{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3111-main", "verdict_number": "3111", "title": "Oral dispersible methylcobalamin (vitamin B12) × Reduction in reported painDETECT score in metformin-treated diabetic neuropathy with low B12", "view_version": "1.0", "view_created_date": "2026-11-05", "criteria_version": "NGM-v3111-METHYL-B12-METFORMIN-PAINDETECT12M-1.0", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-16", "review_scope": { "materials_read": "Stored Korean and English manuscripts and case-specific criteria and application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "No new external clinical abstracts, full texts, registrations or analysis plans were read. Reading stored summaries is distinguished from not reading external source materials; the original verdict, numerical values and unverified information are preserved. No new searches, calculations or reassessment were performed.", "date_meaning": "This is the date the stored materials were checked, not the date of an up-to-date clinical literature search." }, "claim_context": { "population": "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", "intervention": "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", "endpoint": "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", "excluded_extensions": [ "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" ] }, "requirements": [ { "item_id": "N01", "question_type": "Separate question", "question": "Which population and which 12-month score are being compared?", "needed": "The original question and specifications of the population, ingredient, route, dose, comparator, time point and endpoint", "role": "Required", "role_reason": "The B12 effects discussed across the page must be distinguished from the selected score comparison.", "application_exception": "The actual subclaims list is empty. Mean pain NRS, all diabetic neuropathy and replacement of analgesics are not added as new subclaims.", "criterion": "Link the population, methylcobalamin, placebo and 12-month painDETECT comparison in the original /ko/effect and fixed question.", "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed — An internally developed, item-specific adaptation for Separate question. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Fix the original question and eligibility criteria, then separately examine only comparisons involving the same population, formulation and score.", "current_reports": [ "S01", "S04" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Met", "status_reason": "The identity and exclusions of the original question were verified. This does not mean that efficacy or a general analgesic effect has been established.", "missingness": "Pain entry criteria, the exact scale version and the adjusted effect estimate remain unverified in separate rows.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "The original question and specifications of the population, ingredient, route, dose, comparator, time point and endpoint" }, { "item_id": "N02", "question_type": "Active ingredient", "question": "Was methylcobalamin the trial's single active ingredient?", "needed": "The original trial's active ingredient, chemical form and whether it was a combination product", "role": "Required", "role_reason": "Needed to avoid combining effects of different chemical forms or combination products solely on the basis of the name B12.", "application_exception": "Cyanocobalamin, hydroxocobalamin and B-vitamin combinations are not direct evidence for this single-ingredient methylcobalamin comparison.", "criterion": "Identify methylcobalamin/mecobalamin as the actual added ingredient and distinguish it from other cobalamins.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Met", "status_reason": "The retained identity of the chemical form and single added ingredient was verified. Product purity and the trial batch were not verified.", "missingness": "The historical manufacturing batch and purity are unverified.", "uncertainty": "The retained identity of the chemical form and single added ingredient was verified. Product purity and the trial batch were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "The original trial's active ingredient, chemical form and whether it was a combination product" }, { "item_id": "N03", "question_type": "Trial product", "question": "Do the supply identity and historical batch of B12 fix match?", "needed": "Trial-product supply records, batch/purity documentation and the current product description", "role": "Required", "role_reason": "Needed to avoid treating the current product page as verification of the historical trial batch.", "application_exception": "Linking the UNI-PHARMA name and B12 fix page does not independently confirm the historical batch, purity or efficacy.", "criterion": "Record the trial product name and supplier, the current manufacturer description, and historical batch and purity separately.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Obtain the trial supply records and contemporaneous batch documentation, and compare them with the current product description while distinguishing their dates.", "current_reports": [ "S01", "S10" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "Only the product name and supplier were linked. Comparison of the batch, purity and identity with the current product remains outstanding.", "missingness": "Historical trial-batch, purity and manufacturing-source documentation is absent.", "uncertainty": "Only the product name and supplier were linked. Comparison of the batch, purity and identity with the current product remains outstanding.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Trial-product supply records, batch/purity documentation and the current product description" }, { "item_id": "N04", "question_type": "Route of administration", "question": "Has the oral dispersible formulation been reinterpreted as sublingual or injectable?", "needed": "Trial administration method and oral dispersible formulation specifications", "role": "Required", "role_reason": "A formulation that disperses in the mouth cannot be assumed to have the same administration route as sublingual holding or injection.", "application_exception": "Do not add a sublingual holding time, injection route or absorption mechanism absent from the source material.", "criterion": "Preserve the actual oral dispersible formulation and route without filling in an unreported sublingual holding time.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare the contemporaneous administration instructions to distinguish the dosing procedure from the actual route.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "The actual formulation is an oral dispersible tablet. No sublingual holding time is inferred and no injection route is substituted.", "condition_status": "Met", "status_reason": "The retained identity of the oral formulation and route was linked. Detailed dosing procedures or absorption mechanisms were not verified.", "missingness": "A sublingual holding time is not inferred from the manuscript, and historical batch details are unverified.", "uncertainty": "The retained identity of the oral formulation and route was linked. Detailed dosing procedures or absorption mechanisms were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Trial administration method and oral dispersible formulation specifications" }, { "item_id": "N05", "question_type": "Nominal dose", "question": "Has the trial dose been distinguished from total exposure?", "needed": "Trial dose and frequency, dietary/additional supplementation exposure and adherence records", "role": "Required", "role_reason": "Needed to avoid turning the trial's nominal dose into an individual dosing instruction or actual total intake.", "application_exception": "1000 µg/day is a trial condition, not an instruction for personal use or a change in diabetes medication.", "criterion": "Distinguish the trial dose of 1000 µg 1 time daily from total exposure including diet and additional supplementation.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Nominal dose. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare administration, additional supplementation and dietary records by group to assess differences between nominal dose and actual exposure.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The nominal trial dose and frequency were linked, but actual total exposure and adherence were not verified.", "missingness": "Exposure from diet, fortified foods and additional supplements, and numerical adherence, are unverified.", "uncertainty": "The nominal trial dose and frequency were linked, but actual total exposure and adherence were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Trial dose and frequency, dietary/additional supplementation exposure and adherence records" }, { "item_id": "N06", "question_type": "Conflicting product units", "question": "Has the manufacturer's 1000 µg versus 1000 mg labeling been resolved?", "needed": "Locations of the manufacturer's labels, corrections and contemporaneous trial-dose documentation", "role": "Required", "role_reason": "Needed to avoid silently harmonizing conflicting product units or substituting them for the trial dose.", "application_exception": "The conflict on the current product page does not justify changing the original trial's 1000 µg/day to 1000 mg/day.", "criterion": "Preserve both printed units on the current product page and handle them separately from the trial dose.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_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.", "current_reports": [ "S01", "S10" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Conflicting information", "status_reason": "The manuscript explicitly records inconsistent units on the same product page. Which label, if any, was corrected was not checked in this exercise.", "missingness": "A correction resolving the current product-label conflict and comparison with the historical batch are unverified.", "uncertainty": "The manuscript explicitly records inconsistent units on the same product page. Which label, if any, was corrected was not checked in this exercise.