 and the existing EX/CX been turned into verdicts produced by this new table?

Required materials and conditions: Original grade, score, axes, null values, sources of existing calculations and reasons for unverified information
Conditions for verification: Preserve the original grade/score, 7 axes, null values and references to existing calculations, distinguishing them from statuses in the unscored evidence-gap table.
Requirement and applicability: Required (to preserve the original verdict)
Application exceptions: Do not rerun the original calculator or precedents in this exercise. Link the original C, 46, EX, CX and null values only as historical source values.
Why this condition is needed: Needed to avoid automatically carrying the existing assessment over as new table scores, efficacy probabilities or fulfillment of criteria.
Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design — An internally developed, item-specific adaptation for Original verdict and historical calculations. No official methodological tool was applied or certification performed.

N43 · Is historical deployment metadata being read as completed publication of this table?

Required materials and conditions: Original ID, canonical URL, initial-publication/server metadata and revision policy/history
Conditions for verification: Distinguish events in the existing ID/URL and publication/server metadata from this creation and future website posting.
Requirement and applicability: Required (for tracking events)
Application exceptions: Do not arbitrarily correct original values such as server_deployed=true, server_write_performed=false and first_published_at=null. For this creation, published is false.
Why this condition is needed: Needed to avoid using historical metadata statements as evidence of public release in this exercise.
Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design — An internally developed, item-specific adaptation for Publication metadata and updates. No official methodological tool was applied or certification performed.

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 in the intervention.
Extent of review: Reuse of actual bytes/SHA and historical principles from the retained methods HTML copy for case 1585. No new reading of the full methods text, official application or certification was performed in this exercise.

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 a study solely because its outcomes are not reported.
Extent of review: Reuse of actual bytes/SHA and historical principles from the retained methods HTML copy for case 1585. No new reading of the full methods text, official application or certification was performed in this exercise.

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

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

Referenced principle: Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting.
Extent of review: Reuse of actual bytes/SHA and historical principles from the retained methods HTML copy for case 1585. No new reading of the full methods text, official application or certification was performed in this exercise.

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: Reuse of actual bytes/SHA and historical principles from the retained methods HTML copy for case 1585. No new reading of the full methods text, official application or certification was performed in this exercise.

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

Official methodology · §19.1.2, §19.2.1–19.2.4

Referenced principle: Questions about harms may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence.
Extent of review: Reuse of actual bytes/SHA and historical principles from the retained methods HTML copy for case 1585. No new reading of the full methods text, official application or certification was performed in this exercise.

What the statuses mean

Met: The criterion's identity, attribution within retained materials and interpretive boundaries were verified. This is not confirmation of clinical efficacy/safety or official certification.
Partly verified: Some facts were linked within the currently retained material, but further dimensions of evidence or comparisons remain outstanding.
Unverified: The material read lacks necessary values, criteria or source materials. This does not mean a count or value of 0 for studies, effects or events, or incomplete review in preparing the table.
Conflicting information: The current retained manuscript explicitly states a discrepancy for the same item. The exact scope is preserved without selecting or correcting an original value.
Not applicable: A requirement to impose other extension studies as mandatory for the current narrow score question does not apply. This does not verify other effects or replace an unread status.
Does not apply: A display alias for Not applicable. The original criterion/status is preserved as Not applicable.
Not read: The relevant external or older separate source material was not directly read in this exercise. This is separate from actual reading of the retained summary.
Review incomplete: Actual review of individual criteria/observations for preparation of the table remains outstanding. This is distinct from unverified source information.

Change history

2026-11-05 · Public page/material version 1.0

The public-facing display and data were prepared from the existing 43 items. No new clinical search, change to verification statuses or scoring was performed.

The stored-material review date (2026-10-05) and original evidence cut-off (2026-09-16) 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 and which 12-month score are being compared?

Current findings: The single question is whether adding oral methylcobalamin 1000 µg/day for 12 months lowers the reported painDETECT score compared with placebo on the same background management in adults with type 2 diabetes and confirmed peripheral and autonomic neuropathy who have used metformin for at least 4 years and have B12 <400 pmol/L. The actual subclaims list is empty.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The identity and exclusions of the original question were verified. This does not mean that efficacy or a general analgesic effect has been established.
Reason for missing information: Pain entry criteria, the exact scale version and the adjusted effect estimate remain unverified in separate rows.
Required materials and conditions: The original question and specifications of the population, ingredient, route, dose, comparator, time point and endpoint
Materials to obtain first: The original question and specifications of the population, ingredient, route, dose, comparator, time point and endpoint
Further research: Fix the original question and eligibility criteria, then separately examine only comparisons involving the same population, formulation and score.
Remaining uncertainty: The identity and exclusions of the original question were verified. This does not mean that efficacy or a general analgesic effect has been established.
Conditions for verification: Link the population, methylcobalamin, placebo and 12-month painDETECT comparison in the original /ko/effect and fixed question.
Why this condition is needed: The B12 effects discussed across the page must be distinguished from the selected score comparison.
Application exceptions: The actual subclaims list is empty. Mean pain NRS, all diabetic neuropathy and replacement of analgesics are not added as new subclaims.
Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed — An internally developed, item-specific adaptation for Separate question. No official methodological tool was applied or certification performed.

Related sources S01 S04

N02 · Was methylcobalamin the trial's single active ingredient?

Current findings: The manuscript records methylcobalamin (mecobalamin) as the single added active ingredient. Other cobalamins were not combined with it, and B12 fix is identified as a single-ingredient oral product.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The retained identity of the chemical form and single added ingredient was verified. Product purity and the trial batch were not verified.
Reason for missing information: The historical manufacturing batch and purity are unverified.
Required materials and conditions: The original trial's active ingredient, chemical form and whether it was a combination product
Materials to obtain first: The original trial's active ingredient, chemical form and whether it was a combination product
Further research: Compare the active-ingredient specifications with each original trial's composition to distinguish comparisons of a single added ingredient in the same chemical form.
Remaining uncertainty: The retained identity of the chemical form and single added ingredient was verified. Product purity and the trial batch were not verified.
Conditions for verification: Identify methylcobalamin/mecobalamin as the actual added ingredient and distinguish it from other cobalamins.
Why this condition is needed: Needed to avoid combining effects of different chemical forms or combination products solely on the basis of the name B12.
Application exceptions: Cyanocobalamin, hydroxocobalamin and B-vitamin combinations are not direct evidence for this single-ingredient methylcobalamin comparison.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed — An internally developed, item-specific adaptation for Active ingredient. No official methodological tool was applied or certification performed.

Related sources S01

N03 · Do the supply identity and historical batch of B12 fix match?

Current findings: B12 fix and UNI-PHARMA are identified in the retained manuscript. Manufacturing source, historical trial batch and purity are unverified; the current manufacturer page is not used as evidence that the trial batch was identical.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: Only the product name and supplier were linked. Comparison of the batch, purity and identity with the current product remains outstanding.
Reason for missing information: Historical trial-batch, purity and manufacturing-source documentation is absent.
Required materials and conditions: Trial-product supply records, batch/purity documentation and the current product description
Materials to obtain first: Trial-product supply records, batch/purity documentation and the current product description
Further research: Obtain the trial supply records and contemporaneous batch documentation, and compare them with the current product description while distinguishing their dates.
Remaining uncertainty: Only the product name and supplier were linked. Comparison of the batch, purity and identity with the current product remains outstanding.
Conditions for verification: Record the trial product name and supplier, the current manufacturer description, and historical batch and purity separately.
Why this condition is needed: Needed to avoid treating the current product page as verification of the historical trial batch.
Application exceptions: Linking the UNI-PHARMA name and B12 fix page does not independently confirm the historical batch, purity or efficacy.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed — An internally developed, item-specific adaptation for Trial product. No official methodological tool was applied or certification performed.

Related sources S01 S10

N04 · Has the oral dispersible formulation been reinterpreted as sublingual or injectable?

