{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3122-main", "verdict_number": "3122", "title": "Ordinary thiamine (vitamin B1), hydrochloride × Eight-week salbutamol-responsive digital reflective-index response", "view_version": "1.0", "view_created_date": "2026-11-07", "criteria_version": "v3122-ORAL-THIAMINE-RI-1.1", "criteria_date": "2026-10-04", "review_date": "2026-10-04", "legacy_evidence_date": "2026-09-16", "review_scope": { "materials_read": "Summary of the selected question in the retained manuscript and records of case-specific criteria and their application", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "Reading stored summaries is distinguished from not reading external source materials or historical separate documents, while preserving the original verdict, numerical values and unverified information. No new clinical search, source reading, effect calculation or reassessment was 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 at high cardiovascular risk; actual mean age 61 years; baseline deficiency and numerically established endothelial dysfunction unverified", "intervention": "Thiamine hydrochloride tablets with a single active ingredient according to the registration; actual product batch and excipients unverified · Oral", "dose": "Reported oral thiamine hydrochloride 300 mg/day; free-thiamine equivalent and actual 1-time dosing schedule unverified", "comparator": "Crossover placebo in the same participants; background diabetes and cardiovascular medications are described, but their exact balance between periods is unverified", "endpoint": "Digital photoplethysmographic reflective-index response after inhaled salbutamol at the end of the 8-week treatment period; not brachial artery FMD", "duration": "Each treatment period 8 weeks; washout between periods 2 weeks", "excluded_extensions": "Transferring positive or negative results from other thiamine preparations, intravenous use, dietary exposure or combination products / Automatically extending to FMD, prevention of cardiovascular events or cleansing blood vessels / Presenting nonsignificance as proof of an effect of 0, equivalence or exclusion of important benefit / Counting the thesis, poster, registration and mirror as independent replications / Transferring product-information cautions for other products/intravenous use to the actual trial's oral event incidence / New grades/scores, optimal doses, personal dosing instructions or instructions to change existing treatment" }, "requirements": [ { "item_id": "N01", "question_type": "Independent claim", "question": "Which population, regimen and 8-week functional response does the independent table address?", "needed": "Original locations of the current claim, PICOT, surrogate measure and excluded questions", "role": "Required", "role_reason": "Needed to distinguish the entire ordinary-thiamine page from the selected functional outcome.", "application_exception": "Preserve the original claim exactly as recorded at /ko/effect, without automatically creating new efficacy subclaims for FMD, clinical events or TDP.", "criterion": "Link the selected population, actual comparison, regimen and timing to the original identity of digital RI.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed; M03 §3.2.1; detailed population criteria are self-designed; M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are self-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed — Case-specific adaptation for Independent claim. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "In subsequent research, first fix the population, oral regimen, placebo and RI measurement time, and distinguish other outcomes alongside them.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The original claim is “8-week salbutamol-induced finger reflective-index response.” It addresses the RI response between oral thiamine hydrochloride and crossover placebo in the same adults with type 2 diabetes at high cardiovascular risk.", "condition_status": "Met", "status_reason": "The exact current original claim has been linked to the boundary of the actual direct trial result. This Met status does not establish benefit.", "missingness": "Original RI units, variance, denominator, adjusted effect and related gaps remain in separate rows.", "uncertainty": "Verifying the identity of this table's question differs from clinical certification of FMD or event prevention.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original locations of the current claim, PICOT, surrogate measure and excluded questions" }, { "item_id": "N02", "question_type": "Molecule and actual product", "question": "Have the single registered active ingredient and the actual product batch been distinguished?", "needed": "Actual trial product ingredient list, batch, excipients and manufacturing-origin information", "role": "Required", "role_reason": "Because active-ingredient identity and the actual formulation/batch do not have the same level of verification.", "application_exception": "Do not substitute Flamingo product information from a different era for registered Tyvera, or automatically equate it with benfotiamine or combination products.", "criterion": "Record ordinary thiamine hydrochloride and the registered product identity separately from the unverified actual batch/excipients.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are self-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; own application — Case-specific adaptation for Molecule and actual product. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Propose a replication procedure that obtains product analyses and batch records and verifies actual administration of the single active ingredient.", "current_reports": [ "S01", "S03", "S16" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The regimen is oral ordinary thiamine hydrochloride, and the registered product is Tyvera 100 mg tablets with a single active ingredient. The actual batch, excipients and manufacturing origin are unverified. The official S16 product is not the same trial batch.", "condition_status": "Partly verified", "status_reason": "The active ingredient/registered product is retained, but detailed information on the actual trial product remains to be verified.", "missingness": "Actual manufacturing, batch, excipients and purity/release form unverified.", "uncertainty": "Ingredient lists and safety wording for different products cannot be transferred as facts about the current trial product.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Actual trial product ingredient list, batch, excipients and manufacturing-origin information" }, { "item_id": "N03", "question_type": "Nominal amount and active amount", "question": "Have the reported 300 mg/day and the free-thiamine equivalent been distinguished?", "needed": "Actual dose records, product content/units, 1-time dosing schedule and amount actually taken", "role": "Required", "role_reason": "Needed to avoid converting the nominal total hydrochloride amount into the active contribution or an optimal personal dose.", "application_exception": "Do not newly calculate the actual number of tablets taken per administration or the dosing schedule from the 100 mg tablets and 300 mg/day.", "criterion": "Preserve the reported daily total and mark the free-thiamine conversion and actual 1-time schedule as unverified.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are self-designed; M03 §3.2.1–3.2.4; details on dose, persistence and effect modification are self-designed — Case-specific adaptation for Nominal amount and active amount. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "After verifying actual administration records and content units, address any necessary dose comparison under a separate protocol.", "current_reports": [ "S01", "S03" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The reported total oral thiamine hydrochloride amount is 300 mg/day. The free-thiamine equivalent and actual 1-time dosing schedule are unverified. Do not determine a personal dose from the registered Tyvera 100 mg product label.", "condition_status": "Partly verified", "status_reason": "The reported total is within the verified scope, but conversion to the active amount and the actual schedule remain unresolved.", "missingness": "Hydrochloride/free-thiamine conversion and actual amount taken 1 time/frequency unverified.", "uncertainty": "The study total is not a personal dosing instruction or evidence of an optimal dose.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Actual dose records, product content/units, 1-time dosing schedule and amount actually taken" }, { "item_id": "N04", "question_type": "Treatment and washout periods", "question": "Have each 8-week treatment period and the 2-week washout been linked to the outcome time?", "needed": "Information on administration and visit schedules by period and RI measurement times", "role": "Required", "role_reason": "Needed to avoid confusing the crossover trial's two treatment periods, washout and original outcome time as the same total duration.", "application_exception": "Do not turn the discrepancy in registered calendar completion dates into a conflict over the reported treatment duration of 8 weeks.", "criterion": "Link each 8-week period, the 2-week washout and RI at the end of treatment to their original locations.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are self-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed; M03 §3.2.1–3.2.4; details on dose, persistence and effect modification are self-designed — Case-specific adaptation for Treatment and washout periods. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Check implementation of each treatment and washout against visit/exposure records, and plan long-term persistence questions under separate follow-up.