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Locations of the manufacturer's labels, corrections and contemporaneous trial-dose documentation" }, { "item_id": "N07", "question_type": "Observation period", "question": "Has 12-month administration been separated from results over other durations?", "needed": "Trial administration and assessment times, and the duration of each adjacent study", "role": "Required", "role_reason": "Studies cannot be counted as direct replications when durations and measurements differ, even if they use the same neuropathy label.", "application_exception": "The 4-month nerve-conduction result in S05 is a different outcome from this 12-month painDETECT comparison.", "criterion": "Link the selected score's 12-month time point and administration period without combining the adjacent 4-month result with it.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed — An internally developed, item-specific adaptation for Observation period. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare the original time-specific tables and trial schedule to separate administration duration, observation duration and the time point of the selected outcome.", "current_reports": [ "S01", "S05" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Met", "status_reason": "The selected time point and duration were linked, with the timing of adjacent results distinguished. The preregistered primary time point remains separately unverified.", "missingness": "Registered assessment times and follow-up after discontinuation are unverified.", "uncertainty": "The selected time point and duration were linked, with the timing of adjacent results distinguished. The preregistered primary time point remains separately unverified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Trial administration and assessment times, and the duration of each adjacent study" }, { "item_id": "N08", "question_type": "Population selection", "question": "Which adults with diabetic neuropathy were selected?", "needed": "Population diagnoses, duration of metformin use and B12 eligibility criterion", "role": "Required", "role_reason": "Needed to avoid automatically applying the results to all patients with diabetic neuropathy.", "application_exception": "Do not extend the selected population with low B12 and long-term metformin use to diabetes generally or to populations with normal B12.", "criterion": "Link the actual selection criteria: type 2 diabetes, confirmed peripheral and autonomic neuropathy, metformin for ≥4 years and low B12.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare inclusion/exclusion documentation and baseline characteristics to assess the applicability boundaries of the narrowly selected population.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The core population-selection criteria were preserved, but the pain threshold for entry and minimum duration were not verified.", "missingness": "Pain entry criteria, minimum duration and detailed implementation of selection are unverified.", "uncertainty": "The core population-selection criteria were preserved, but the pain threshold for entry and minimum duration were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Population diagnoses, duration of metformin use and B12 eligibility criterion" }, { "item_id": "N09", "question_type": "Low-B12 boundary", "question": "Is B12 <400 pmol/L being interpreted as absolute deficiency in everyone?", "needed": "Baseline B12 criterion, diagnosis of deficiency and population-specific results", "role": "Required", "role_reason": "A low eligibility value and correction of confirmed deficiency are different questions of applicability.", "application_exception": "Do not classify every participant as having confirmed absolute deficiency solely on the basis of B12 <400 pmol/L.", "criterion": "Distinguish the trial's low-B12 criterion from confirmed absolute deficiency and the effects of supplementation in people with normal B12.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare diagnostic evidence of deficiency with the eligibility value, and assess extension to a normal-B12 population through a separate comparison.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The low-B12 selection boundary was linked, but diagnoses of absolute deficiency and effects in a normal-B12 population were not verified.", "missingness": "Individual deficiency diagnoses, baseline distribution and direct comparisons in a normal-B12 population are unverified.", "uncertainty": "The low-B12 selection boundary was linked, but diagnoses of absolute deficiency and effects in a normal-B12 population were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Baseline B12 criterion, diagnosis of deficiency and population-specific results" }, { "item_id": "N10", "question_type": "Pain entry criteria", "question": "Were the pain NRS entry threshold and minimum duration verified?", "needed": "Pain diagnosis, entry NRS criterion and minimum duration in the eligibility documentation", "role": "Required", "role_reason": "The description 'painful' alone does not establish a population with a particular pain intensity or duration of chronic pain.", "application_exception": "Do not reinterpret unverified entry criteria as a population without pain or absence of analgesic efficacy.", "criterion": "Distinguish the description of painful neuropathy from the verification status of the exact pain threshold and duration for entry.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare the eligibility documentation and diagnostic procedures to verify actual pain-intensity and duration entry criteria.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "The authors' description of painful neuropathy is preserved, but the entry NRS criterion and minimum pain duration are unverified.", "condition_status": "Unverified", "status_reason": "The exact pain entry criteria cannot be established within the retained material read. This does not mean that participants did not experience pain.", "missingness": "Documentation of the pain NRS entry threshold, minimum duration and diagnostic implementation is absent.", "uncertainty": "The exact pain entry criteria cannot be established within the retained material read. This does not mean that participants did not experience pain.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Pain diagnosis, entry NRS criterion and minimum duration in the eligibility documentation" }, { "item_id": "N11", "question_type": "Glycemic-status selection", "question": "Was selection for stable HbA1c of 6.5–7.5% preserved?", "needed": "Baseline glycemic status, stability criteria and glycemic-medication records by group", "role": "Required", "role_reason": "Needed to avoid applying the result of adjunctive treatment on stable glycemic management to all glycemic states.", "application_exception": "A nonsignificant result for HbA1c change is not a direct substitute for this stable-range selection criterion or the painDETECT result.", "criterion": "Link the stable HbA1c range with the population receiving common glycemic management.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare baseline glycemic selection criteria and management/medication records by group to assess applicability and concomitant-treatment boundaries.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The retained stability criterion and range were linked, but details of actual glycemic-medication changes and management by group are lacking.", "missingness": "Detailed records of actual glycemic-medication changes and management exposure by group are unverified.", "uncertainty": "The retained stability criterion and range were linked, but details of actual glycemic-medication changes and management by group are lacking.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Baseline glycemic status, stability criteria and glycemic-medication records by group" }, { "item_id": "N12", "question_type": "Placebo specifications", "question": "Was the full composition of the similar-looking placebo verified?", "needed": "Placebo appearance, composition and batch, and common management in each group", "role": "Required", "role_reason": "Needed to avoid confusing similar appearance with complete placebo identity or biological inactivity.", "application_exception": "Do not conclude that the placebo was an active treatment or that blinding was broken because its full composition is unverified.", "criterion": "Record the similar-looking placebo comparison separately from the unverified full excipient composition.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; 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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare contemporaneous placebo specifications and manufacturing records to assess comparator composition and implementation of blinding.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "The comparator conditions are a similar-looking placebo and stable common glycemic management. Full placebo excipients and the historical batch are unverified.", "condition_status": "Partly verified", "status_reason": "The framework of the placebo comparison was linked, but full composition and batch identity were not verified.", "missingness": "Documentation of full placebo excipients, batch and implementation of blinding is unverified.", "uncertainty": "The framework of the placebo comparison was linked, but full composition and batch identity were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Placebo appearance, composition and batch, and common management in each group" }, { "item_id": "N13", "question_type": "Common treatment", "question": "Were common glycemic management and adjustment variables distinguished?", "needed": "Glycemic medications and management changes by group, and ANCOVA adjustment specifications", "role": "Required", "role_reason": "Needed to avoid using a common policy as proof that all actual treatments were identical.", "application_exception": "Do not indicate that all differences in concomitant treatment, confounding and adherence were resolved merely because adjustment variables were used.", "criterion": "Record the common management policy, actual treatment changes by group, and adjustment for HbA1c/glycemic medications separately.