Current findings: The actual formulation is an oral dispersible tablet. No sublingual holding time is inferred and no injection route is substituted.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The retained identity of the oral formulation and route was linked. Detailed dosing procedures or absorption mechanisms were not verified.
Reason for missing information: A sublingual holding time is not inferred from the manuscript, and historical batch details are unverified.
Required materials and conditions: Trial administration method and oral dispersible formulation specifications
Materials to obtain first: Trial administration method and oral dispersible formulation specifications
Further research: Compare the contemporaneous administration instructions to distinguish the dosing procedure from the actual route.
Remaining uncertainty: The retained identity of the oral formulation and route was linked. Detailed dosing procedures or absorption mechanisms were not verified.
Conditions for verification: Preserve the actual oral dispersible formulation and route without filling in an unreported sublingual holding time.
Why this condition is needed: A formulation that disperses in the mouth cannot be assumed to have the same administration route as sublingual holding or injection.
Application exceptions: Do not add a sublingual holding time, injection route or absorption mechanism absent from the source material.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed — An internally developed, item-specific adaptation for Route of administration. No official methodological tool was applied or certification performed.

Related sources S01

N05 · Has the trial dose been distinguished from total exposure?

Current findings: The trial administered methylcobalamin alone at 1000 µg 1 time daily for 12 months. Total exposure including diet, fortified foods and other additional supplements, and numerical adherence, are unverified.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The nominal trial dose and frequency were linked, but actual total exposure and adherence were not verified.
Reason for missing information: Exposure from diet, fortified foods and additional supplements, and numerical adherence, are unverified.
Required materials and conditions: Trial dose and frequency, dietary/additional supplementation exposure and adherence records
Materials to obtain first: Trial dose and frequency, dietary/additional supplementation exposure and adherence records
Further research: Compare administration, additional supplementation and dietary records by group to assess differences between nominal dose and actual exposure.
Remaining uncertainty: The nominal trial dose and frequency were linked, but actual total exposure and adherence were not verified.
Conditions for verification: Distinguish the trial dose of 1000 µg 1 time daily from total exposure including diet and additional supplementation.
Why this condition is needed: Needed to avoid turning the trial's nominal dose into an individual dosing instruction or actual total intake.
Application exceptions: 1000 µg/day is a trial condition, not an instruction for personal use or a change in diabetes medication.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Nominal dose. No official methodological tool was applied or certification performed.

Related sources S01

N06 · Has the manufacturer's 1000 µg versus 1000 mg labeling been resolved?

Current findings: The retained manuscript records that the current manufacturer page displays both 1000 µg and 1000 mg. This conflict remains unresolved; the trial dose remains 1000 µg/day as specified in S01.
Verification status: Conflicting information
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The manuscript explicitly records inconsistent units on the same product page. Which label, if any, was corrected was not checked in this exercise.
Reason for missing information: A correction resolving the current product-label conflict and comparison with the historical batch are unverified.
Required materials and conditions: Locations of the manufacturer's labels, corrections and contemporaneous trial-dose documentation
Materials to obtain first: Locations of the manufacturer's labels, corrections and contemporaneous trial-dose documentation
Further research: Compare labeling and correction history on the same product page with their original locations to verify the conflict, while maintaining the trial specifications separately.
Remaining uncertainty: The manuscript explicitly records inconsistent units on the same product page. Which label, if any, was corrected was not checked in this exercise.
Conditions for verification: Preserve both printed units on the current product page and handle them separately from the trial dose.
Why this condition is needed: Needed to avoid silently harmonizing conflicting product units or substituting them for the trial dose.
Application exceptions: The conflict on the current product page does not justify changing the original trial's 1000 µg/day to 1000 mg/day.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Conflicting product units. No official methodological tool was applied or certification performed.

Related sources S01 S10

N07 · Has 12-month administration been separated from results over other durations?

Current findings: The selected question and actual trial duration are 12 months. The 4-month nerve-conduction result in S05 is separated as a different duration and endpoint. Observation over 12 months is not reinterpreted as persistence after discontinuation.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The selected time point and duration were linked, with the timing of adjacent results distinguished. The preregistered primary time point remains separately unverified.
Reason for missing information: Registered assessment times and follow-up after discontinuation are unverified.
Required materials and conditions: Trial administration and assessment times, and the duration of each adjacent study
Materials to obtain first: Trial administration and assessment times, and the duration of each adjacent study
Further research: Compare the original time-specific tables and trial schedule to separate administration duration, observation duration and the time point of the selected outcome.
Remaining uncertainty: The selected time point and duration were linked, with the timing of adjacent results distinguished. The preregistered primary time point remains separately unverified.
Conditions for verification: Link the selected score's 12-month time point and administration period without combining the adjacent 4-month result with it.
Why this condition is needed: Studies cannot be counted as direct replications when durations and measurements differ, even if they use the same neuropathy label.
Application exceptions: The 4-month nerve-conduction result in S05 is a different outcome from this 12-month painDETECT comparison.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed — An internally developed, item-specific adaptation for Observation period. No official methodological tool was applied or certification performed.

Related sources S01 S05

N08 · Which adults with diabetic neuropathy were selected?

Current findings: The population comprises adults with type 2 diabetes and confirmed peripheral and autonomic neuropathy who have used metformin for at least 4 years and have B12 <400 pmol/L. This scope is not extended to all diabetic neuropathy.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The core population-selection criteria were preserved, but the pain threshold for entry and minimum duration were not verified.
Reason for missing information: Pain entry criteria, minimum duration and detailed implementation of selection are unverified.
Required materials and conditions: Population diagnoses, duration of metformin use and B12 eligibility criterion
Materials to obtain first: Population diagnoses, duration of metformin use and B12 eligibility criterion
Further research: Compare inclusion/exclusion documentation and baseline characteristics to assess the applicability boundaries of the narrowly selected population.
Remaining uncertainty: The core population-selection criteria were preserved, but the pain threshold for entry and minimum duration were not verified.
Conditions for verification: Link the actual selection criteria: type 2 diabetes, confirmed peripheral and autonomic neuropathy, metformin for ≥4 years and low B12.
Why this condition is needed: Needed to avoid automatically applying the results to all patients with diabetic neuropathy.
Application exceptions: Do not extend the selected population with low B12 and long-term metformin use to diabetes generally or to populations with normal B12.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed — An internally developed, item-specific adaptation for Population selection. No official methodological tool was applied or certification performed.

Related sources S01

N09 · Is B12 <400 pmol/L being interpreted as absolute deficiency in everyone?

Current findings: The manuscript retains B12 <400 pmol/L as the eligibility criterion. This is not reclassified as confirmed absolute deficiency in everyone or used as evidence for supplementation in all patients with normal B12.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The low-B12 selection boundary was linked, but diagnoses of absolute deficiency and effects in a normal-B12 population were not verified.
Reason for missing information: Individual deficiency diagnoses, baseline distribution and direct comparisons in a normal-B12 population are unverified.
Required materials and conditions: Baseline B12 criterion, diagnosis of deficiency and population-specific results
Materials to obtain first: Baseline B12 criterion, diagnosis of deficiency and population-specific results
Further research: Compare diagnostic evidence of deficiency with the eligibility value, and assess extension to a normal-B12 population through a separate comparison.
Remaining uncertainty: The low-B12 selection boundary was linked, but diagnoses of absolute deficiency and effects in a normal-B12 population were not verified.
Conditions for verification: Distinguish the trial's low-B12 criterion from confirmed absolute deficiency and the effects of supplementation in people with normal B12.
Why this condition is needed: A low eligibility value and correction of confirmed deficiency are different questions of applicability.
Application exceptions: Do not classify every participant as having confirmed absolute deficiency solely on the basis of B12 <400 pmol/L.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed — An internally developed, item-specific adaptation for Low-B12 boundary. No official methodological tool was applied or certification performed.

Related sources S01

N10 · Were the pain NRS entry threshold and minimum duration verified?