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "Each reported treatment period is 8 weeks, with a 2-week washout between periods. RI is limited to the salbutamol response at the end of the 8-week treatment period. Leave the difference in calendar completion dates in a separate registry-metadata row.", "condition_status": "Met", "status_reason": "The retained nominal treatment/washout periods and selected time point have been accurately linked.", "missingness": "Actual visit dates, complete exposure in each period and long-term persistence data are unverified.", "uncertainty": "A Met status for duration reporting does not establish that washout excluded carryover or that long-term efficacy criteria were met.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Information on administration and visit schedules by period and RI measurement times" }, { "item_id": "N05", "question_type": "Actual population and selection", "question": "Have the actual high-risk adults with type 2 diabetes and the registered eligibility plan been distinguished?", "needed": "Baseline characteristics by group/sequence, actual inclusion/exclusion flow and definitions of risk and endothelial function", "role": "Required", "role_reason": "Needed to avoid promoting planned registered selection criteria into actual characteristics of all participants or baseline endothelial dysfunction.", "application_exception": "Verify the target scope from registered eligibility/the institutional abstract, without inferring detailed diagnoses or the population mix for all participants.", "criterion": "Distinguish the actual high-risk adult population with type 2 diabetes and mean age from the remaining baseline-data gaps.", "basis": "M03 §3.2.1; detailed population criteria are self-designed; M08 §8.1–8.2.3; own application — Case-specific adaptation for Actual population and selection. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "In subsequent comparisons, prespecify risk selection and baseline vascular function and disclose actual participant characteristics.", "current_reports": [ "S01", "S02", "S03" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The actual population consists of adults with type 2 diabetes at high cardiovascular risk, with a retained mean age of 61 years. Numerically established baseline endothelial dysfunction, individual inclusion/exclusion and characteristics by sequence are unverified.", "condition_status": "Partly verified", "status_reason": "The basic identity of the actual population is available, but detailed baseline characteristics and representativeness remain to be verified.", "missingness": "Baseline characteristics by sequence, actual fulfillment of eligibility in all participants and numerically established endothelial dysfunction unverified.", "uncertainty": "The registration plan does not replace actual composition data and does not automatically extend to all adults with diabetes.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Baseline characteristics by group/sequence, actual inclusion/exclusion flow and definitions of risk and endothelial function" }, { "item_id": "N06", "question_type": "Baseline nutritional status", "question": "Can baseline thiamine deficiency and the conditions for additional supplementation be established?", "needed": "Baseline thiamine/TDP, deficiency thresholds, dietary/supplement intake and prespecified stratification data", "role": "Required (nutritional applicability)", "role_reason": "Needed to distinguish possible correction of deficiency from the effect of additional supplementation in a population of unknown status.", "application_exception": "Do not use the thesis abstract's general discussion of deficiency as an actual measurement of deficiency in participants.", "criterion": "Retain the actual level of verification of baseline status, deficiency criteria and total intake.", "basis": "M03 §3.2.1; detailed population criteria are self-designed; M03 §3.2.1–3.2.4; details on dose, persistence and effect modification are self-designed — Case-specific adaptation for Baseline nutritional status. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Measure baseline status and assess effect modification by deficiency status in a separately planned, prespecified analysis.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "Baseline thiamine deficiency is unverified. The general introduction to deficiency in the S01 abstract is not an actual measurement of this population's baseline status, and an increase in blood TDP does not establish baseline deficiency either.", "condition_status": "Unverified", "status_reason": "Actual deficiency classification and intake data for participants in the direct trial cannot be established from the retained inputs.", "missingness": "Baseline deficiency/nondeficiency, thresholds, total intake and nutritional subgroups unverified.", "uncertainty": "This gap does not mean that all participants were deficient or all were sufficient, or that there was no effect.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Baseline thiamine/TDP, deficiency thresholds, dietary/supplement intake and prespecified stratification data" }, { "item_id": "N07", "question_type": "Crossover placebo and background treatment", "question": "Have the placebo comparison and background-medication balance between periods been distinguished?", "needed": "Information on medications, rescue treatment, disease status/changes and their handling for the effect of interest by period", "role": "Required", "role_reason": "Because changes in background diabetes/cardiovascular treatment may be mixed with the contribution of thiamine.", "application_exception": "Even in a crossover comparison in the same participants, do not assume that all medication and disease changes were identical between periods.", "criterion": "Distinguish the actual placebo comparison from gaps in period-specific concomitant/rescue treatment and the handling of changes.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are self-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; own application — Case-specific adaptation for Crossover placebo and background treatment. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Propose a comparison that records common treatment and prespecifies how period-specific changes and rescue treatment will be handled in analysis.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The actual comparison is crossover placebo in the same participants, with background diabetes/cardiovascular medications described. Exact medication balance, changes and handling of rescue treatment by period are unverified.", "condition_status": "Partly verified", "status_reason": "The placebo comparison is identified, but actual differences in concomitant treatment between periods and their handling have not been verified.", "missingness": "Actual period-specific distributions of concomitant medications, disease changes and rescue treatment, and their effects on analysis, unverified.", "uncertainty": "The crossover design itself is not evidence that it removed changes in concomitant treatment/disease over time.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Information on medications, rescue treatment, disease status/changes and their handling for the effect of interest by period" }, { "item_id": "N08", "question_type": "Conflicting design labels", "question": "Have the actual crossover design and the registry's parallel/crossover checkboxes been distinguished?", "needed": "Full protocol, registry amendment history, actual allocation sequences and design explanation", "role": "Required", "role_reason": "Needed to avoid hiding the conflicting registry labels or arbitrarily changing the actually reported design to a parallel trial.", "application_exception": "Do not reassess conflicting registry checkboxes as errors in all RI numbers or as absence of random allocation.", "criterion": "Preserve the actual crossover report and the registry's Yes entries for both designs at their respective original locations.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is self-designed; M08 §8.1–8.2.3; own application; M08 Table 8.2.a, M04 §4.6.3; own application — Case-specific adaptation for Conflicting design labels. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Compare the original protocol and amendment history to verify why both boxes were checked, and reconcile the design actually implemented with its reporting.", "current_reports": [ "S01", "S02", "S03" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "S01/S02 report a randomized, double-blind crossover pilot trial. S03 records Yes for both the parallel and crossover checkboxes. Retain the actual crossover report and leave the checkbox discrepancy unresolved.", "condition_status": "Conflicting information", "status_reason": "The discrepancy in simultaneous design checkmarks within the same registration is retained. Do not change the actual treatment comparison into a new parallel design.", "missingness": "Protocol/SAP, reasons for registry amendments and original explanation of the checkmarks unverified.", "uncertainty": "The conflict in this row is limited to the registered design labels; it does not establish a conflict across all treatment effects or causal invalidity.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Full protocol, registry amendment history, actual allocation sequences and design explanation" }, { "item_id": "N09", "question_type": "Sequence generation and concealment", "question": "Have random sequence generation and allocation concealment been verified?", "needed": "Information on sequence generation, allocation concealment and actual baseline balance by sequence", "role": "Required (causal efficacy)", "role_reason": "Because the labels randomized and double-blind alone do not establish that allocation issues were resolved.", "application_exception": "The crossover/pilot label does not establish detailed generation, concealment or baseline balance, or completion of a formal RoB assessment.", "criterion": "Record the allocation label and the verified scope of actual sequence generation, concealment and balance.", "basis": "M08 §8.1–8.2.3; own application — Case-specific adaptation for Sequence generation and concealment. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Propose a comparison that prespecifies sequence-generation and concealment procedures and baseline balance and discloses their actual implementation.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "There is a report of a randomized, double-blind crossover pilot trial, but detailed procedures for sequence generation and allocation concealment are unverified. Do not state that a formal bias tool was applied.", "condition_status": "Partly verified", "status_reason": "The design label is available, but the necessary allocation details are not retained.", "missingness": "Generation algorithm, concealment procedures, allocation implementation and baseline balance unverified.", "uncertainty": "Unverified details differ from proof of a flaw or certification of no bias.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Information on sequence generation, allocation concealment and actual baseline balance by sequence" }, { "item_id": "N10", "question_type": "Completion, allocation and analysis denominators", "question": "Have the 34 completers been distinguished from the randomized count and number of analyzed RI pairs?", "needed": "CONSORT/crossover flow, allocation/completion/measurement by sequence and number of paired RI analyses", "role": "Required", "role_reason": "Needed to avoid counting the same person's two periods as independent people or turning completers into a confirmed analysis denominator.", "application_exception": "Do not add up the 34 unique completers as 68 people; keep the randomized count, denominators by sequence and number of analyzed RI pairs unverified.", "criterion": "Link completion, allocation, sequence, measurement and analysis to the denominator at each stage.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each design are self-designed; M08 §8.2.2, M15 §15.3.1; own application — Case-specific adaptation for Completion, allocation and analysis denominators. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Propose reporting participant flow and paired denominators for each endpoint, with differences between allocation, completion and analysis disclosed.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The 34 unique completers are retained. The randomized count, denominators by sequence and number of analyzed RI pairs are separately unverified. Do not count the two periods as 68 independent participants.", "condition_status": "Partly verified", "status_reason": "Only the completion stage is established; analysis denominators and the boundaries of attrition require further verification.", "missingness": "Allocated count, number of people by sequence, paired RI denominator and exclusion flow unverified.", "uncertainty": "The 34 completers cannot be used as n for every outcome or as the number in a complete paired analysis.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "CONSORT/crossover flow, allocation/completion/measurement by sequence and number of paired RI analyses" }, { "item_id": "N11", "question_type": "Missing data and analysis populations", "question": "Can the handling of attrition/missing data and the ITT/PP analysis populations be established?", "needed": "Data on allocation/attrition, reasons for missingness, definitions of analysis populations and sensitivity analyses", "role": "Required", "role_reason": "Needed to avoid automatically concluding from the completer count that only completers were analyzed.", "application_exception": "Do not arbitrarily label the completer report as complete-case, ITT or PP, or describe the information as unreported throughout the unread full text.", "criterion": "Link the verified scope of the actual analysis population, missing-data handling and attrition by sequence to the effect of interest.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each design are self-designed; M08 §8.2.2, M15 §15.3.1; own application — Case-specific adaptation for Missing data and analysis populations. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Prespecify the effect of interest and analysis population, and plan sensitivity analyses that account for missing crossover data.", "current_reports": [ "S01", "S02", "S06", "S07" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "Apart from the 34 completers, the actual RI analysis population and reasons for and handling of attrition/missingness are unverified. Do not assert that this was a completer analysis.", "condition_status": "Unverified", "status_reason": "Losses after allocation and the analysis definition cannot be established from the retained inputs read.", "missingness": "ITT/PP, missing paired data, reasons for attrition and handling of exclusions/imputation unverified.", "uncertainty": "An information gap does not establish absence of missing data or the actual magnitude of bias.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Data on allocation/attrition, reasons for missingness, definitions of analysis populations and sensitivity analyses" }, { "item_id": "N12", "question_type": "Washout and carryover", "question": "Can it be established whether the 2-week washout excluded carryover?", "needed": "Crossover protocol, baseline/exposure by period and information on carryover assessment and handling", "role": "Required (crossover trial)", "role_reason": "Because residual effects of the previous treatment may be mixed with RI in the next period.", "application_exception": "Do not conclude from the nominal 2-week washout alone that there was no carryover or that washout was sufficient.", "criterion": "Distinguish the washout report from direct information on carryover assessment/handling and restoration of baseline in each period.", "basis": "M08 §8.1–8.2.3; own application; M08 §8.2.2, M15 §15.3.1; own application — Case-specific adaptation for Washout and carryover. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Prespecify the rationale for washout and baseline measurements by period, and plan a crossover analysis that examines residual/carryover effects.", "current_reports": [ "S01", "S02", "S06" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "A 2-week washout is reported, but data on carryover and period-specific recovery/handling are unverified. Do not use the existence of washout as evidence that carryover was excluded.", "condition_status": "Unverified", "status_reason": "Information needed to verify actual residual/carryover effects on the selected RI comparison remains outstanding.", "missingness": "Rationale for washout, baseline recovery, carryover estimation/handling and residual exposure unverified.", "uncertainty": "Do not conclude from the carryover gap that carryover actually occurred or that the crossover trial is invalid.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Crossover protocol, baseline/exposure by period and information on carryover assessment and handling" }, { "item_id": "N13", "question_type": "Sequence and period effects", "question": "Were sequence and period effects handled in the actual RI analysis?", "needed": "RI, baseline/medications, interactions and analysis model by sequence/period", "role": "Required (crossover trial)", "role_reason": "Because calendar time/period and allocation sequence can affect treatment differences even in before-and-after observations of the same person.", "application_exception": "Do not state that sequence and period effects were automatically removed because the participants were the same.", "criterion": "Link sequence/period-specific data to the model's effect of interest and its handling.", "basis": "M08 §8.1–8.2.3; own application; M08 §8.2.2, M15 §15.3.1; own application — Case-specific adaptation for Sequence and period effects. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Prespecify the treatment, period and sequence terms of interest and disclose sequence-specific data and sensitivity analyses.", "current_reports": [ "S01", "S02", "S06" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "Sequence and period effects and the handling of the corresponding model terms are unverified. Preserve the actual crossover design, without claiming that time/sequence effects were removed.", "condition_status": "Unverified", "status_reason": "The currently retained methods do not contain the actual sequence/period model or its results.", "missingness": "Tables by sequence, period terms, changes by period and handling of interactions/modeling unverified.", "uncertainty": "Unverified information does not establish the actual magnitude of period effects or how much they are mixed with treatment effects.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "RI, baseline/medications, interactions and analysis model by sequence/period" }, { "item_id": "N14", "question_type": "Paired effect of interest", "question": "Can the adjusted paired RI effect and the actual choice of test be established?", "needed": "RI analysis plan, paired source data/covariance, adjusted model, test type and effect estimator", "role": "Required", "role_reason": "Because a descriptive difference between two summary values differs from the actual paired causal estimate and test statistic.", "application_exception": "Do not back-calculate the outcome-specific ANOVA/Friedman choice, covariance or degrees of freedom from P=.63.", "criterion": "Retain the verified scope of the effect of interest, analysis population, pairing/covariance and actual test definition.", "basis": "M08 §8.2.2, M15 §15.3.1; own application; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed — Case-specific adaptation for Paired effect of interest. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Propose an analysis that prespecifies the paired effect of interest and period/sequence adjustment and reports that effect and its interval.