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare concomitant-treatment changes by group and analysis specifications to assess the selected intervention's contribution and the effect of interest.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The policy and adjustment variables were linked, but detailed comparison of actual concomitant exposure by group and the handling of changes remains outstanding.", "missingness": "Glycemic-medication changes by group, details of the adjustment model and specification of the effect of interest are unverified.", "uncertainty": "The policy and adjustment variables were linked, but detailed comparison of actual concomitant exposure by group and the handling of changes remains outstanding.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Glycemic medications and management changes by group, and ANCOVA adjustment specifications" }, { "item_id": "N14", "question_type": "Rescue analgesics", "question": "Is the policy permitting paracetamol the same as actual use?", "needed": "Rescue-analgesic policy, amount used and changes by group, and handling in the analysis", "role": "Required", "role_reason": "A permission rule alone cannot establish that actual analgesic exposure was identical between groups.", "application_exception": "Do not interpret the policy restricting analgesics as an effect replacing analgesics, or fill in actual use as 0.", "criterion": "Distinguish restrictions on other analgesics and occasional paracetamol permitted for 2–3 days from the actual amounts used by group.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare rescue-medication use records by group to assess the relationship between the score comparison and concurrent treatment.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "The retained policy restricted other analgesics and permitted occasional paracetamol for only 2–3 days. The actual amount of rescue medication used is unverified.", "condition_status": "Partly verified", "status_reason": "The analgesic policy was verified, but actual amounts used by group and handling in the analysis were not verified.", "missingness": "Data on the amount and frequency of paracetamol use by group and handling in the analysis are unverified.", "uncertainty": "The analgesic policy was verified, but actual amounts used by group and handling in the analysis were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Rescue-analgesic policy, amount used and changes by group, and handling in the analysis" }, { "item_id": "N15", "question_type": "Adherence and diet", "question": "Were numerical adherence and additional B12 exposure verified?", "needed": "Dosing records and numerical adherence by group, and records of diet, fortified foods and additional supplementation", "role": "Required", "role_reason": "Needed because reported completion by everyone differs from actual adherence.", "application_exception": "Do not substitute 90 fully adherent participants or identical total intake for the 90 reported completers.", "criterion": "Distinguish nominal administration from actual dosing, diet, fortified foods and other supplementation exposure.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — An internally developed, item-specific adaptation for Adherence and diet. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare dosing, diet and additional-exposure records, and assess their handling in relation to the effect of interest.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Unverified", "status_reason": "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.", "missingness": "Numerical adherence, diet and additional-supplement exposure data by group are lacking.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Dosing records and numerical adherence by group, and records of diet, fortified foods and additional supplementation" }, { "item_id": "N16", "question_type": "Scale definition", "question": "Is the painDETECT total score a mean pain-intensity NRS?", "needed": "Original scale definition, total-score components, range and direction", "role": "Required", "role_reason": "Needed to avoid elevating a screening total score to a reduction in mean pain NRS/VAS.", "application_exception": "Preserve the scale's original screening purpose while retaining the comparison of the patient-reported score itself selected for this page.", "criterion": "Distinguish the screening composite of sensory qualities, pain course and radiation from items recording pain intensity.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4; 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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_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.", "current_reports": [ "S01", "S04" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Met", "status_reason": "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.", "missingness": "The exact questionnaire language/version used in the trial and clinical importance are unverified.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original scale definition, total-score components, range and direction" }, { "item_id": "N17", "question_type": "Questionnaire implementation", "question": "Were the trial questionnaire's language, version and recall period verified?", "needed": "Trial questionnaire, language/translation, version, recall period and scoring procedure", "role": "Required", "role_reason": "The original scale definition does not verify all aspects of how measurement was actually implemented in the trial.", "application_exception": "Do not infer the trial questionnaire version or recall period from the original scale's total-score range.", "criterion": "Distinguish the original scale description from the verification status of the language, version and recall period actually used in the trial.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application — An internally developed, item-specific adaptation for Questionnaire implementation. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare the contemporaneous questionnaire and scoring procedure with the original scale definition to assess how the actual measurement corresponds to it.", "current_reports": [ "S01", "S04" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Unverified", "status_reason": "The trial's measurement implementation cannot be established from the stored materials read. This is not a judgment that the scale is invalid.", "missingness": "The questionnaire language, version, recall period and scoring procedure are unverified.", "uncertainty": "The trial's measurement implementation cannot be established from the stored materials read. This is not a judgment that the scale is invalid.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Trial questionnaire, language/translation, version, recall period and scoring procedure" }, { "item_id": "N18", "question_type": "Selected time point", "question": "Was the page's primary endpoint at 12 months distinguished from a registered primary (1st) endpoint?", "needed": "Outcome time points, original registration hierarchy, initial posting and amendment history", "role": "Required", "role_reason": "Needed to avoid automatically turning the page's primary endpoint into a preregistered primary (1st) outcome.", "application_exception": "Do not reinterpret an unverified registration hierarchy as confirmed absence of registration or confirmed selective reporting.", "criterion": "Record the reported score at 12 months selected for this page separately from the verification status of the preregistered primary endpoint.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application — An internally developed, item-specific adaptation for Selected time point. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare the initial registration and timing of outcome reporting to assess how selection occurred and why changes were made.", "current_reports": [ "S01", "S03" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The reported time point and the page's selection were verified, but the preregistered hierarchy could not be compared.", "missingness": "The registration's initial posting, amendment history and pain-endpoint hierarchy are unverified.", "uncertainty": "The reported time point and the page's selection were verified, but the preregistered hierarchy could not be compared.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Outcome time points, original registration hierarchy, initial posting and amendment history" }, { "item_id": "N19", "question_type": "Allocation and blinding", "question": "Was the RCT designation distinguished from implementation of allocation concealment?", "needed": "Original trial design, allocation/concealment, implementation of blinding and baseline data", "role": "Required", "role_reason": "Needed because a design designation alone cannot establish absence of allocation or measurement bias.", "application_exception": "Do not present unreported implementation of allocation concealment as actual concealment failure or an established magnitude of bias.", "criterion": "Link the randomized, placebo-controlled, double-blind design and the unreported implementation of allocation concealment to each outcome.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare allocation procedures, placebo specifications and assessment-blinding documentation to assess potential bias in the selected score.