Current findings: The authors' description of painful neuropathy is preserved, but the entry NRS criterion and minimum pain duration are unverified.
Verification status: Unverified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The exact pain entry criteria cannot be established within the retained material read. This does not mean that participants did not experience pain.
Reason for missing information: Documentation of the pain NRS entry threshold, minimum duration and diagnostic implementation is absent.
Required materials and conditions: Pain diagnosis, entry NRS criterion and minimum duration in the eligibility documentation
Materials to obtain first: Pain diagnosis, entry NRS criterion and minimum duration in the eligibility documentation
Further research: Compare the eligibility documentation and diagnostic procedures to verify actual pain-intensity and duration entry criteria.
Remaining uncertainty: The exact pain entry criteria cannot be established within the retained material read. This does not mean that participants did not experience pain.
Conditions for verification: Distinguish the description of painful neuropathy from the verification status of the exact pain threshold and duration for entry.
Why this condition is needed: The description 'painful' alone does not establish a population with a particular pain intensity or duration of chronic pain.
Application exceptions: Do not reinterpret unverified entry criteria as a population without pain or absence of analgesic efficacy.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Pain entry criteria. No official methodological tool was applied or certification performed.

Related sources S01

N11 · Was selection for stable HbA1c of 6.5–7.5% preserved?

Current findings: The original population is described as adults with stable HbA1c of 6.5–7.5%. Background glycemic management was maintained; the same score effect is not generalized to patients with other glycemic states.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The retained stability criterion and range were linked, but details of actual glycemic-medication changes and management by group are lacking.
Reason for missing information: Detailed records of actual glycemic-medication changes and management exposure by group are unverified.
Required materials and conditions: Baseline glycemic status, stability criteria and glycemic-medication records by group
Materials to obtain first: Baseline glycemic status, stability criteria and glycemic-medication records by group
Further research: Compare baseline glycemic selection criteria and management/medication records by group to assess applicability and concomitant-treatment boundaries.
Remaining uncertainty: The retained stability criterion and range were linked, but details of actual glycemic-medication changes and management by group are lacking.
Conditions for verification: Link the stable HbA1c range with the population receiving common glycemic management.
Why this condition is needed: Needed to avoid applying the result of adjunctive treatment on stable glycemic management to all glycemic states.
Application exceptions: A nonsignificant result for HbA1c change is not a direct substitute for this stable-range selection criterion or the painDETECT result.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Glycemic-status selection. No official methodological tool was applied or certification performed.

Related sources S01

N12 · Was the full composition of the similar-looking placebo verified?

Current findings: The comparator conditions are a similar-looking placebo and stable common glycemic management. Full placebo excipients and the historical batch are unverified.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The framework of the placebo comparison was linked, but full composition and batch identity were not verified.
Reason for missing information: Documentation of full placebo excipients, batch and implementation of blinding is unverified.
Required materials and conditions: Placebo appearance, composition and batch, and common management in each group
Materials to obtain first: Placebo appearance, composition and batch, and common management in each group
Further research: Compare contemporaneous placebo specifications and manufacturing records to assess comparator composition and implementation of blinding.
Remaining uncertainty: The framework of the placebo comparison was linked, but full composition and batch identity were not verified.
Conditions for verification: Record the similar-looking placebo comparison separately from the unverified full excipient composition.
Why this condition is needed: Needed to avoid confusing similar appearance with complete placebo identity or biological inactivity.
Application exceptions: Do not conclude that the placebo was an active treatment or that blinding was broken because its full composition is unverified.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Placebo specifications. No official methodological tool was applied or certification performed.

Related sources S01

N13 · Were common glycemic management and adjustment variables distinguished?

Current findings: Background glycemic management was maintained, and the formal comparison of change adjusted for HbA1c and glycemic medications. A common management policy and actual changes by group are different information; detailed change records are unverified.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The policy and adjustment variables were linked, but detailed comparison of actual concomitant exposure by group and the handling of changes remains outstanding.
Reason for missing information: Glycemic-medication changes by group, details of the adjustment model and specification of the effect of interest are unverified.
Required materials and conditions: Glycemic medications and management changes by group, and ANCOVA adjustment specifications
Materials to obtain first: Glycemic medications and management changes by group, and ANCOVA adjustment specifications
Further research: Compare concomitant-treatment changes by group and analysis specifications to assess the selected intervention's contribution and the effect of interest.
Remaining uncertainty: The policy and adjustment variables were linked, but detailed comparison of actual concomitant exposure by group and the handling of changes remains outstanding.
Conditions for verification: Record the common management policy, actual treatment changes by group, and adjustment for HbA1c/glycemic medications separately.
Why this condition is needed: Needed to avoid using a common policy as proof that all actual treatments were identical.
Application exceptions: Do not indicate that all differences in concomitant treatment, confounding and adherence were resolved merely because adjustment variables were used.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Common treatment. No official methodological tool was applied or certification performed.

Related sources S01

N14 · Is the policy permitting paracetamol the same as actual use?

Current findings: The retained policy restricted other analgesics and permitted occasional paracetamol for only 2–3 days. The actual amount of rescue medication used is unverified.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The analgesic policy was verified, but actual amounts used by group and handling in the analysis were not verified.
Reason for missing information: Data on the amount and frequency of paracetamol use by group and handling in the analysis are unverified.
Required materials and conditions: Rescue-analgesic policy, amount used and changes by group, and handling in the analysis
Materials to obtain first: Rescue-analgesic policy, amount used and changes by group, and handling in the analysis
Further research: Compare rescue-medication use records by group to assess the relationship between the score comparison and concurrent treatment.
Remaining uncertainty: The analgesic policy was verified, but actual amounts used by group and handling in the analysis were not verified.
Conditions for verification: Distinguish restrictions on other analgesics and occasional paracetamol permitted for 2–3 days from the actual amounts used by group.
Why this condition is needed: A permission rule alone cannot establish that actual analgesic exposure was identical between groups.
Application exceptions: Do not interpret the policy restricting analgesics as an effect replacing analgesics, or fill in actual use as 0.
Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Rescue analgesics. No official methodological tool was applied or certification performed.

Related sources S01

N15 · Were numerical adherence and additional B12 exposure verified?

Current findings: Diet, fortified foods, total additional-supplement exposure and numerical adherence are unverified. The report that everyone completed 12 months does not guarantee actual intake or full adherence.
Verification status: Unverified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The material read contains no numerical data on actual exposure or adherence. Unverified information is not treated as proof of nonadherence or absence of additional supplementation.
Reason for missing information: Numerical adherence, diet and additional-supplement exposure data by group are lacking.
Required materials and conditions: Dosing records and numerical adherence by group, and records of diet, fortified foods and additional supplementation
Materials to obtain first: Dosing records and numerical adherence by group, and records of diet, fortified foods and additional supplementation
Further research: Compare dosing, diet and additional-exposure records, and assess their handling in relation to the effect of interest.
Remaining uncertainty: The material read contains no numerical data on actual exposure or adherence. Unverified information is not treated as proof of nonadherence or absence of additional supplementation.
Conditions for verification: Distinguish nominal administration from actual dosing, diet, fortified foods and other supplementation exposure.
Why this condition is needed: Needed because reported completion by everyone differs from actual adherence.
Application exceptions: Do not substitute 90 fully adherent participants or identical total intake for the 90 reported completers.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Adherence and diet. No official methodological tool was applied or certification performed.

Related sources S01

N16 · Is the painDETECT total score a mean pain-intensity NRS?

Current findings: The original paper-form total score in S04 has a range of −1–38. It sums sensory qualities, pain course and radiation; the items recording pain intensity are not included in the total score. The selected painDETECT score is not a mean pain NRS/VAS.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The retained scale components and endpoint boundaries were verified. The exact language/version used in the trial and an applicable criterion for clinically important change remain separately unverified.
Reason for missing information: The exact questionnaire language/version used in the trial and clinical importance are unverified.
Required materials and conditions: Original scale definition, total-score components, range and direction
Materials to obtain first: Original scale definition, total-score components, range and direction
Further research: Compare the original scale definition with the items actually used in the trial to assess how the total score relates to the intensity items.
Remaining uncertainty: The retained scale components and endpoint boundaries were verified. The exact language/version used in the trial and an applicable criterion for clinically important change remain separately unverified.
Conditions for verification: Distinguish the screening composite of sensory qualities, pain course and radiation from items recording pain intensity.
Why this condition is needed: Needed to avoid elevating a screening total score to a reduction in mean pain NRS/VAS.
Application exceptions: Preserve the scale's original screening purpose while retaining the comparison of the patient-reported score itself selected for this page.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4; internally defined boundaries for extending the claim — An internally developed, item-specific adaptation for Scale definition. No official methodological tool was applied or certification performed.