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "RI is a crossover comparison in the same participants. The exact adjusted paired effect, covariance and number of analyzed pairs are unverified, and the RI-specific ANOVA/Friedman choice has not been verified either.", "condition_status": "Unverified", "status_reason": "A comparison P value is reported, but the actual estimation/test definition cannot be established.", "missingness": "Paired covariance, effect model, test type, degrees of freedom and effect of interest unverified.", "uncertainty": "Do not create new SE/CI or causal effects using an independent two-group formula or back-calculation from the P value.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "RI analysis plan, paired source data/covariance, adjusted model, test type and effect estimator" }, { "item_id": "N15", "question_type": "RI measurement procedure", "question": "Have salbutamol RI measurement timing, sign convention and assessor blinding been verified?", "needed": "Measurement protocol, challenge dose/time afterward, sign convention, baseline RI and operator-blinding/quality information", "role": "Required", "role_reason": "Because post-challenge timing, sign convention and assessment conditions may change interpretation even when the measure has the same name.", "application_exception": "Do not arbitrarily fill in operator blinding, challenge dose/timing or directional sign convention from the double-blind label.", "criterion": "Record the actual digital photoplethysmography/inhalation-challenge method and the remaining measurement dimensions.", "basis": "M08 Table 8.2.a, M03 §3.2.4; own application; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed — Case-specific adaptation for RI measurement procedure. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Propose a method that standardizes the RI challenge, collection time, sign convention and assessor blinding and reports baseline/reproducibility data.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The response is digital photoplethysmographic RI after inhaled salbutamol at the end of 8 weeks. Exact post-challenge timing, directional sign convention, baseline RI and operator blinding are unverified.", "condition_status": "Partly verified", "status_reason": "The type of physiological function test is verified, but measurement details and the dimensions needed to interpret a favorable direction remain unresolved.", "missingness": "Salbutamol challenge details, timing after measurement, sign convention, baseline RI and operator blinding unverified.", "uncertainty": "The sign of −1.5 alone cannot establish whether vascular function improved or worsened.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Measurement protocol, challenge dose/time afterward, sign convention, baseline RI and operator-blinding/quality information" }, { "item_id": "N16", "question_type": "Surrogate measure and clinical boundary", "question": "Has digital RI been distinguished from FMD and prevention of clinical events?", "needed": "Measurement definition and separate direct results for claims about event prevention/quality of life", "role": "Required (claim boundary); separate evidence for extension to events", "role_reason": "Needed to avoid automatically translating the selected functional response into other vascular measures or long-term events.", "application_exception": "Do not mechanically require cardiovascular-event trials merely to preserve observations for the RI question itself; extension to event prevention remains separately unverified.", "criterion": "Identify the distinct questions concerning RI, brachial artery FMD, VCAM-1, TDP and clinical events.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed; M03 §3.2.4; own boundaries on extrapolation — Case-specific adaptation for Surrogate measure and clinical boundary. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "If a clinical-event question is requested, address it through a study with a separate protocol, follow-up and event adjudication.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The current endpoint is salbutamol-responsive digital RI, not brachial artery FMD or prevention of myocardial infarction/stroke. Preserve the original boundary that an actual functional alternative was selected because no directly eligible FMD result was verified in this search.", "condition_status": "Met", "status_reason": "The manuscript's boundaries for selected and excluded endpoints have been accurately linked, without establishing clinical-event benefit.", "missingness": "Long-term clinical-event, quality-of-life and direct FMD data have not been acquired as answers to the current question.", "uncertainty": "Nonsignificance of the RI result neither refutes nor establishes FMD or event prevention.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Measurement definition and separate direct results for claims about event prevention/quality of life" }, { "item_id": "N17", "question_type": "Reported RI values and P", "question": "Have the two reported RI values and P=0.63 been attributed to the original time point?", "needed": "P72 RI result sentence, original table/units, explanation of variance and analysis location", "role": "Required", "role_reason": "Needed to avoid deleting favorable or nonsignificant results or transferring them as values for another functional endpoint.", "application_exception": "Do not arbitrarily assign the type of ± value, absolute change or percentage to 5.3±9.2/6.8±6.9.", "criterion": "Retain the reported values, 8-week RI and original P together with the gaps in units/variance.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is self-designed — Case-specific adaptation for Reported RI values and P. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Check the original results table to compare definitions of summary statistics, and specify units, variance and effect estimates in subsequent reporting.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The 8-week RI is reported as thiamine 5.3 ± 9.2, placebo 6.8 ± 6.9, P=0.63. These values are the reported statistics for that salbutamol RI response; units and variance type are unverified.", "condition_status": "Partly verified", "status_reason": "The original numbers/P for the direct comparison are retained, but the units and variance of the summary statistics and the analysis definition remain unresolved.", "missingness": "Original units, SD/SE, baseline/change definition and adjusted-analysis details unverified.", "uncertainty": "Retain the nonsignificant values without converting them into an effect of 0, equivalence or FMD numbers.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "P72 RI result sentence, original table/units, explanation of variance and analysis location" }, { "item_id": "N18", "question_type": "Units and variance type", "question": "Have the original RI units and whether the ± values are SD or SE been verified?", "needed": "RI units, explanation of summary statistics, SD/SE, paired covariance and denominator data", "role": "Required", "role_reason": "Needed to avoid creating a CI, percentage points or causal estimate from ± values of unknown type.", "application_exception": "Do not supplement a report lacking units with FMD %, absolute percentage points or relative percentage change.", "criterion": "Clearly retain the absence of an original location providing the units/variance type.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each design are self-designed; M15 §15.3.1–15.3.3; own application — Case-specific adaptation for Units and variance type. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Propose reporting the RI units, variance type and number of analyzed pairs explicitly, with intervals appropriate to the paired structure.", "current_reports": [ "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The original units of the two RI values and whether ±9.2/±6.9 denote SD or SE are unverified. Absolute percentage points, relative percentage change and FMD % are not verified values.", "condition_status": "Unverified", "status_reason": "Although direct numbers are available, the current inputs contain no original explanation establishing their units or variance type.", "missingness": "Original RI units, SD/SE/other variance measure and paired covariance unverified.", "uncertainty": "This gap in the available information is not a new judgment that the reported numbers are erroneous and does not authorize interval recalculation.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "RI units, explanation of summary statistics, SD/SE, paired covariance and denominator data" }, { "item_id": "N19", "question_type": "Historical descriptive difference", "question": "Has the existing difference of −1.5 been distinguished from an adjusted paired causal estimate?", "needed": "Source location of the existing calculation, effect of interest and actual adjusted paired-estimate data", "role": "Required", "role_reason": "Because a simple difference between two reported values is not guaranteed to equal the actual crossover trial's effect of interest.", "application_exception": "Only cite the existing calculation record; perform no new arithmetic, paired CI/SE calculation or FMD conversion in this work.", "criterion": "Record the historical calculation location for −1.5 together with its descriptive nature and unit limitations.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed; M08 §8.2.2, M15 §15.3.1; own application; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is self-designed — Case-specific adaptation for Historical descriptive difference. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "If the original analysis is acquired, report the descriptive summary difference separately from the prespecified paired effect of interest.", "current_reports": [ "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The descriptive difference of −1.5 between thiamine and placebo is a retained existing calculation record. Its original unit is unverified; it is not an adjusted paired causal estimate or FMD percentage points. It was not calculated in this work.", "condition_status": "Met", "status_reason": "The identity and interpretive limitations of the existing descriptive value have been accurately preserved.", "missingness": "The exact adjusted estimator, SE/df/CI and paired covariance are separately unverified.", "uncertainty": "A Met status for preserving the descriptive value does not establish a causal treatment effect or the direction of benefit.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Source location of the existing calculation, effect of interest and actual adjusted paired-estimate data" }, { "item_id": "N20", "question_type": "Nonsignificance and equivalence", "question": "Has P=0.63 been distinguished from a benefit of 0, equivalence or exclusion of important benefit?", "needed": "Direct RI effect interval, justified importance/equivalence criteria and testing plan", "role": "Required", "role_reason": "Because a nonsignificant comparison in a small pilot trial alone cannot establish an exactly null effect or equivalence.", "application_exception": "Retain the original nonsignificant result; do not back-calculate effect direction or magnitude without a CI or override it with positive results for other preparations.", "criterion": "Identify the significance information provided by P and the different evidence required to judge no effect, equivalence and importance.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is self-designed; M15 §15.3.1–15.3.3; own application — Case-specific adaptation for Nonsignificance and equivalence. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "If equivalence or exclusion of important benefit is the question, plan separate verification with prespecified criteria, an effect of interest and adequate precision.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The reported comparison P=0.63 is nonsignificant. It does not establish absence of important benefit or prove an effect of exactly 0 or equivalence. Conversely, an increase in TDP or results for other preparations do not establish this RI efficacy either.", "condition_status": "Met", "status_reason": "The original result has been retained, together with the boundary between nonsignificance and separate clinical/equivalence conclusions.", "missingness": "CI, MCID, prespecified equivalence margin and the corresponding test are unverified.", "uncertainty": "The magnitude of possible remaining benefit or of effects excluded cannot be established.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Direct RI effect interval, justified importance/equivalence criteria and testing plan" }, { "item_id": "N21", "question_type": "Intervals and clinical importance", "question": "Can the direct RI CI and an important difference be established?", "needed": "RI effect/CI, confidence level, variance, denominator and validated criteria for clinical importance", "role": "Required", "role_reason": "Because precision/clinical importance cannot be determined from the number of completers or trial families alone.", "application_exception": "Do not adopt a common minimum participant count, duration or arbitrary MCID; retain unverified intervals/criteria.", "criterion": "Explain the relationship between the interval for the actual effect of interest and justified evidence of importance, or why interpretation is not possible.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each design are self-designed; M15 §15.3.1–15.3.3; own application — Case-specific adaptation for Intervals and clinical importance. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "First define the RI effect of interest and the basis for importance, then design the required precision to match that basis.", "current_reports": [ "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The RI confidence interval, confidence level and MCID are unverified. The 34 completers and P=0.63 alone do not establish exclusion of important benefit or its remaining magnitude.", "condition_status": "Unverified", "status_reason": "The direct effect interval and basis for clinical importance are currently unavailable, so interpretation of magnitude cannot be completed.", "missingness": "CI for the effect of interest, confidence level and MCID/validity evidence unverified.", "uncertainty": "The current CX is the historical handling in the original verdict; this row assigns no new grade or precision score.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "RI effect/CI, confidence level, variance, denominator and validated criteria for clinical importance" }, { "item_id": "N22", "question_type": "Registered endpoints and reporting", "question": "Have the registered primary (1st) VCAM-1 endpoint and the prespecified rank/analysis of RI been distinguished?", "needed": "Full registration/protocol, SAP, prespecified RI rank and multiple-comparison/amendment history", "role": "Required", "role_reason": "Needed to avoid promoting the page's functional endpoint to the registered primary (1st) endpoint or to a significant secondary (2nd) success.", "application_exception": "Do not change the registered primary (1st) endpoint or use the unverified prespecified RI rank/SAP as proof of selective reporting.", "criterion": "Indicate the extent of comparison between registered endpoints and the original RI report, and reasons for multiple comparisons/changes.", "basis": "M08 Table 8.2.a, M04 §4.6.3; own application; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed — Case-specific adaptation for Registered endpoints and reporting. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Propose subsequent reporting that prespecifies the RI of interest, time point and model and discloses reasons for changes and all endpoints.", "current_reports": [ "S02", "S03", "S06", "S07" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The registered primary (1st) endpoint is VCAM-1. Do not promote the page's 8-week RI to the registered primary (1st) endpoint; RI's prespecified rank, analysis plan and handling of multiple comparisons are unverified. No significant secondary (2nd) success is claimed.", "condition_status": "Partly verified", "status_reason": "The registered primary (1st) endpoint can be distinguished from the reported RI, but a complete comparison of prespecified analyses and rankings remains outstanding.", "missingness": "Full protocol/SAP, RI rank, multiple comparisons and reasons for changes unverified.", "uncertainty": "A verification gap is neither proof of selective reporting nor certification of its absence.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Full registration/protocol, SAP, prespecified RI rank and multiple-comparison/amendment history" }, { "item_id": "N23", "question_type": "Planned schedule and actual administration", "question": "Have the registered schedule of 1 time per 1 day and the actual daily total/meal timing been distinguished?", "needed": "Actual administration times/frequency, meal conditions, dosing diaries and plan-change information", "role": "Required", "role_reason": "Because a planned schedule does not guarantee actual administration frequency, meal conditions or adherence implementation.", "application_exception": "Do not confirm the HRA plan's once daily as the actual 1-time schedule or adopt overnight fasting from the S18 mirror as an original-trial fact.", "criterion": "Separate the verification levels of the reported total, registered plan and actual schedule/meal conditions.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are self-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; own application; M08 Table 8.2.a, M04 §4.6.3; own application — Case-specific adaptation for Planned schedule and actual administration. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Record actual administration and meal conditions and prespecify how changes/deviations from the plan will be handled.", "current_reports": [ "S01", "S03", "S05", "S18" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The registration/ethics plan is 1 time per 1 day, while the actual report gives a daily total. The actual 1-time dosing schedule and meal timing are unverified. Do not adopt overnight fasting from the S18 mirror as a fact verified in the source materials.", "condition_status": "Partly verified", "status_reason": "The plan and reported total are available, but checking actual implementation of the schedule/meal conditions remains outstanding.", "missingness": "Actual 1-time schedule, meal/fasting conditions and dosing diaries unverified.", "uncertainty": "These items have different levels of verification; no new determination is made that an actual protocol deviation occurred.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Actual administration times/frequency, meal conditions, dosing diaries and plan-change information" }, { "item_id": "N24", "question_type": "Exposure and individual adherence", "question": "Does an increase in blood TDP establish individual adherence or RI benefit?", "needed": "Data on individual intake, exposure/TDP by period and handling of treatment deviations", "role": "Required", "role_reason": "Because biochemical exposure, individual dosing adherence and functional benefit are different outcomes.", "application_exception": "Do not add new exact numbers to the retained TDP increase or convert it into adherence by all participants, baseline deficiency or RI efficacy.", "criterion": "Distinguish the existence of an increased exposure marker from individual adherence, deviations by period and functional outcomes.", "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; own application; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed; M03 §3.2.4; own boundaries on extrapolation — Case-specific adaptation for Exposure and individual adherence. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Collect adherence records and exposure markers separately from the RI effect of interest, and prespecify how deviations will be handled.