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The design designation and limitations in the original assessment were linked. Detailed implementation was not compared, and no new bias-assessment tool was applied.", "missingness": "Detailed source documentation of allocation concealment and implementation of blinding is unverified.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original trial design, allocation/concealment, implementation of blinding and baseline data" }, { "item_id": "N20", "question_type": "Allocation and completion", "question": "Are allocation of 90 participants, 44/46 by group, and completion being read as analysis denominators?", "needed": "Flow diagram and denominators for allocation, completion, measurement and analysis by group", "role": "Required", "role_reason": "Needed to avoid automatically using a statement that everyone completed the trial as the analysis denominator for each outcome.", "application_exception": "Do not treat the 90 reported completers as a verified painDETECT analysis n=90 or group-specific n=44/46.", "criterion": "Preserve allocation and reported completion of 44/46 separately from endpoint-specific analysis denominators.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Allocation and completion. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare the flow diagram and endpoint-specific analysis tables to link participant counts for allocation → completion → measurement → analysis.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The retained allocation and completion values were linked, but the actual painDETECT analysis denominators were not verified.", "missingness": "Endpoint-specific measurement and analysis denominators and documentation of exclusions/missing-data handling are unverified.", "uncertainty": "The retained allocation and completion values were linked, but the actual painDETECT analysis denominators were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Flow diagram and denominators for allocation, completion, measurement and analysis by group" }, { "item_id": "N21", "question_type": "Analysis population and missing data", "question": "Were the painDETECT analysis population and missing-data handling verified?", "needed": "PainDETECT analysis denominators by group, analysis population, reasons for missing data/exclusions and their handling", "role": "Required", "role_reason": "Needed to avoid filling in absent analysis populations and denominators as ITT or all completers.", "application_exception": "Do not arbitrarily label an unreported analysis population as ITT/PP or fill in dropouts and missing data as 0.", "criterion": "Distinguish endpoint-specific analysis populations, ITT/PP and missing-data handling from reported completion.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Analysis population and missing data. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare outcome-specific analysis specifications and missing-data/exclusion records to assess the effect of interest and the actual analysis population.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Unverified", "status_reason": "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.", "missingness": "Exact analysis n, ITT/PP, reasons for missing data/exclusions and handling specifications are unverified.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "PainDETECT analysis denominators by group, analysis population, reasons for missing data/exclusions and their handling" }, { "item_id": "N22", "question_type": "Original scores and descriptive differences", "question": "Are the original scores, existing change contrast and endpoint difference being read as the same estimate?", "needed": "Scores and time points in the original results table, definitions of existing descriptive differences and adjusted results", "role": "Required", "role_reason": "Needed to avoid confusing within-group change, between-group difference in change, endpoint difference and an adjusted coefficient.", "application_exception": "Do not present the existing −2.9 and −3.8 as new calculations or unreported adjusted estimates.", "criterion": "Preserve 18.4→17.1 versus 19.3→20.9 and the manuscript's descriptive values of −2.9/−3.8 separately.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application — An internally developed, item-specific adaptation for Original scores and descriptive differences. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare the original table and analysis definitions to assess the correspondence among original scores, descriptive differences and the formal adjusted effect.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Met", "status_reason": "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.", "missingness": "The formal adjusted coefficient, SE, CI and endpoint-specific analysis denominators are unverified.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Scores and time points in the original results table, definitions of existing descriptive differences and adjusted results" }, { "item_id": "N23", "question_type": "Adjusted effect and interval", "question": "Has P<0.001 been turned into an adjusted coefficient, SE or CI?", "needed": "ANCOVA specifications, adjusted coefficient, SE, CI, denominators and results table", "role": "Required", "role_reason": "Needed to avoid establishing effect magnitude or precision from statistical significance alone.", "application_exception": "P<0.001 is not an exact P value; no adjusted CI or standardized effect is newly back-calculated.", "criterion": "Link the formal ANCOVA comparison of change, adjustment variables and reported P separately from the unreported coefficient/SE/CI.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application — An internally developed, item-specific adaptation for Adjusted effect and interval. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare formal model output and the results table to verify the formal effect of interest, interval and denominators.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The formal analysis type, adjustment variables and P reported as an inequality were linked. The formal effect magnitude and interval were not verified.", "missingness": "The adjusted coefficient, SE, CI, exact analysis denominators and model output are unverified.", "uncertainty": "The formal analysis type, adjustment variables and P reported as an inequality were linked. The formal effect magnitude and interval were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "ANCOVA specifications, adjusted coefficient, SE, CI, denominators and results table" }, { "item_id": "N24", "question_type": "Conflicting baseline SD", "question": "Have the baseline SD values of 9.2 and 9.7 been silently harmonized?", "needed": "Locations of baseline SD in the original Table 4 and text, corrections, and group/time-point specifications", "role": "Required", "role_reason": "Needed to avoid arbitrarily selecting or correcting conflicting variability values, or using them as established inputs for a CI calculation.", "application_exception": "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.", "criterion": "Retain the conflict between the two baseline SD values reported in the retained manuscript and their unresolved attribution.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Conflicting information", "status_reason": "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.", "missingness": "Exact table cells, group/time-point attribution and correction history are unverified.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Locations of baseline SD in the original Table 4 and text, corrections, and group/time-point specifications" }, { "item_id": "N25", "question_type": "Clinical importance", "question": "Is there an applicable MCID for painDETECT change in this population?", "needed": "Evidence for an MCID applicable to this population, scale version and change estimate", "role": "Required (for interpreting clinical importance)", "role_reason": "Needed to avoid elevating a statistically significant score difference to a clinically important mean analgesic effect.", "application_exception": "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.", "criterion": "Distinguish a criterion for an important difference applicable to the selected score, population and time point from a diagnostic screening threshold.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare evidence on important change in the same population and scale version with the score definition, and interpret it alongside the reported interval.", "current_reports": [ "S01", "S04" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Unverified", "status_reason": "The clinical importance of the score change in the selected population cannot be established within the current scope.", "missingness": "An applicable MCID, scale implementation and formal effect interval are unverified.", "uncertainty": "The clinical importance of the score change in the selected population cannot be established within the current scope.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Evidence for an MCID applicable to this population, scale version and change estimate" }, { "item_id": "N26", "question_type": "Registration history", "question": "Was the identity of NCT04706377 distinguished from reading its content?", "needed": "Original registration record, initial posting, amendment history and outcome hierarchy", "role": "Required", "role_reason": "Needed to avoid turning the existence of a registration number into verification of a prespecified primary (1st) endpoint or registration timing.", "application_exception": "Do not present historical access classified as registration_shell_only as reading the full registration or as confirmation that the trial was unregistered.", "criterion": "Distinguish linking a registration number from obtaining the initial posting, amendment history and readable endpoint hierarchy.