Related sources S01 S04

N17 · Were the trial questionnaire's language, version and recall period verified?

Current findings: The exact questionnaire language, version and recall period are unverified. A historical record of reading the original painDETECT definition does not substitute for the trial's actual questionnaire implementation.
Verification status: Unverified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The trial's measurement implementation cannot be established from the stored materials read. This is not a judgment that the scale is invalid.
Reason for missing information: The questionnaire language, version, recall period and scoring procedure are unverified.
Required materials and conditions: Trial questionnaire, language/translation, version, recall period and scoring procedure
Materials to obtain first: Trial questionnaire, language/translation, version, recall period and scoring procedure
Further research: Compare the contemporaneous questionnaire and scoring procedure with the original scale definition to assess how the actual measurement corresponds to it.
Remaining uncertainty: The trial's measurement implementation cannot be established from the stored materials read. This is not a judgment that the scale is invalid.
Conditions for verification: Distinguish the original scale description from the verification status of the language, version and recall period actually used in the trial.
Why this condition is needed: The original scale definition does not verify all aspects of how measurement was actually implemented in the trial.
Application exceptions: Do not infer the trial questionnaire version or recall period from the original scale's total-score range.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Questionnaire implementation. No official methodological tool was applied or certification performed.

Related sources S01 S04

N18 · Was the page's primary endpoint at 12 months distinguished from a registered primary (1st) endpoint?

Current findings: The selected outcome is the between-group comparison of change in reported painDETECT score at 12 months. It is the page's primary endpoint, but whether it was prespecified as primary (1st) in the original registration is unverified.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The reported time point and the page's selection were verified, but the preregistered hierarchy could not be compared.
Reason for missing information: The registration's initial posting, amendment history and pain-endpoint hierarchy are unverified.
Required materials and conditions: Outcome time points, original registration hierarchy, initial posting and amendment history
Materials to obtain first: Outcome time points, original registration hierarchy, initial posting and amendment history
Further research: Compare the initial registration and timing of outcome reporting to assess how selection occurred and why changes were made.
Remaining uncertainty: The reported time point and the page's selection were verified, but the preregistered hierarchy could not be compared.
Conditions for verification: Record the reported score at 12 months selected for this page separately from the verification status of the preregistered primary endpoint.
Why this condition is needed: Needed to avoid automatically turning the page's primary endpoint into a preregistered primary (1st) outcome.
Application exceptions: Do not reinterpret an unverified registration hierarchy as confirmed absence of registration or confirmed selective reporting.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application — An internally developed, item-specific adaptation for Selected time point. No official methodological tool was applied or certification performed.

Related sources S01 S03

N19 · Was the RCT designation distinguished from implementation of allocation concealment?

Current findings: The original trial is retained as randomized, placebo-controlled and double-blind. How allocation concealment was implemented was not reported and was included in the original B2 rationale separately from the small trial size.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The design designation and limitations in the original assessment were linked. Detailed implementation was not compared, and no new bias-assessment tool was applied.
Reason for missing information: Detailed source documentation of allocation concealment and implementation of blinding is unverified.
Required materials and conditions: Original trial design, allocation/concealment, implementation of blinding and baseline data
Materials to obtain first: Original trial design, allocation/concealment, implementation of blinding and baseline data
Further research: Compare allocation procedures, placebo specifications and assessment-blinding documentation to assess potential bias in the selected score.
Remaining uncertainty: The design designation and limitations in the original assessment were linked. Detailed implementation was not compared, and no new bias-assessment tool was applied.
Conditions for verification: Link the randomized, placebo-controlled, double-blind design and the unreported implementation of allocation concealment to each outcome.
Why this condition is needed: Needed because a design designation alone cannot establish absence of allocation or measurement bias.
Application exceptions: Do not present unreported implementation of allocation concealment as actual concealment failure or an established magnitude of bias.
Referenced methods: M08 §8.1–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Allocation and blinding. No official methodological tool was applied or certification performed.

Related sources S01

N20 · Are allocation of 90 participants, 44/46 by group, and completion being read as analysis denominators?

Current findings: Of 90 participants, 44 were allocated to methylcobalamin and 46 to placebo; all reportedly completed 12 months. Separate endpoint-specific analysis denominators were not reported.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The retained allocation and completion values were linked, but the actual painDETECT analysis denominators were not verified.
Reason for missing information: Endpoint-specific measurement and analysis denominators and documentation of exclusions/missing-data handling are unverified.
Required materials and conditions: Flow diagram and denominators for allocation, completion, measurement and analysis by group
Materials to obtain first: Flow diagram and denominators for allocation, completion, measurement and analysis by group
Further research: Compare the flow diagram and endpoint-specific analysis tables to link participant counts for allocation → completion → measurement → analysis.
Remaining uncertainty: The retained allocation and completion values were linked, but the actual painDETECT analysis denominators were not verified.
Conditions for verification: Preserve allocation and reported completion of 44/46 separately from endpoint-specific analysis denominators.
Why this condition is needed: Needed to avoid automatically using a statement that everyone completed the trial as the analysis denominator for each outcome.
Application exceptions: Do not treat the 90 reported completers as a verified painDETECT analysis n=90 or group-specific n=44/46.
Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Allocation and completion. No official methodological tool was applied or certification performed.

Related sources S01

N21 · Were the painDETECT analysis population and missing-data handling verified?

Current findings: Endpoint-specific analysis denominators were not reported. Reported completion of 44/46 does not establish ITT, PP or 0 missing data; the original assessment also did not provide a standardized effect for endpoint values because the denominators were unverified.
Verification status: Unverified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The analysis population and missing-data handling for the selected score cannot be established from the material read. These are distinguished from the report that everyone completed the trial.
Reason for missing information: Exact analysis n, ITT/PP, reasons for missing data/exclusions and handling specifications are unverified.
Required materials and conditions: PainDETECT analysis denominators by group, analysis population, reasons for missing data/exclusions and their handling
Materials to obtain first: PainDETECT analysis denominators by group, analysis population, reasons for missing data/exclusions and their handling
Further research: Compare outcome-specific analysis specifications and missing-data/exclusion records to assess the effect of interest and the actual analysis population.
Remaining uncertainty: The analysis population and missing-data handling for the selected score cannot be established from the material read. These are distinguished from the report that everyone completed the trial.
Conditions for verification: Distinguish endpoint-specific analysis populations, ITT/PP and missing-data handling from reported completion.
Why this condition is needed: Needed to avoid filling in absent analysis populations and denominators as ITT or all completers.
Application exceptions: Do not arbitrarily label an unreported analysis population as ITT/PP or fill in dropouts and missing data as 0.
Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Analysis population and missing data. No official methodological tool was applied or certification performed.

Related sources S01

N22 · Are the original scores, existing change contrast and endpoint difference being read as the same estimate?

Current findings: Table 4 reports scores of 18.4→17.1 in the methylcobalamin group and 19.3→20.9 in the placebo group. The manuscript's simple change contrast of −2.9 points and endpoint difference of −3.8 points are existing unadjusted descriptive values; neither is an unreported adjusted estimate. No new calculation was performed in this exercise.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The definitions, directions and attribution of the original scores and existing descriptive differences were preserved. The formal adjusted effect estimate and CI were not verified.
Reason for missing information: The formal adjusted coefficient, SE, CI and endpoint-specific analysis denominators are unverified.
Required materials and conditions: Scores and time points in the original results table, definitions of existing descriptive differences and adjusted results
Materials to obtain first: Scores and time points in the original results table, definitions of existing descriptive differences and adjusted results
Further research: Compare the original table and analysis definitions to assess the correspondence among original scores, descriptive differences and the formal adjusted effect.
Remaining uncertainty: The definitions, directions and attribution of the original scores and existing descriptive differences were preserved. The formal adjusted effect estimate and CI were not verified.
Conditions for verification: Preserve 18.4→17.1 versus 19.3→20.9 and the manuscript's descriptive values of −2.9/−3.8 separately.
Why this condition is needed: Needed to avoid confusing within-group change, between-group difference in change, endpoint difference and an adjusted coefficient.
Application exceptions: Do not present the existing −2.9 and −3.8 as new calculations or unreported adjusted estimates.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Original scores and descriptive differences. No official methodological tool was applied or certification performed.