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "Increased biochemical exposure/TDP is retained, but individual adherence and dosing/deviations by period are unverified. A TDP increase itself does not establish RI benefit with P=0.63.", "condition_status": "Partly verified", "status_reason": "The context of an increased exposure marker is available, but individual implementation and contribution to function remain separate gaps.", "missingness": "Individual amounts actually taken, dosing/deviations by period and exact exposure values unverified.", "uncertainty": "An exposure marker cannot be used as clinical surrogate validation or automatic proof of functional benefit.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Data on individual intake, exposure/TDP by period and handling of treatment deviations" }, { "item_id": "N25", "question_type": "Reports and trial families", "question": "Have the thesis, P72, registration/ethics records and mirror been linked as the same F01?", "needed": "Identity linkage across reports, registrations and ethics/trial records, cohort overlap and original locations for each endpoint", "role": "Required", "role_reason": "Needed to avoid counting multiple reports of the same trial as independent replications or duplicated participant populations.", "application_exception": "This is a documentary comparison linking authors, institution, regimen/duration, the 34 completers and registered title, not verification at the level of individual identifiers.", "criterion": "Preserve the evidence linking documents in the same family and the original record of 1 direct family and 34 completers.", "basis": "Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an application developed for this work; M04 §4.6.1–4.6.2, M15 §15.3.1; own application — Case-specific adaptation for Reports and trial families. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Propose a subsequent review that maintains a family table and an endpoint/time-point/analysis linkage table centered on the original trial.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S06", "S07", "S08", "S18" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "F01 groups the Page Portsmouth oral-thiamine crossover trial records in S01–S08 and S18. There is 1 direct family and there are 34 completers. Do not count the thesis, poster, registration/ethics records and mirror as separate replications.", "condition_status": "Met", "status_reason": "The strong documentary identity linkage for the same trial and the rules preventing duplication have been retained.", "missingness": "Cohort comparison at the individual-identifier level and the number of analyzed RI pairs are unverified.", "uncertainty": "Matching document identities is not independent external clinical certification or proof that a confirmatory trial was conducted.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Identity linkage across reports, registrations and ethics/trial records, cohort overlap and original locations for each endpoint" }, { "item_id": "N26", "question_type": "Exception for between-study comparisons", "question": "Can between-study heterogeneity be estimated from the single verified direct family?", "needed": "Results, populations, dose/duration and analysis information for additional independent direct RI families", "role": "Required if multiple direct families are verified; currently not applicable", "role_reason": "Needed to avoid presenting multiple reports of the same trial as between-study consistency or replicated effects.", "application_exception": "Nonapplicability is limited to between-study comparison within the 1 verified direct family for the narrow RI question. Do not erase the unverified S19 candidate or other formulations as NA or conclude that there is 1 study worldwide.", "criterion": "Specify when comparisons between families apply and the manuscript's scope of a single direct family.", "basis": "M04 §4.6.1–4.6.2, M15 §15.3.1; own application; Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an application developed for this work — Case-specific adaptation for Exception for between-study comparisons. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "If a new direct family is acquired, separate its conditions and results and compare them according to prespecified heterogeneity hypotheses.", "current_reports": [ "S01", "S02", "S19" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "F01 is the only currently verified directly eligible RI family. The thesis, P72 and registration belong to the same family; a second direct result for estimating between-study consistency/heterogeneity has not been verified. Unverified candidates remain separate.", "condition_status": "Not applicable", "status_reason": "The applicability condition for between-study comparison is not met within the single currently verified family. Family linkage and candidate gaps have not been replaced by NA.", "missingness": "Additional independent direct RI results and the distribution of their conditions have not yet been acquired.", "uncertainty": "Nonapplicability within the current scope is not an exhaustive guarantee of study absence, sufficient replication or absence of inconsistency.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Results, populations, dose/duration and analysis information for additional independent direct RI families" }, { "item_id": "N27", "question_type": "Completion dates and posting events", "question": "Have the two registered completion dates and the results posting date been distinguished?", "needed": "Registry amendment history, definitions of completion dates, end-of-study report and posted-version information", "role": "Required (reporting history)", "role_reason": "Needed to avoid hiding differences in registry calendar dates or using the results posting date as the end of treatment.", "application_exception": "Do not turn the difference between 2011-07-04/2011-07-31 into an error in the nominal 8-week treatment period.", "criterion": "Preserve the completion dates in protocol/results metadata and the posting event in 2019 separately.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is self-designed; M08 Table 8.2.a, M04 §4.6.3; own application; M04 §4.5, §4.6.3; limits on the current data conversion reflect the user-defined scope and own design — Case-specific adaptation for Completion dates and posting events. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Compare event definitions and amendment history in the original registration/end-of-study report to verify the meaning of the two dates and the reason for their difference.", "current_reports": [ "S03", "S04", "S07" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The S03 protocol records global end as 2011-07-04, and S04 results metadata record global completion as 2011-07-31. The results posting date of 2019-03-20 is a separate event. The difference between the two completion dates is unresolved.", "condition_status": "Conflicting information", "status_reason": "The completion dates differ between the two registry records, and their definitions/reasons for change have not been verified.", "missingness": "Completion definitions, registry history, the body of the end-of-study attachment and the reason for the date difference are unverified.", "uncertainty": "Do not automatically expand different calendar events into a conflict about the nominal 8-week duration, RI measurement timing or clinical results.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Registry amendment history, definitions of completion dates, end-of-study report and posted-version information" }, { "item_id": "N28", "question_type": "Registered identifier labels", "question": "Have both HRA's n/a and the original registry's ISRCTN linkage been retained?", "needed": "Ethics/registry identifier amendment history, original ISRCTN record and explanation linking the same trial", "role": "Required (identity linkage)", "role_reason": "Needed to avoid hiding differences between identifier fields or claiming to have read the ISRCTN record text.", "application_exception": "Do not use HRA's n/a as proof of no ISRCTN or an unregistered trial; link the S03 identifier with the shared EudraCT/ethics number.", "criterion": "Distinguish the original registered identifier, the different ethics-record entry and the unacquired ISRCTN record text.", "basis": "Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an application developed for this work; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is self-designed; M08 Table 8.2.a, M04 §4.6.3; own application — Case-specific adaptation for Registered identifier labels. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Maintain a common trial identity table and compare the original registry/ethics history for the reason behind the different identifier entries.", "current_reports": [ "S03", "S05", "S08" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "S03 records ISRCTN30703970, whereas the ISRCTN field in S05 HRA says n/a. The shared EudraCT 2009-017537-21 and ethics identity are linked; the S08 record text could not be read previously because of a holding page/access failure.", "condition_status": "Conflicting information", "status_reason": "The same-trial identity linkage has been retained together with the discrepancy in the ISRCTN field.", "missingness": "The reason for the identifier-entry change and the S08 original record text/full history are unverified.", "uncertainty": "n/a or a holding page does not establish absence of a trial identity, current deletion or nonregistration.