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare the initial registration and amendment history with outcome reporting to assess temporal order, the selected endpoint and reasons for changes.", "current_reports": [ "S01", "S03" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The registration identity is preserved, but comparison of the registration content and prespecified hierarchy remains incomplete.", "missingness": "The initial posting, amendment history, readable endpoint hierarchy and protocol/SAP are unverified.", "uncertainty": "The registration identity is preserved, but comparison of the registration content and prespecified hierarchy remains incomplete.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original registration record, initial posting, amendment history and outcome hierarchy" }, { "item_id": "N27", "question_type": "Plans and multiple endpoints", "question": "Were the protocol and SAP compared with the selection of actual results?", "needed": "Protocol, SAP, prespecified endpoints/analyses/time points, handling of multiple endpoints and reporting", "role": "Required", "role_reason": "Needed to expose the lack of materials for assessing whether only favorable scores were selected.", "application_exception": "Do not treat unavailable materials as confirmation of selective reporting or arbitrarily fill in primary_failed_secondary_positive as true/false.", "criterion": "Distinguish unavailable plans and unverified multiple-endpoint handling and prespecified hierarchy from confirmed selective reporting.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_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.", "current_reports": [ "S01", "S03" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Unverified", "status_reason": "Without a direct comparison of plans and reporting, prespecification, the circumstances of changes and handling of multiple endpoints are not established.", "missingness": "The protocol, SAP, handling of multiple endpoints and documentation of reasons for changes are unverified.", "uncertainty": "Without a direct comparison of plans and reporting, prespecification, the circumstances of changes and handling of multiple endpoints are not established.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Protocol, SAP, prespecified endpoints/analyses/time points, handling of multiple endpoints and reporting" }, { "item_id": "N28", "question_type": "Results without a significant difference", "question": "Were nonsignificant results for MNSIE and HbA1c preserved?", "needed": "All reported endpoints, denominators, time points and analyses, including favorable results and results without a significant difference", "role": "Required", "role_reason": "Other endpoints without a significant difference must be preserved alongside favorable scores, rather than retaining only favorable scores.", "application_exception": "Do not reinterpret nonsignificance as an effect of 0, equivalence or direct refutation of the painDETECT result.", "criterion": "Attribute P=0.607 and P=0.876 to their other endpoints separately from the selected painDETECT outcome.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Met", "status_reason": "The manuscript's other endpoints, results without a significant difference and attribution boundaries were preserved. Their full analyses and intervals were not verified.", "missingness": "Detailed denominators, analyses and intervals for the two endpoints are unverified in the current summary.", "uncertainty": "The manuscript's other endpoints, results without a significant difference and attribution boundaries were preserved. Their full analyses and intervals were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "All reported endpoints, denominators, time points and analyses, including favorable results and results without a significant difference" }, { "item_id": "N29", "question_type": "Same-trial family", "question": "Are S01, S02 and S03 being counted as three replications?", "needed": "DOI, PMID, PMCID, registration number and report-family linkage", "role": "Required", "role_reason": "Needed to avoid converting the number of article, bibliographic and registration reports into a count of unique trials.", "application_exception": "Do not delete bibliographic/registration records because they lack separate results, or add linked records as new independent trials.", "criterion": "Link the original trial, NLM bibliographic record and registration number within F01, distinguishing them from independent replication.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare identifiers, trial numbers and original-report identities to link reports belonging to the same trial family.", "current_reports": [ "S01", "S02", "S03" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Met", "status_reason": "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.", "missingness": "Exhaustive comparison of all related reports and study families, and the total number of unique participants, remain undetermined.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "DOI, PMID, PMCID, registration number and report-family linkage" }, { "item_id": "N30", "question_type": "Adjacent 1992 trial", "question": "Are improvement and the absence of a significant nerve-conduction difference in S05 being read as replication of the same question?", "needed": "S05 original abstract, population/dose/scale, denominators, duration and results", "role": "Supplementary; required for a claim of exact replication", "role_reason": "Needed to avoid creating an exact painDETECT replication from favorable related symptom results alone.", "application_exception": "Do not substitute nonsignificant nerve-conduction results at 4 months for no effect on the selected 12-month painDETECT outcome.", "criterion": "Record F02's symptom improvement and nonsignificant nerve-conduction result at 4 months alongside the unverified selected score, population and dose.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare population, dose, measurements and denominators in the original abstract and full text to distinguish direct replication from adjacent symptom results.", "current_reports": [ "S05" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "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.", "missingness": "The same population, dose, scale, between-group scores, denominators and original full text are unverified.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "S05 original abstract, population/dose/scale, denominators, duration and results" }, { "item_id": "N31", "question_type": "2026 active-dose comparison", "question": "Is a comparison of 1000 versus 2000 µg a placebo-controlled replication?", "needed": "S06 population, chemical form, active doses, endpoints, denominators and full results", "role": "Supplementary; required for dose or replication claims", "role_reason": "A comparison of two active doses differs from the efficacy question of added B12 versus no supplementation.", "application_exception": "Do not automatically establish that oral B12 in the title means the exact methylcobalamin form, the same painDETECT endpoint or the same population.", "criterion": "Distinguish F03's comparison of two active doses from a placebo comparison without supplementation, without filling in unverified pain values.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare the original trial's population, chemical form, doses, comparator and endpoints, and assess dose comparison as a separate question.", "current_reports": [ "S06" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "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.", "missingness": "The original full text, numerical pain results, denominators and exact correspondence of chemical form/population are unverified.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "S06 population, chemical form, active doses, endpoints, denominators and full results" }, { "item_id": "N32", "question_type": "Reviews and discovery leads", "question": "Are S11 and S12 being counted as new independent replications?", "needed": "Reviews' included-study tables, original-trial identities, chemical forms/routes/endpoints and duplicate-report linkage", "role": "Supplementary; required for claims about overall replication", "role_reason": "Needed to avoid adding discovery citations to the number of independent trials addressing the same question.", "application_exception": "Do not use reviews of mixed B-vitamin types, routes and formulations as direct results for a single-ingredient methylcobalamin painDETECT comparison.", "criterion": "Distinguish review identities used for discovery from comparison of the actual inclusion and results of independent original trials.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Link the trials included in reviews to original reports, then individually compare family overlap, differences in conditions and unverified results.", "current_reports": [ "S11", "S12" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "Discovery identities and historical access limitations were linked. Comparison of included studies and families addressing the same question remains incomplete.", "missingness": "Review full texts, included-study tables, original-report families and results within the same boundaries are unverified.", "uncertainty": "Discovery identities and historical access limitations were linked. Comparison of included studies and families addressing the same question remains incomplete.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Reviews' included-study tables, original-trial identities, chemical forms/routes/endpoints and duplicate-report linkage" }, { "item_id": "N33", "question_type": "Funding and independence", "question": "Were product supply and no external funding reinterpreted as independent funding?", "needed": "Research funding, product/placebo supply, company role, COI and institutional/author declarations", "role": "Supplementary; required for independence claims", "role_reason": "Needed to avoid confusing in-kind product supply with funding and independent replication.", "application_exception": "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.", "criterion": "Preserve separately the scope of declarations of no external research funding, company product/placebo supply, no involvement and no COI.