Related sources S01

N23 · Has P<0.001 been turned into an adjusted coefficient, SE or CI?

Current findings: The formal comparison of change adjusted for HbA1c and glycemic medications reports P<0.001. The original assessment records adjusted ANCOVA, but the adjusted coefficient, SE and CI were not reported. formal_adjusted_CI is null, not 0. It is not replaced by an unadjusted descriptive difference.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The formal analysis type, adjustment variables and P reported as an inequality were linked. The formal effect magnitude and interval were not verified.
Reason for missing information: The adjusted coefficient, SE, CI, exact analysis denominators and model output are unverified.
Required materials and conditions: ANCOVA specifications, adjusted coefficient, SE, CI, denominators and results table
Materials to obtain first: ANCOVA specifications, adjusted coefficient, SE, CI, denominators and results table
Further research: Compare formal model output and the results table to verify the formal effect of interest, interval and denominators.
Remaining uncertainty: The formal analysis type, adjustment variables and P reported as an inequality were linked. The formal effect magnitude and interval were not verified.
Conditions for verification: Link the formal ANCOVA comparison of change, adjustment variables and reported P separately from the unreported coefficient/SE/CI.
Why this condition is needed: Needed to avoid establishing effect magnitude or precision from statistical significance alone.
Application exceptions: P<0.001 is not an exact P value; no adjusted CI or standardized effect is newly back-calculated.
Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application — An internally developed, item-specific adaptation for Adjusted effect and interval. No official methodological tool was applied or certification performed.

Related sources S01

N24 · Have the baseline SD values of 9.2 and 9.7 been silently harmonized?

Current findings: The manuscript preserves the baseline SD conflict of 9.2 versus 9.7 in the original table, without harmonizing the values as though resolved. The exact table cell, group attribution or correction status of each value is not newly established from the current stored summary alone.
Verification status: Conflicting information
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The manuscript explicitly records inconsistent values for the same baseline SD. The conflict remains unresolved because the original PDF/table was not reopened in this exercise.
Reason for missing information: Exact table cells, group/time-point attribution and correction history are unverified.
Required materials and conditions: Locations of baseline SD in the original Table 4 and text, corrections, and group/time-point specifications
Materials to obtain first: Locations of baseline SD in the original Table 4 and text, corrections, and group/time-point specifications
Further research: Compare the original table, relevant text and correction history for the same group/time point to verify the location and attribution of the SD conflict.
Remaining uncertainty: The manuscript explicitly records inconsistent values for the same baseline SD. The conflict remains unresolved because the original PDF/table was not reopened in this exercise.
Conditions for verification: Retain the conflict between the two baseline SD values reported in the retained manuscript and their unresolved attribution.
Why this condition is needed: Needed to avoid arbitrarily selecting or correcting conflicting variability values, or using them as established inputs for a CI calculation.
Application exceptions: Preserve only the recorded conflict of 9.2 versus 9.7 without filling in table cells or group attribution absent from the current stored summary.
Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Conflicting baseline SD. No official methodological tool was applied or certification performed.

Related sources S01

N25 · Is there an applicable MCID for painDETECT change in this population?

Current findings: An applicable criterion for clinical importance is unverified. The manuscript did not assign EX solely because an MCID was absent; it separately records the unverified adjusted estimate, SE, CI and analysis denominators.
Verification status: Unverified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The clinical importance of the score change in the selected population cannot be established within the current scope.
Reason for missing information: An applicable MCID, scale implementation and formal effect interval are unverified.
Required materials and conditions: Evidence for an MCID applicable to this population, scale version and change estimate
Materials to obtain first: Evidence for an MCID applicable to this population, scale version and change estimate
Further research: Compare evidence on important change in the same population and scale version with the score definition, and interpret it alongside the reported interval.
Remaining uncertainty: The clinical importance of the score change in the selected population cannot be established within the current scope.
Conditions for verification: Distinguish a criterion for an important difference applicable to the selected score, population and time point from a diagnostic screening threshold.
Why this condition is needed: Needed to avoid elevating a statistically significant score difference to a clinically important mean analgesic effect.
Application exceptions: Do not turn a screening total-score threshold into an MCID or substitute thresholds from another disease or language. Do not reassess the original EX solely because an MCID is absent.
Referenced methods: M15 §15.3.1–15.3.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Clinical importance. No official methodological tool was applied or certification performed.

Related sources S01 S04

N26 · Was the identity of NCT04706377 distinguished from reading its content?

Current findings: NCT04706377 is the registration number linked to the original trial. Historical access was registration_shell_only; the record states that the initial posting date, amendment history, primary pain-endpoint hierarchy and prespecified analysis plan could not be verified. The registration was not queried in this exercise either.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The registration identity is preserved, but comparison of the registration content and prespecified hierarchy remains incomplete.
Reason for missing information: The initial posting, amendment history, readable endpoint hierarchy and protocol/SAP are unverified.
Required materials and conditions: Original registration record, initial posting, amendment history and outcome hierarchy
Materials to obtain first: Original registration record, initial posting, amendment history and outcome hierarchy
Further research: Compare the initial registration and amendment history with outcome reporting to assess temporal order, the selected endpoint and reasons for changes.
Remaining uncertainty: The registration identity is preserved, but comparison of the registration content and prespecified hierarchy remains incomplete.
Conditions for verification: Distinguish linking a registration number from obtaining the initial posting, amendment history and readable endpoint hierarchy.
Why this condition is needed: Needed to avoid turning the existence of a registration number into verification of a prespecified primary (1st) endpoint or registration timing.
Application exceptions: Do not present historical access classified as registration_shell_only as reading the full registration or as confirmation that the trial was unregistered.
Referenced methods: M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application — An internally developed, item-specific adaptation for Registration history. No official methodological tool was applied or certification performed.

Related sources S01 S03

N27 · Were the protocol and SAP compared with the selection of actual results?

Current findings: The protocol, SAP and registered endpoint hierarchy are unverified. The original assessment describes multiple endpoints, prespecified hierarchy and inconsistent diagnostic criteria as separate risks; primary_failed_secondary_positive and coprimary_split in axes are null.
Verification status: Unverified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: Without a direct comparison of plans and reporting, prespecification, the circumstances of changes and handling of multiple endpoints are not established.
Reason for missing information: The protocol, SAP, handling of multiple endpoints and documentation of reasons for changes are unverified.
Required materials and conditions: Protocol, SAP, prespecified endpoints/analyses/time points, handling of multiple endpoints and reporting
Materials to obtain first: Protocol, SAP, prespecified endpoints/analyses/time points, handling of multiple endpoints and reporting
Further research: Compare the registration, protocol and SAP with all reported endpoints, analyses and time points to assess changes to the plan and reasons for selection.
Remaining uncertainty: Without a direct comparison of plans and reporting, prespecification, the circumstances of changes and handling of multiple endpoints are not established.
Conditions for verification: Distinguish unavailable plans and unverified multiple-endpoint handling and prespecified hierarchy from confirmed selective reporting.
Why this condition is needed: Needed to expose the lack of materials for assessing whether only favorable scores were selected.
Application exceptions: Do not treat unavailable materials as confirmation of selective reporting or arbitrarily fill in primary_failed_secondary_positive as true/false.
Referenced methods: M08 Table 8.2.a, M04 §4.6.3; internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Plans and multiple endpoints. No official methodological tool was applied or certification performed.

Related sources S01 S03

N28 · Were nonsignificant results for MNSIE and HbA1c preserved?

Current findings: The manuscript also preserves the between-group MNSIE P=0.607 and HbA1c P=0.876. Nonsignificance for these two different endpoints is not reinterpreted as direct refutation of painDETECT, equivalence or an effect of 0.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The manuscript's other endpoints, results without a significant difference and attribution boundaries were preserved. Their full analyses and intervals were not verified.
Reason for missing information: Detailed denominators, analyses and intervals for the two endpoints are unverified in the current summary.
Required materials and conditions: All reported endpoints, denominators, time points and analyses, including favorable results and results without a significant difference
Materials to obtain first: All reported endpoints, denominators, time points and analyses, including favorable results and results without a significant difference
Further research: Compare each endpoint, denominator and analysis in the complete results table to assess how favorable results and those without a significant difference relate to the selected score.
Remaining uncertainty: The manuscript's other endpoints, results without a significant difference and attribution boundaries were preserved. Their full analyses and intervals were not verified.
Conditions for verification: Attribute P=0.607 and P=0.876 to their other endpoints separately from the selected painDETECT outcome.
Why this condition is needed: Other endpoints without a significant difference must be preserved alongside favorable scores, rather than retaining only favorable scores.
Application exceptions: Do not reinterpret nonsignificance as an effect of 0, equivalence or direct refutation of the painDETECT result.
Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed — An internally developed, item-specific adaptation for Results without a significant difference. No official methodological tool was applied or certification performed.

Related sources S01

N29 · Are S01, S02 and S03 being counted as three replications?

Current findings: S01's DOI 10.3390/nu13020395, PMID 33513879 and PMCID PMC7912007 correspond to the S02 bibliographic record, and NCT04706377 is linked to S03. The original trial, index and registration records in F01 are not counted as 3 independent replications.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The retained identifiers and registration linkage for the same original trial were verified. The full registration and all related reports were not exhaustively checked in this exercise.
Reason for missing information: Exhaustive comparison of all related reports and study families, and the total number of unique participants, remain undetermined.
Required materials and conditions: DOI, PMID, PMCID, registration number and report-family linkage
Materials to obtain first: DOI, PMID, PMCID, registration number and report-family linkage
Further research: Compare identifiers, trial numbers and original-report identities to link reports belonging to the same trial family.
Remaining uncertainty: The retained identifiers and registration linkage for the same original trial were verified. The full registration and all related reports were not exhaustively checked in this exercise.
Conditions for verification: Link the original trial, NLM bibliographic record and registration number within F01, distinguishing them from independent replication.
Why this condition is needed: Needed to avoid converting the number of article, bibliographic and registration reports into a count of unique trials.
Application exceptions: Do not delete bibliographic/registration records because they lack separate results, or add linked records as new independent trials.
Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Same-trial family. No official methodological tool was applied or certification performed.

Related sources S01 S02 S03

N30 · Are improvement and the absence of a significant nerve-conduction difference in S05 being read as replication of the same question?

Current findings: The 1992 abstract for F02 reported improvement in somatic and autonomic symptoms, but stated that nerve-conduction changes at 4 months were not significant. Exact between-group painDETECT values, the same population, dose and relevant denominators are unverified; it was not counted as a direct replication.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: Favorable symptom results, nerve-conduction results without a significant difference and the reasons for exclusion were preserved together. Replication within the exact boundaries was not verified.
Reason for missing information: The same population, dose, scale, between-group scores, denominators and original full text are unverified.
Required materials and conditions: S05 original abstract, population/dose/scale, denominators, duration and results
Materials to obtain first: S05 original abstract, population/dose/scale, denominators, duration and results
Further research: Compare population, dose, measurements and denominators in the original abstract and full text to distinguish direct replication from adjacent symptom results.
Remaining uncertainty: Favorable symptom results, nerve-conduction results without a significant difference and the reasons for exclusion were preserved together. Replication within the exact boundaries was not verified.
Conditions for verification: Record F02's symptom improvement and nonsignificant nerve-conduction result at 4 months alongside the unverified selected score, population and dose.
Why this condition is needed: Needed to avoid creating an exact painDETECT replication from favorable related symptom results alone.
Application exceptions: Do not substitute nonsignificant nerve-conduction results at 4 months for no effect on the selected 12-month painDETECT outcome.
Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Adjacent 1992 trial. No official methodological tool was applied or certification performed.

Related sources S05

N31 · Is a comparison of 1000 versus 2000 µg a placebo-controlled replication?

Current findings: F03's 2026 title compares oral B12 at 1000 µg versus 2000 µg. It has no control without supplementation, and the record states that direct numerical pain results could not be verified from the accessed metadata. It was not counted as a direct replication of the placebo comparison.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The active-dose comparison's identity and reason for exclusion as a direct replication were preserved. Exact pain outcomes, population and chemical form were not verified.
Reason for missing information: The original full text, numerical pain results, denominators and exact correspondence of chemical form/population are unverified.
Required materials and conditions: S06 population, chemical form, active doses, endpoints, denominators and full results
Materials to obtain first: S06 population, chemical form, active doses, endpoints, denominators and full results
Further research: Compare the original trial's population, chemical form, doses, comparator and endpoints, and assess dose comparison as a separate question.
Remaining uncertainty: The active-dose comparison's identity and reason for exclusion as a direct replication were preserved. Exact pain outcomes, population and chemical form were not verified.
Conditions for verification: Distinguish F03's comparison of two active doses from a placebo comparison without supplementation, without filling in unverified pain values.
Why this condition is needed: A comparison of two active doses differs from the efficacy question of added B12 versus no supplementation.
Application exceptions: Do not automatically establish that oral B12 in the title means the exact methylcobalamin form, the same painDETECT endpoint or the same population.
Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed — An internally developed, item-specific adaptation for 2026 active-dose comparison. No official methodological tool was applied or certification performed.

Related sources S06

N32 · Are S11 and S12 being counted as new independent replications?

Current findings: S11 is retained as a discovery excerpt with failed full-text access, and S12 as discovery metadata for a review/meta-analysis of mixed B-vitamin types, routes and formulations. Neither is counted toward direct effects; no included-study table or exact replication count is newly created here.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: Discovery identities and historical access limitations were linked. Comparison of included studies and families addressing the same question remains incomplete.
Reason for missing information: Review full texts, included-study tables, original-report families and results within the same boundaries are unverified.
Required materials and conditions: Reviews' included-study tables, original-trial identities, chemical forms/routes/endpoints and duplicate-report linkage
Materials to obtain first: Reviews' included-study tables, original-trial identities, chemical forms/routes/endpoints and duplicate-report linkage
Further research: Link the trials included in reviews to original reports, then individually compare family overlap, differences in conditions and unverified results.
Remaining uncertainty: Discovery identities and historical access limitations were linked. Comparison of included studies and families addressing the same question remains incomplete.
Conditions for verification: Distinguish review identities used for discovery from comparison of the actual inclusion and results of independent original trials.
Why this condition is needed: Needed to avoid adding discovery citations to the number of independent trials addressing the same question.
Application exceptions: Do not use reviews of mixed B-vitamin types, routes and formulations as direct results for a single-ingredient methylcobalamin painDETECT comparison.
Referenced methods: M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Reviews and discovery leads. No official methodological tool was applied or certification performed.

Related sources S11 S12

N33 · Were product supply and no external funding reinterpreted as independent funding?

Current findings: The original trial retains declarations of no external research funding, in-kind company supply of product and placebo, no company involvement and no conflicts of interest. The original assessment's I1 is not changed to public independent funding I2 or manufacturer-only I0.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The reported declarations were linked, but no verification by an independent institution or new exhaustive review of interests was performed.
Reason for missing information: Detailed contracts, author/institutional relationships and independent verification are unverified.
Required materials and conditions: Research funding, product/placebo supply, company role, COI and institutional/author declarations
Materials to obtain first: Research funding, product/placebo supply, company role, COI and institutional/author declarations
Further research: Compare funding, supply, company roles and author declarations report by report, recording the scope of verification and omissions.
Remaining uncertainty: The reported declarations were linked, but no verification by an independent institution or new exhaustive review of interests was performed.
Conditions for verification: Preserve separately the scope of declarations of no external research funding, company product/placebo supply, no involvement and no COI.
Why this condition is needed: Needed to avoid confusing in-kind product supply with funding and independent replication.
Application exceptions: Do not use company supply as an automatic reason for exclusion or infer public independent funding I2 or manufacturer-only I0 from no external funding.
Referenced methods: Chamgap's own criteria for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items — An internally developed, item-specific adaptation for Funding and independence. No official methodological tool was applied or certification performed.