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare funding, supply, company roles and author declarations report by report, recording the scope of verification and omissions.", "current_reports": [ "S01" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The reported declarations were linked, but no verification by an independent institution or new exhaustive review of interests was performed.", "missingness": "Detailed contracts, author/institutional relationships and independent verification are unverified.", "uncertainty": "The reported declarations were linked, but no verification by an independent institution or new exhaustive review of interests was performed.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Research funding, product/placebo supply, company role, COI and institutional/author declarations" }, { "item_id": "N34", "question_type": "Trial reporting of harms", "question": "Is nonreporting of suspected B12-related AEs being read as 0 AEs of any kind?", "needed": "All AEs, SAEs, relatedness, discontinuations, collection methods, events/people and denominators/duration by group", "role": "Supplementary; required for safety interpretation", "role_reason": "Needed to avoid turning limited reporting of relatedness into absence of all events or verified safety.", "application_exception": "Do not substitute 0 AEs, SAEs or discontinuations for the report that everyone completed the trial, or newly calculate event rates.", "criterion": "Distinguish the report that no suspected B12-related adverse reactions were observed from all AEs/SAEs, discontinuations, denominators and the scope of collection.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare original safety tables and collection, relatedness and discontinuation records by group to distinguish people, events, duration and unreported information.", "current_reports": [ "S01", "S07", "S08", "S09" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The narrow scope of the original harms report was preserved. The complete event and discontinuation records, denominators and collection system were not verified.", "missingness": "All AEs, SAEs, discontinuations, collection methods, events/people and denominators by group, and long-term/special-population data, are unverified.", "uncertainty": "The narrow scope of the original harms report was preserved. The complete event and discontinuation records, denominators and collection system were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "All AEs, SAEs, relatedness, discontinuations, collection methods, events/people and denominators/duration by group" }, { "item_id": "N35", "question_type": "Official metformin document", "question": "Is the safety context of metformin and low B12 an analgesic effect?", "needed": "Population, scope of recommendations and original location in official document S07", "role": "Supplementary; required for safety and population interpretation", "role_reason": "Needed to avoid reversing an association between medication and B12 status into an analgesic effect of supplementation.", "application_exception": "Do not use the official monitoring document to justify a methylcobalamin painDETECT effect or an individual change in metformin.", "criterion": "Distinguish the MHRA risk-monitoring context from efficacy of the selected methylcobalamin intervention and individual medication changes.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Compare the official document's exposure, population and recommendations with the original trial question to distinguish safety context from efficacy claims.", "current_reports": [ "S07" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Met", "status_reason": "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.", "missingness": "Changes to the current official document and applicability to individuals were not checked in this exercise.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Population, scope of recommendations and original location in official document S07" }, { "item_id": "N36", "question_type": "Warnings for other chemical forms", "question": "Has the cobalt warning been repurposed as a methylcobalamin event rate?", "needed": "Specified products, chemical forms and scope of sensitivity reactions in official notice S08", "role": "Supplementary; required for extending harms claims", "role_reason": "Needed to avoid transferring warnings for other cobalamins to harm incidence in this trial or individual safety.", "application_exception": "Do not turn a cobalt-sensitivity warning into confirmation that methylcobalamin is risk-free, or that causality or frequency of harm is established.", "criterion": "Preserve the chemical-form and event scope of the warning explicitly naming hydroxocobalamin and cyanocobalamin.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_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.", "current_reports": [ "S08" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Met", "status_reason": "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.", "missingness": "Direct chemical-form-specific methylcobalamin events, denominators and individual applicability are unverified.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Specified products, chemical forms and scope of sensitivity reactions in official notice S08" }, { "item_id": "N37", "question_type": "UL and reused source", "question": "Does the ODS statement that no UL is established mean unlimited safety?", "needed": "Original S09 ODS text, actual content/review history of the excerpt from prior record 110, and long-term/special-population safety data", "role": "Supplementary; required for generalizing safety", "role_reason": "Needed because absence of a UL differs from a guarantee of safety at high doses, over the long term or in all populations.", "application_exception": "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.", "criterion": "Distinguish the inherited UL description and source-material review date from prior record 110 from actual reading in the current exercise.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_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.", "current_reports": [ "S09" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "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.", "missingness": "The current ODS original, original bytes of the prior record 110 excerpt and long-term/special-population harms data are unverified.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original S09 ODS text, actual content/review history of the excerpt from prior record 110, and long-term/special-population safety data" }, { "item_id": "N38", "question_type": "Dose, persistence and subgroups", "question": "Does this also answer optimal dose, persistence after stopping and effects in people with normal B12?", "needed": "Direct dose comparisons, follow-up after discontinuation and prespecified interaction results for normal-B12 populations/subgroups", "role": "Supplementary; required for the corresponding extended claims", "role_reason": "Needed to avoid extending the main effect to an optimal dose, permanent effect or effects at all B12 levels.", "application_exception": "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.", "criterion": "Distinguish 1000 µg/day for 12 months in the selected low-B12 population from extensions concerning dose, post-discontinuation follow-up and normal B12.", "basis": "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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Define dose, post-discontinuation follow-up and subgroup questions separately, then assess the corresponding direct comparisons and interaction results.", "current_reports": [ "S01", "S06" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Unverified", "status_reason": "The direct evidence required for extensions beyond the selected scope was not verified. No new mandatory conditions were added to the original score comparison.", "missingness": "Direct estimates for optimal dose, post-discontinuation follow-up and normal-B12 populations/subgroups are unverified.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Direct dose comparisons, follow-up after discontinuation and prespecified interaction results for normal-B12 populations/subgroups" }, { "item_id": "N39", "question_type": "Other clinical questions", "question": "Are NRS, replacement of analgesics and clinical events being required for this score question?", "needed": "Interpretive boundaries of the selected question and corresponding direct clinical results if the claim is extended", "role": "Does not apply to the current score question; required for extended claims", "role_reason": "Needed to avoid unconditionally requiring studies of other clinical questions for the narrow score question.", "application_exception": "Does not apply does not mean that other clinical outcomes were verified. Mean pain intensity and replacement of analgesics remain unverified.", "criterion": "Distinguish the selected painDETECT score itself from separate questions about mean pain NRS, replacement of analgesics and clinical events.", "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim — An internally developed, item-specific adaptation for Other clinical questions. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "When extending the question to mean pain, medication replacement or clinical events, define and assess separate populations, endpoints, comparators and direct results.", "current_reports": [ "S01", "S04" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Not applicable", "status_reason": "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.", "missingness": "Direct effects and intervals for mean NRS, medication replacement and clinical events remain unverified as separate questions.