Related sources S01

N34 · Is nonreporting of suspected B12-related AEs being read as 0 AEs of any kind?

Current findings: The manuscript retains the report that no suspected B12-related adverse reactions were reported in the limited trial. Group-specific denominators for all AEs/SAEs, collection methods, discontinuations and safety over the long term or in special populations are unverified. This is not reinterpreted as 0 events of any kind or as harm incidence.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The narrow scope of the original harms report was preserved. The complete event and discontinuation records, denominators and collection system were not verified.
Reason for missing information: All AEs, SAEs, discontinuations, collection methods, events/people and denominators by group, and long-term/special-population data, are unverified.
Required materials and conditions: All AEs, SAEs, relatedness, discontinuations, collection methods, events/people and denominators/duration by group
Materials to obtain first: All AEs, SAEs, relatedness, discontinuations, collection methods, events/people and denominators/duration by group
Further research: Compare original safety tables and collection, relatedness and discontinuation records by group to distinguish people, events, duration and unreported information.
Remaining uncertainty: The narrow scope of the original harms report was preserved. The complete event and discontinuation records, denominators and collection system were not verified.
Conditions for verification: Distinguish the report that no suspected B12-related adverse reactions were observed from all AEs/SAEs, discontinuations, denominators and the scope of collection.
Why this condition is needed: Needed to avoid turning limited reporting of relatedness into absence of all events or verified safety.
Application exceptions: Do not substitute 0 AEs, SAEs or discontinuations for the report that everyone completed the trial, or newly calculate event rates.
Referenced methods: M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed differentiation is internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application — An internally developed, item-specific adaptation for Trial reporting of harms. No official methodological tool was applied or certification performed.

Related sources S01 S07 S08 S09

N35 · Is the safety context of metformin and low B12 an analgesic effect?

Current findings: S07 is an MHRA safety document concerning the association between metformin and low B12 and risk monitoring. The retained manuscript uses it as population and safety context, not as evidence for a methylcobalamin pain effect or individual medication changes.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The retained role of the official document and the boundaries excluding efficacy claims and personal instructions were verified. The official source text was not read in this exercise.
Reason for missing information: Changes to the current official document and applicability to individuals were not checked in this exercise.
Required materials and conditions: Population, scope of recommendations and original location in official document S07
Materials to obtain first: Population, scope of recommendations and original location in official document S07
Further research: Compare the official document's exposure, population and recommendations with the original trial question to distinguish safety context from efficacy claims.
Remaining uncertainty: The retained role of the official document and the boundaries excluding efficacy claims and personal instructions were verified. The official source text was not read in this exercise.
Conditions for verification: Distinguish the MHRA risk-monitoring context from efficacy of the selected methylcobalamin intervention and individual medication changes.
Why this condition is needed: Needed to avoid reversing an association between medication and B12 status into an analgesic effect of supplementation.
Application exceptions: Do not use the official monitoring document to justify a methylcobalamin painDETECT effect or an individual change in metformin.
Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied — An internally developed, item-specific adaptation for Official metformin document. No official methodological tool was applied or certification performed.

Related sources S07

N36 · Has the cobalt warning been repurposed as a methylcobalamin event rate?

Current findings: The MHRA cobalt-sensitivity notice in S08 explicitly names hydroxocobalamin and cyanocobalamin. This warning was not repurposed as harm incidence in the methylcobalamin trial; warnings for other products and individual safety are distinguished.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The chemical forms explicitly named in the retained notice and limits on transferring it were verified. This does not mean that methylcobalamin has no allergy risk.
Reason for missing information: Direct chemical-form-specific methylcobalamin events, denominators and individual applicability are unverified.
Required materials and conditions: Specified products, chemical forms and scope of sensitivity reactions in official notice S08
Materials to obtain first: Specified products, chemical forms and scope of sensitivity reactions in official notice S08
Further research: Compare the notice's specified chemical forms and reactions with the trial formulation and population to assess the scope of the warning's applicability.
Remaining uncertainty: The chemical forms explicitly named in the retained notice and limits on transferring it were verified. This does not mean that methylcobalamin has no allergy risk.
Conditions for verification: Preserve the chemical-form and event scope of the warning explicitly naming hydroxocobalamin and cyanocobalamin.
Why this condition is needed: Needed to avoid transferring warnings for other cobalamins to harm incidence in this trial or individual safety.
Application exceptions: Do not turn a cobalt-sensitivity warning into confirmation that methylcobalamin is risk-free, or that causality or frequency of harm is established.
Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied — An internally developed, item-specific adaptation for Warnings for other chemical forms. No official methodological tool was applied or certification performed.

Related sources S08

N37 · Does the ODS statement that no UL is established mean unlimited safety?

Current findings: S09 is a record reusing a citation/safety excerpt from prior record 110, with original verified_date=2026-07-07. NIH's statement that no UL is established is not a guarantee of unlimited safety. The ODS original and prior record 110 file were not read in this exercise; that record was checked only in the current case 3111 summary.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The inherited description and historical source were linked. The original ODS text, original bytes of prior record 110 and long-term/special-population safety were not compared in this exercise.
Reason for missing information: The current ODS original, original bytes of the prior record 110 excerpt and long-term/special-population harms data are unverified.
Required materials and conditions: Original S09 ODS text, actual content/review history of the excerpt from prior record 110, and long-term/special-population safety data
Materials to obtain first: Original S09 ODS text, actual content/review history of the excerpt from prior record 110, and long-term/special-population safety data
Further research: Separately compare the original location of the ODS description, the prior excerpt and long-term/special-population harms data to assess how absence of an upper limit can be interpreted.
Remaining uncertainty: The inherited description and historical source were linked. The original ODS text, original bytes of prior record 110 and long-term/special-population safety were not compared in this exercise.
Conditions for verification: Distinguish the inherited UL description and source-material review date from prior record 110 from actual reading in the current exercise.
Why this condition is needed: Needed because absence of a UL differs from a guarantee of safety at high doses, over the long term or in all populations.
Application exceptions: Do not present the review date 2026-07-07 from prior record 110 as the actual access date of S09 or the date of reading ODS in this exercise.
Referenced methods: M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied — An internally developed, item-specific adaptation for UL and reused source. No official methodological tool was applied or certification performed.

Related sources S09

N38 · Does this also answer optimal dose, persistence after stopping and effects in people with normal B12?

Current findings: The selected conditions are 1000 µg/day for 12 months in people with long-term metformin use and low B12. Optimal dose, maintenance after discontinuation and effects in a normal-B12 population are unverified. S06's comparison of different active doses is not automatically used to verify these extensions.
Verification status: Unverified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The direct evidence required for extensions beyond the selected scope was not verified. No new mandatory conditions were added to the original score comparison.
Reason for missing information: Direct estimates for optimal dose, post-discontinuation follow-up and normal-B12 populations/subgroups are unverified.
Required materials and conditions: Direct dose comparisons, follow-up after discontinuation and prespecified interaction results for normal-B12 populations/subgroups
Materials to obtain first: Direct dose comparisons, follow-up after discontinuation and prespecified interaction results for normal-B12 populations/subgroups
Further research: Define dose, post-discontinuation follow-up and subgroup questions separately, then assess the corresponding direct comparisons and interaction results.
Remaining uncertainty: The direct evidence required for extensions beyond the selected scope was not verified. No new mandatory conditions were added to the original score comparison.
Conditions for verification: Distinguish 1000 µg/day for 12 months in the selected low-B12 population from extensions concerning dose, post-discontinuation follow-up and normal B12.
Why this condition is needed: Needed to avoid extending the main effect to an optimal dose, permanent effect or effects at all B12 levels.
Application exceptions: Do not make every dose, discontinuation or normal-B12 study mandatory for the narrow original question. Do not determine an optimal dose solely from S06's active-dose title.
Referenced methods: M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed; M03 §3.2.1; detailed population criteria are internally designed — An internally developed, item-specific adaptation for Dose, persistence and subgroups. No official methodological tool was applied or certification performed.

Related sources S01 S06

N39 · Are NRS, replacement of analgesics and clinical events being required for this score question?

Current findings: Direct results for mean pain NRS/VAS, replacement of analgesics and clinical events are not imposed as additional mandatory conditions for the currently selected painDETECT score question. Those extended efficacy claims were not verified, and the manuscript does not extend the result to a general analgesic effect.
Verification status: Not applicable
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: A requirement to impose studies of other clinical questions as mandatory for the current narrow score comparison does not apply. This does not eliminate unread or unverified material.
Reason for missing information: Direct effects and intervals for mean NRS, medication replacement and clinical events remain unverified as separate questions.
Required materials and conditions: Interpretive boundaries of the selected question and corresponding direct clinical results if the claim is extended
Materials to obtain first: Interpretive boundaries of the selected question and corresponding direct clinical results if the claim is extended
Further research: When extending the question to mean pain, medication replacement or clinical events, define and assess separate populations, endpoints, comparators and direct results.
Remaining uncertainty: A requirement to impose studies of other clinical questions as mandatory for the current narrow score comparison does not apply. This does not eliminate unread or unverified material.
Conditions for verification: Distinguish the selected painDETECT score itself from separate questions about mean pain NRS, replacement of analgesics and clinical events.
Why this condition is needed: Needed to avoid unconditionally requiring studies of other clinical questions for the narrow score question.
Application exceptions: Does not apply does not mean that other clinical outcomes were verified. Mean pain intensity and replacement of analgesics remain unverified.
Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim — An internally developed, item-specific adaptation for Other clinical questions. No official methodological tool was applied or certification performed.

Related sources S01 S04

N40 · Were the stored summary, historical full-text reading and current unread status distinguished?

Current findings: What was actually read in this exercise was the Korean text, structure, evidence, citations and historical records in the current case 3111 stored summary. Historical access_level values for the S01 PDF, S04 author-hosted web full text, official/manufacturer documents and other materials are preserved as manuscript records. Access to external originals, the registration, prior record 110, and older ZIP/audit/calculation logs was not attempted in this exercise; they were neither acquired nor read. Report-specific actual access dates are null because the original citations do not provide them.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The distinction between actual summary reading and historical/current access to each material was documented. External source content was not newly verified.
Reason for missing information: Current original bytes of external or older separate source materials, and actual access dates for individual materials, are unverified.
Required materials and conditions: Exact locations in retained summaries, physical material types, historical access, current acquisition/reading and dates
Materials to obtain first: Exact locations in retained summaries, physical material types, historical access, current acquisition/reading and dates
Further research: Record each material's identity, original location, access events and acquisition/reading separately, and distinguish summary links from external links when comparing them.
Remaining uncertainty: The distinction between actual summary reading and historical/current access to each material was documented. External source content was not newly verified.
Conditions for verification: Separate actual reading of the current stored summary from each material's historical access, lack of original bytes and unattempted access in this exercise.
Why this condition is needed: Needed to avoid upgrading full-text access recorded in an original citation to full-text reading in this exercise.
Application exceptions: Leave missing report-specific access dates null. Do not infer access dates from the global verified_date.
Referenced methods: M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design — An internally developed, item-specific adaptation for Actual reading. No official methodological tool was applied or certification performed.

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

N41 · Is the review of 2026-09-16 being read as a current exhaustive search?

Current findings: The evidence reference date is 2026-09-16, and the review date for this conversion is 2026-10-05. evidence_status records verification of direct human evidence and eligible comparisons within the historical ChatGPT search scope, but absence_proven is false. The current corrections list is empty; no new search or correction/retraction lookup was performed in this exercise.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The historical search scope and current conversion scope were linked, but no current exhaustive search or correction check was performed.
Reason for missing information: No new search or exhaustive check of current corrections/retractions and unpublished/registered materials was performed.
Required materials and conditions: Historical search scope, list of unverified matters, correction/retraction records and reasons for updates
Materials to obtain first: Historical search scope, list of unverified matters, correction/retraction records and reasons for updates
Further research: During an authorized update, compare the historical search scope with the scope of new materials, and link corrections, retractions and unpublished/registered records to original reports.
Remaining uncertainty: The historical search scope and current conversion scope were linked, but no current exhaustive search or correction check was performed.
Conditions for verification: Distinguish the evidence reference date, the review date for this conversion, the historical search scope and the absence of a new search.
Why this condition is needed: Needed to avoid exaggerating a check of stored materials into a current search of all literature or a guarantee of completeness.
Application exceptions: Do not present the absence of a new search as proof of 0 studies, an effect of 0 or no new corrections.
Referenced methods: M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Scope of searches and corrections. No official methodological tool was applied or certification performed.

Related sources S01 S03 S05 S06 S11 S12

N42 · Have C, 46 and the existing EX/CX been turned into verdicts produced by this new table?

Current findings: The original verdict is C, 46 points, with B/P/R1/I1/EX/B2/CX. The manuscript's reruns of the calculator and scoring table are historical records; they were not rerun in this exercise. formal_adjusted_CI and some auxiliary axis fields are null, not 0. The existing −2.9/−3.8 are historical descriptive values; this table creates no new grade, effect or score.
Verification status: Met
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The original values, the historical nature of the calculations and the meaning of null values were preserved. No clinical reassessment or official methodological certification was performed.
Reason for missing information: Original bytes of the original ZIP/audit/calculation logs were not read in this exercise, and the gaps in the adjusted coefficient and CI remain.
Required materials and conditions: Original grade, score, axes, null values, sources of existing calculations and reasons for unverified information
Materials to obtain first: Original grade, score, axes, null values, sources of existing calculations and reasons for unverified information
Further research: Preserve the original assessment inputs, historical calculations and correction records to distinguish original values from new evidence events, and compare before and after an authorized revision.
Remaining uncertainty: The original values, the historical nature of the calculations and the meaning of null values were preserved. No clinical reassessment or official methodological certification was performed.
Conditions for verification: Preserve the original grade/score, 7 axes, null values and references to existing calculations, distinguishing them from statuses in the unscored evidence-gap table.
Why this condition is needed: Needed to avoid automatically carrying the existing assessment over as new table scores, efficacy probabilities or fulfillment of criteria.
Application exceptions: Do not rerun the original calculator or precedents in this exercise. Link the original C, 46, EX, CX and null values only as historical source values.
Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design — An internally developed, item-specific adaptation for Original verdict and historical calculations. No official methodological tool was applied or certification performed.

Related sources

N43 · Is historical deployment metadata being read as completed publication of this table?

Current findings: The original first_published_at is null and publication_status is ready_with_uncertainty. The record also contains server_deployed=true, server_write_performed=false and deployed_at=2026-09-16. These different historical metadata statements are not read as completed public release of the current table; original values and the policy of revisions under the same ID/URL are preserved.
Verification status: Partly verified
Materials actually read: Summary read: the actual locations and values in the current retained summary for case 3111 were read. Access to external or older separate source materials was not attempted in this exercise; they were neither acquired nor read
Why unverified: The original metadata statements and event boundaries were linked. Actual historical deployment receipts and website publication in this exercise were not verified.
Reason for missing information: Comparison of actual historical deployment events, the initial public-release time and a publication receipt for the current table are unverified.
Required materials and conditions: Original ID, canonical URL, initial-publication/server metadata and revision policy/history
Materials to obtain first: Original ID, canonical URL, initial-publication/server metadata and revision policy/history
Further research: Compare receipts for each publication event and actual public-release times with original metadata and revision history, preserving the full before-and-after content under the same ID/URL.
Remaining uncertainty: The original metadata statements and event boundaries were linked. Actual historical deployment receipts and website publication in this exercise were not verified.
Conditions for verification: Distinguish events in the existing ID/URL and publication/server metadata from this creation and future website posting.
Why this condition is needed: Needed to avoid using historical metadata statements as evidence of public release in this exercise.
Application exceptions: Do not arbitrarily correct original values such as server_deployed=true, server_write_performed=false and first_published_at=null. For this creation, published is false.
Referenced methods: M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design — An internally developed, item-specific adaptation for Publication metadata and updates. No official methodological tool was applied or certification performed.

Related sources