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Interpretive boundaries of the selected question and corresponding direct clinical results if the claim is extended" }, { "item_id": "N40", "question_type": "Actual reading", "question": "Were the stored summary, historical full-text reading and current unread status distinguished?", "needed": "Exact locations in retained summaries, physical material types, historical access, current acquisition/reading and dates", "role": "Required", "role_reason": "Needed to avoid upgrading full-text access recorded in an original citation to full-text reading in this exercise.", "application_exception": "Leave missing report-specific access dates null. Do not infer access dates from the global verified_date.", "criterion": "Separate actual reading of the current stored summary from each material's historical access, lack of original bytes and unattempted access in this exercise.", "basis": "M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design — An internally developed, item-specific adaptation for Actual reading. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_research": "Record each material's identity, original location, access events and acquisition/reading separately, and distinguish summary links from external links when comparing them.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S06", "S07", "S08", "S09", "S10", "S11", "S12" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Met", "status_reason": "The distinction between actual summary reading and historical/current access to each material was documented. External source content was not newly verified.", "missingness": "Current original bytes of external or older separate source materials, and actual access dates for individual materials, are unverified.", "uncertainty": "The distinction between actual summary reading and historical/current access to each material was documented. External source content was not newly verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Exact locations in retained summaries, physical material types, historical access, current acquisition/reading and dates" }, { "item_id": "N41", "question_type": "Scope of searches and corrections", "question": "Is the review of 2026-09-16 being read as a current exhaustive search?", "needed": "Historical search scope, list of unverified matters, correction/retraction records and reasons for updates", "role": "Required", "role_reason": "Needed to avoid exaggerating a check of stored materials into a current search of all literature or a guarantee of completeness.", "application_exception": "Do not present the absence of a new search as proof of 0 studies, an effect of 0 or no new corrections.", "criterion": "Distinguish the evidence reference date, the review date for this conversion, the historical search scope and the absence of a new search.", "basis": "M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed — An internally developed, item-specific adaptation for Scope of searches and corrections. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_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.", "current_reports": [ "S01", "S03", "S05", "S06", "S11", "S12" ], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The historical search scope and current conversion scope were linked, but no current exhaustive search or correction check was performed.", "missingness": "No new search or exhaustive check of current corrections/retractions and unpublished/registered materials was performed.", "uncertainty": "The historical search scope and current conversion scope were linked, but no current exhaustive search or correction check was performed.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Historical search scope, list of unverified matters, correction/retraction records and reasons for updates" }, { "item_id": "N42", "question_type": "Original verdict and historical calculations", "question": "Have C, 46 and the existing EX/CX been turned into verdicts produced by this new table?", "needed": "Original grade, score, axes, null values, sources of existing calculations and reasons for unverified information", "role": "Required (to preserve the original verdict)", "role_reason": "Needed to avoid automatically carrying the existing assessment over as new table scores, efficacy probabilities or fulfillment of criteria.", "application_exception": "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.", "criterion": "Preserve the original grade/score, 7 axes, null values and references to existing calculations, distinguishing them from statuses in the unscored evidence-gap table.", "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; 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.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_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.", "current_reports": [], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Met", "status_reason": "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.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original grade, score, axes, null values, sources of existing calculations and reasons for unverified information" }, { "item_id": "N43", "question_type": "Publication metadata and updates", "question": "Is historical deployment metadata being read as completed publication of this table?", "needed": "Original ID, canonical URL, initial-publication/server metadata and revision policy/history", "role": "Required (for tracking events)", "role_reason": "Needed to avoid using historical metadata statements as evidence of public release in this exercise.", "application_exception": "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.", "criterion": "Distinguish events in the existing ID/URL and publication/server metadata from this creation and future website posting.", "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design — An internally developed, item-specific adaptation for Publication metadata and updates. No official methodological tool was applied or certification performed.", "condition_origin": "An individually developed criterion designed after actually reading the current retained content for case 3111. This is neither a blinded exercise nor a new clinical preregistration.", "proposed_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.", "current_reports": [], "existence": "Exact locations and citation identities in the current retained summary for case 3111 verified; current public availability and original bytes of the source documents unverified", "acquired_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", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The original metadata statements and event boundaries were linked. Actual historical deployment receipts and website publication in this exercise were not verified.", "missingness": "Comparison of actual historical deployment events, the initial public-release time and a publication receipt for the current table are unverified.", "uncertainty": "The original metadata statements and event boundaries were linked. Actual historical deployment receipts and website publication in this exercise were not verified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original ID, canonical URL, initial-publication/server metadata and revision policy/history" } ], "reports": [ { "report_id": "S01", "title": "Didangelos et al. 2021. Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial", "url": "https://mdpi-res.com/d_attachment/nutrients/nutrients-13-00395/article_deploy/nutrients-13-00395.pdf", "report_type": "Decisive original trial", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "F01", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full article text in PDF", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S01-M1", "url": "https://mdpi-res.com/d_attachment/nutrients/nutrients-13-00395/article_deploy/nutrients-13-00395.pdf", "parent_url": "https://mdpi-res.com/d_attachment/nutrients/nutrients-13-00395/article_deploy/nutrients-13-00395.pdf" } ], "links": [ { "label": "Source", "url": "https://mdpi-res.com/d_attachment/nutrients/nutrients-13-00395/article_deploy/nutrients-13-00395.pdf" } ] }, { "report_id": "S02", "title": "Didangelos et al. — NLM bibliographic record", "url": "https://pubmed.ncbi.nlm.nih.gov/33513879/", "report_type": "Bibliographic record and abstract of the same original article", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "F01", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "PubMed bibliographic record and abstract", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S02-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/33513879/", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/33513879/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/33513879/" } ] }, { "report_id": "S03", "title": "ClinicalTrials.gov NCT04706377", "url": "https://clinicaltrials.gov/study/NCT04706377", "report_type": "Registration identity of the same original trial", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "F01", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full web clinical-trial registration record", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S03-M1", "url": "https://clinicaltrials.gov/study/NCT04706377", "parent_url": "https://clinicaltrials.gov/study/NCT04706377" } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT04706377" } ] }, { "report_id": "S04", "title": "Freynhagen et al. 2006. painDETECT: a new screening questionnaire to detect neuropathic components in patients with back pain", "url": "https://www.researchgate.net/publication/6771902_Freynhagen_R_Baron_R_Gockel_U_Tolle_TpainDETECT_a_new_screening_questionnaire_to_detect_neuropathic_components_in_patients_with_back_pain_Curr_Med_Res_Opin_22_1911-1920", "report_type": "Scale-definition report", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "MEASUREMENT_PAIND", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full original article text on the author's website", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S04-M1", "url": "https://www.researchgate.net/publication/6771902_Freynhagen_R_Baron_R_Gockel_U_Tolle_TpainDETECT_a_new_screening_questionnaire_to_detect_neuropathic_components_in_patients_with_back_pain_Curr_Med_Res_Opin_22_1911-1920", "parent_url": "https://www.researchgate.net/publication/6771902_Freynhagen_R_Baron_R_Gockel_U_Tolle_TpainDETECT_a_new_screening_questionnaire_to_detect_neuropathic_components_in_patients_with_back_pain_Curr_Med_Res_Opin_22_1911-1920" }, { "material_type": "Publisher's full article text in PDF", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S04-M2", "url": null, "parent_url": "https://www.researchgate.net/publication/6771902_Freynhagen_R_Baron_R_Gockel_U_Tolle_TpainDETECT_a_new_screening_questionnaire_to_detect_neuropathic_components_in_patients_with_back_pain_Curr_Med_Res_Opin_22_1911-1920" } ], "links": [ { "label": "Source", "url": "https://www.researchgate.net/publication/6771902_Freynhagen_R_Baron_R_Gockel_U_Tolle_TpainDETECT_a_new_screening_questionnaire_to_detect_neuropathic_components_in_patients_with_back_pain_Curr_Med_Res_Opin_22_1911-1920" } ] }, { "report_id": "S05", "title": "Yaqub, Siddique, Sulimani. 1992. Effects of methylcobalamin on diabetic neuropathy", "url": "https://pubmed.ncbi.nlm.nih.gov/1324807/", "report_type": "Adjacent methylcobalamin trial", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "F02", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "PubMed bibliographic record and abstract", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S05-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/1324807/", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/1324807/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/1324807/" } ] }, { "report_id": "S06", "title": "Mansour et al. 2026. Efficacy of Oral Vitamin B-12 at 1000 micrograms Compared with 2000 micrograms on Neuropathic Outcomes", "url": "https://pubmed.ncbi.nlm.nih.gov/41548600/", "report_type": "Adjacent oral-B12 active-dose trial", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "F03", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "PubMed bibliographic record and search-result title", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S06-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/41548600/", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/41548600/" }, { "material_type": "Publisher's full article text", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S06-M2", "url": "https://doi.org/10.1016/j.tjnut.2026.101368", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/41548600/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/41548600/" } ] }, { "report_id": "S07", "title": "MHRA. Metformin and reduced vitamin B12 levels: new advice for monitoring patients at risk", "url": "https://www.gov.uk/drug-safety-update/metformin-and-reduced-vitamin-b12-levels-new-advice-for-monitoring-patients-at-risk", "report_type": "Official safety notice", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "OFFICIAL_METFORMIN", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full official safety notice on the web", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S07-M1", "url": "https://www.gov.uk/drug-safety-update/metformin-and-reduced-vitamin-b12-levels-new-advice-for-monitoring-patients-at-risk", "parent_url": "https://www.gov.uk/drug-safety-update/metformin-and-reduced-vitamin-b12-levels-new-advice-for-monitoring-patients-at-risk" } ], "links": [ { "label": "Source", "url": "https://www.gov.uk/drug-safety-update/metformin-and-reduced-vitamin-b12-levels-new-advice-for-monitoring-patients-at-risk" } ] }, { "report_id": "S08", "title": "MHRA. Vitamin B12 (hydroxocobalamin, cyanocobalamin): cobalt sensitivity reactions", "url": "https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions", "report_type": "Official safety notice for other chemical forms", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "OFFICIAL_COBALT", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full official safety notice on the web", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S08-M1", "url": "https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions", "parent_url": "https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions" } ], "links": [ { "label": "Source", "url": "https://www.gov.uk/drug-safety-update/vitamin-b12-hydroxocobalamin-cyanocobalamin-advise-patients-with-known-cobalt-allergy-to-be-vigilant-for-sensitivity-reactions" } ] }, { "report_id": "S09", "title": "NIH ODS. Vitamin B12: Fact Sheet for Health Professionals — supplied record 110 citation", "url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/", "report_type": "Prior excerpt from an official fact sheet", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "ODS_REUSED110", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full fact sheet on the web", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S09-M1", "url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/", "parent_url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/" }, { "material_type": "Excerpted citation from the stored summary of prior record 110", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S09-M2", "url": null, "parent_url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/" } ], "links": [ { "label": "Source", "url": "https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/" } ] }, { "report_id": "S10", "title": "UNI-PHARMA. B12 fix product and food-supplement catalogue", "url": "https://www.uni-pharma.gr/en/nonprescriptive/b12-fix/", "report_type": "Manufacturer's product description", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "MANUFACTURER_B12FIX", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full manufacturer's product description on the web", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S10-M1", "url": "https://www.uni-pharma.gr/en/nonprescriptive/b12-fix/", "parent_url": "https://www.uni-pharma.gr/en/nonprescriptive/b12-fix/" }, { "material_type": "Manufacturer's food-supplement catalogue (file format unverified)", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S10-M2", "url": null, "parent_url": "https://www.uni-pharma.gr/en/nonprescriptive/b12-fix/" } ], "links": [ { "label": "Source", "url": "https://www.uni-pharma.gr/en/nonprescriptive/b12-fix/" } ] }, { "report_id": "S11", "title": "Jayabalan et al. 2016. Vitamin B supplementation for diabetic peripheral neuropathy", "url": "https://www.smj.org.sg/article/vitamin-b-supplementation-diabetic-peripheral-neuropathy", "report_type": "Discovery identity of a related review", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "REVIEW2016", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full review article text", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S11-M1", "url": "https://www.smj.org.sg/article/vitamin-b-supplementation-diabetic-peripheral-neuropathy", "parent_url": "https://www.smj.org.sg/article/vitamin-b-supplementation-diabetic-peripheral-neuropathy" } ], "links": [ { "label": "Source", "url": "https://www.smj.org.sg/article/vitamin-b-supplementation-diabetic-peripheral-neuropathy" } ] }, { "report_id": "S12", "title": "Mandra et al. 2026. Vitamin B Supplementation for Diabetic Peripheral Neuropathy: A Review and Meta-Analysis", "url": "https://www.mdpi.com/2077-0383/15/13/5156", "report_type": "Discovery identity of a mixed-B-vitamin meta-analysis", "existence": "Retained citation identity and historical access/verification locations checked", "acquired_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", "study_family": "REVIEW2026", "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.", "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full review article text", "public_status": "Unverified (only retained historical access is linked; no lookup in this exercise)", "access_status": "Not attempted in this exercise", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The existence of a link/bibliographic record is separate from actual acquisition, reading and suitability for the selected question.", "material_id": "S12-M1", "url": "https://www.mdpi.com/2077-0383/15/13/5156", "parent_url": "https://www.mdpi.com/2077-0383/15/13/5156" } ], "links": [ { "label": "Source", "url": "https://www.mdpi.com/2077-0383/15/13/5156" } ] } ], "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility criteria and reasons for changes, and distinguish variations in the intervention.", "review_level": "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." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish and link studies and reports, and do not omit a study solely because its outcomes are not reported.", "review_level": "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." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting.", "review_level": "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." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "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." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Questions about harms may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence.", "review_level": "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." } ], "status_dictionary": { "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." }, "study_overlap": { "state": "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.", "unique_trial_count": null, "unique_participant_count": null, "reason": "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." }, "history": [ { "date": "2026-11-05", "kind": "Separation of public-facing display and data", "view_version": "1.0", "change": "The public-facing display and data were prepared from the existing 43 items. No new clinical search, change to verification statuses or scoring was performed." } ], "language": "en", "translation_date": "2026-11-05" }