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Ethics/registry identifier amendment history, original ISRCTN record and explanation linking the same trial" }, { "item_id": "N29", "question_type": "Current and historical reading", "question": "Have reading the summaries and currently not reading the 21 external sources been separated?", "needed": "Records of exact locations in the retained inputs, material types/access, reading/byte hashes and dates", "role": "Required", "role_reason": "Needed to avoid promoting historical reading of abstracts, P72, registration/product information into direct reading in this work.", "application_exception": "Existence of a link/DOI is not full-text reading. Do not label access not attempted in this work as Inaccessible.", "criterion": "Record exact retained source-summary pointers/hashes, current access/acquisition/reading by material type and historical dates separately.", "basis": "Data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are self-designed; M04 §4.5, §4.6.3; limits on the current data conversion reflect the user-defined scope and own design — Case-specific adaptation for Current and historical reading. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "If actual sources are read in a specified subsequent update, add their material type, date, original bytes/location and status as a separate event.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S06", "S07", "S08", "S09", "S10", "S11", "S12", "S13", "S14", "S15", "S16", "S17", "S18", "S19", "S20", "S21" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The materials directly read in this work are the current Korean/structured archived manuscript. Access to the S01 abstract, S02 P72 text/images, S03 registration, S16 product information and similar materials on 2026-09-16 is historical. The relevant materials for the 21 external sources were not accessed, acquired or read in this work, and access was not attempted.", "condition_status": "Met", "status_reason": "Historical access successes/failures have been distinguished from current reading of retained summaries and recorded for each report and material type.", "missingness": "There is no current comprehensive verification of external public availability/existence, or direct verification in this work of original full texts, abstracts or registry text.", "uncertainty": "The SHA of a retained source summary is not the SHA of the external PDF/registry binary.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Records of exact locations in the retained inputs, material types/access, reading/byte hashes and dates" }, { "item_id": "N30", "question_type": "Gaps in major original reports", "question": "Can methods and original results in the full thesis and end-of-study attachment be compared?", "needed": "Full thesis, end-of-study report attachment, original RI tables/methods and appendix/analysis/safety data", "role": "Required (comparison of full methods)", "role_reason": "Because the institutional abstract and complete P72 conference abstract do not replace the full trial report.", "application_exception": "S02 covers the P72 abstract text/pages; do not claim to have read all 49 pages of the abstract collection or the full trial report. Separate historical S06/S07 failures from access not attempted now.", "criterion": "Record the scope of reports read at the time and content gaps in major original full texts that were not accessed.", "basis": "Data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are self-designed; M08 Table 8.2.a, M04 §4.6.3; own application — Case-specific adaptation for Gaps in major original reports. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Propose a document review that first acquires the permitted original full text/end-of-study attachment and compares the current RI methods, denominators, plan and safety information.", "current_reports": [ "S01", "S02", "S06", "S07" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "S01 is an institutional thesis abstract. S02 is a historical record of reading the complete P72 conference abstract text and page images, not the full trial report. Historical access failures for the S06 thesis PDF and S07 end-of-study attachment prevented comparison of the methods/results in their bodies.", "condition_status": "Unverified", "status_reason": "The bodies of the major full trial reports were not acquired within the retained access scope, and access has not been attempted in this work either.", "missingness": "Full methods, original RI tables, denominators, allocation/analysis/SAP and trial safety tables are unverified.", "uncertainty": "Do not reinterpret access failures at that time as current network failures or nonreporting throughout the article.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Full thesis, end-of-study report attachment, original RI tables/methods and appendix/analysis/safety data" }, { "item_id": "N31", "question_type": "Adjacent intravenous and blood-flow evidence", "question": "Has transfer of the acute intravenous BAVA in S09 to oral 8-week RI been avoided?", "needed": "Actual route, challenge conditions, BAVA definition and original methods in S09", "role": "Required (eligibility boundary)", "role_reason": "Needed to avoid merging evidence with the same thiamine name but different routes, challenge conditions and measures as independent replications of oral RI.", "application_exception": "In S09, the blood-flow augmentation with 100 mg intravenous thiamine after glucose challenge is neither brachial diameter FMD nor an oral RI effect.", "criterion": "Preserve only the adjacent evidence's route/measure differences and reasons for exclusion.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are self-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is self-designed; M04 §4.6.1–4.6.2, M15 §15.3.1; own application — Case-specific adaptation for Adjacent intravenous and blood-flow evidence. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "If an intravenous challenge-function question is requested, review it using a separate route/measure protocol and population.", "current_reports": [ "S09" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "S09 Arora 2006 is an acute blood-flow function experiment involving 100 mg intravenous thiamine after glucose challenge. BAVA is blood-flow augmentation, not brachial artery diameter FMD. Do not use it as an independent replication or benefit value for oral 8-week RI.", "condition_status": "Met", "status_reason": "The adjacent evidence has been separated from the selected RI result based on the currently retained differences in route/measure.", "missingness": "The acute experiment's full methods/specific values and a direct link to single-ingredient oral RI are unverified.", "uncertainty": "Exclusion of the adjacent study is not a new negative efficacy judgment for S09.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Actual route, challenge conditions, BAVA definition and original methods in S09" }, { "item_id": "N32", "question_type": "Dietary association", "question": "Has use of the dietary thiamine association in S10 as a single-ingredient causal effect been avoided?", "needed": "The dietary study's exposure, population, adjustment/timing and whether an actual treatment comparison exists", "role": "Required (eligibility boundary)", "role_reason": "Because dietary intake/status associations differ in exposure direction and design from randomized comparisons of additional supplementation.", "application_exception": "Do not extract the incremental effect of single-ingredient oral 300 mg/day from dietary associations with EPC/endothelial function.", "criterion": "Indicate the actual scope of exclusion based on observational design, dietary exposure and absence of a treatment comparison.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are self-designed; M08 §8.1–8.2.3; own application; M04 §4.6.1–4.6.2, M15 §15.3.1; own application — Case-specific adaptation for Dietary association. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Address dietary associations through separate prospective observation and supplementation efficacy alone through comparisons with matched background treatment.", "current_reports": [ "S10" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "S10 Wong concerns an observational association between daily dietary thiamine intake and EPC/endothelial function in type 2 diabetes. It is not a randomized trial of additional single-ingredient supplementation, so do not add it as a direct replication of 8-week RI.", "condition_status": "Met", "status_reason": "The actual differences in exposure/design are recorded, and the observational association has not been transferred into a causal treatment effect.", "missingness": "The original observation's full analyses, adjustment/timing data and the direct oral RI effect remain separate gaps.", "uncertainty": "Separating S10 from direct efficacy does not establish that the dietary association is null.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "The dietary study's exposure, population, adjustment/timing and whether an actual treatment comparison exists" }, { "item_id": "N33", "question_type": "Other B1 derivatives", "question": "Have benfotiamine FMD results been separated from ordinary-thiamine RI?", "needed": "Original ingredient, route, FMD/challenge conditions and identity of original results for each derivative", "role": "Required (ingredient boundary)", "role_reason": "Needed to avoid using data for different active molecules or smoking/meal challenge conditions as replications of the ordinary thiamine hydrochloride trial.", "application_exception": "Even within the same vitamin class, do not transfer benfotiamine in S11–S13 as RI values for the same ingredient/route. Do not describe title/index-level exclusion as verification of the full methods.", "criterion": "Record differences in active ingredients, challenge populations and measures, together with the actual access level for each material.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are self-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are self-designed; M04 §4.6.1–4.6.2, M15 §15.3.1; own application; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is self-designed — Case-specific adaptation for Other B1 derivatives. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Design/review derivative questions using separate ingredients and measures, and distinguish them from the current ordinary-thiamine RI family.", "current_reports": [ "S11", "S12", "S13" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "S11 is a 6-week benfotiamine crossover trial; S12/S13 also concern benfotiamine in smoking/AGE-meal challenge contexts. Do not use results for a different molecule/FMD as positive or negative replications of ordinary thiamine hydrochloride 8-week RI. S12/S13 were at the title/search-excerpt level at the time.", "condition_status": "Met", "status_reason": "Different active ingredients, challenge conditions and reading levels have been preserved without adding them as direct replications.", "missingness": "Their respective full methods, derivative contributions/original tables and the current direct RI result for ordinary thiamine are separate.", "uncertainty": "This exclusion is neither a new reassessment of derivative efficacy nor proof of no effect.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original ingredient, route, FMD/challenge conditions and identity of original results for each derivative" }, { "item_id": "N34", "question_type": "Combination products and attribution", "question": "Has use of the combination products in S14/S15 as a direct effect of adding B1 been avoided?", "needed": "Combination-product ingredients/populations, comparisons, report lineage/funding and actual evidence of the isolated contribution", "role": "Required (ingredient/duplication boundary)", "role_reason": "Because results involving multiple active ingredients and uncontrolled/healthy populations are not comparisons of thiamine alone in high-risk diabetes.", "application_exception": "Attribute Valerio's interests only to that family, and do not count the unclear link between S15 and earlier reports as independent replication.", "criterion": "Indicate combined ingredients, population/design, access level and gaps concerning possible overlap.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are self-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; own application; M04 §4.6.1–4.6.2, M15 §15.3.1; own application; Chamgap's own independence and attribution criteria. The official methods sections used in this pilot do not validate all of these detailed items — Case-specific adaptation for Combination products and attribution. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Keep combination products as separate questions; if the isolated contribution is asked about, propose a component comparison with matched background ingredients.", "current_reports": [ "S14", "S15" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "S14 concerns an uncontrolled pilot in healthy volunteers using a combination of Curcuma, CoQ10, black garlic, B1 and D3. S15 is also a search excerpt for a combination of L-cysteine, thiamine hydrochloride, B6 and ascorbic acid. Do not extract an isolated B1 effect, and retain the unverified linkage to earlier reports.", "condition_status": "Met", "status_reason": "Differences in combinations, populations and designs have been separated from gaps in report lineage.", "missingness": "The S15 full text, family relationship with earlier reports and isolated B1 contribution within the combination are unverified.", "uncertainty": "Do not assume that different combination products are equivalent independent replications or transfer their funding to F01.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Combination-product ingredients/populations, comparisons, report lineage/funding and actual evidence of the isolated contribution" }, { "item_id": "N35", "question_type": "Information levels of mirrors and reviews", "question": "Has use of the S18 mirror and S20/S21 reviews as original-trial numbers/funding been avoided?", "needed": "Original trial/registration funding, measurement methods/dates and linkage tables for studies/families included in reviews", "role": "Required (attribution boundary)", "role_reason": "Because discovery maps and disclosure excerpts do not replace direct verification of original-trial results/funding.", "application_exception": "Do not adopt the mirror's internal departmental funding, fasting/GTN or dates as facts verified in the original sources, or transfer review funding/disclosures to F01.", "criterion": "Link the information levels of original registrations/trials and secondary (2nd) discovery materials.", "basis": "Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an application developed for this work; Data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are self-designed; Chamgap's own independence and attribution criteria. The official methods sections used in this pilot do not validate all of these detailed items; M04 §4.6.1–4.6.2, M15 §15.3.1; own application — Case-specific adaptation for Information levels of mirrors and reviews. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Limit discovery materials to maps for tracing original trials, and compare original funding, methods and results separately.", "current_reports": [ "S18", "S20", "S21" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "S18 TrialScreen is a discovery mirror; its internal departmental funding, overnight fasting, GTN and dates were not adopted as verified original-trial facts. S20/S21 reviews are at the discovery/mapping level; do not transfer doses, effects or disclosures found only in reviews to F01 funding or independent replication.", "condition_status": "Met", "status_reason": "The attribution boundary between original materials and secondary (2nd) discovery information has been retained.", "missingness": "The full S20 page, original-trial funding/methods, review inclusion tables and disclosure linkages are unverified.", "uncertainty": "Existence of an excerpt does not mean that the original full text or funding has been verified or that a current comprehensive search has been completed.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original trial/registration funding, measurement methods/dates and linkage tables for studies/families included in reviews" }, { "item_id": "N36", "question_type": "Unverified registry candidate", "question": "Can the registered ingredient, status and results of NCT06322212 be established?", "needed": "Original NCT06322212 registry record, amendment history, ingredient/population, endpoints and actual results", "role": "Supplementary (candidate tracking)", "role_reason": "Needed to avoid inventing recruitment/formulation/numbers from an empty app screen or silently excluding the candidate.", "application_exception": "Do not establish current status, lack of posting or trial eligibility for a candidate for which only an HTML shell was seen previously.", "criterion": "Separate candidate identity from gaps in actual content and mark current access as not attempted.", "basis": "Data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are self-designed; M04 §4.5, §4.6.3; limits on the current data conversion reflect the user-defined scope and own design; M08 Table 8.2.a, M04 §4.6.3; own application — Case-specific adaptation for Unverified registry candidate. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Propose a subsequent review that first acquires the permitted official registry record and compares eligibility for the question and reported results.", "current_reports": [ "S19" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "S19 NCT06322212 is a candidate recorded as showing only the original screen shell after discovery in a search. Recruitment status, actual formulation, numbers and eligible FMD/RI results are unverified. Registry access was not attempted in this work.", "condition_status": "Unverified", "status_reason": "The candidate registry content has not been read, so the actual ingredient/results and current status cannot be established.", "missingness": "Original registry content, current status, formulation, endpoints and results/family relationships are unverified.", "uncertainty": "An unverified candidate does not establish ineligibility, study absence or current lack of posting.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original NCT06322212 registry record, amendment history, ingredient/population, endpoints and actual results" }, { "item_id": "N37", "question_type": "Funding and independence", "question": "Have a noncommercial sponsor and trial-specific funding, product supply and COI been distinguished?", "needed": "Declarations of trial funding, product supply, author employment/disclosed COI and sponsor roles", "role": "Supplementary; required for independence claims", "role_reason": "Needed to avoid converting unverified funding into confirmed independent/mixed funding or absence of bias.", "application_exception": "The blank S03 B.4 field and a noncommercial sponsor do not verify original-trial funding. Do not transfer declarations from the S18 mirror or the 2011 review.", "criterion": "Link what is verified about the sponsor to the unverified trial-specific funding and product/author relationships.", "basis": "Chamgap's own independence and attribution criteria. The official methods sections used in this pilot do not validate all of these detailed items; Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an application developed for this work — Case-specific adaptation for Funding and independence. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Disclose funding, product supply and analysis/publication roles in subsequent trials, and verify independent replication separately.", "current_reports": [ "S01", "S02", "S03", "S18", "S21" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "Trial-specific funding, product supply and conflicts of interest are unverified. The S03 B.4 funding field is blank; a noncommercial sponsor is not considered evidence of independent funding. The original I1 reflects handling as unverified and does not mean that actual mixed funding was verified.", "condition_status": "Unverified", "status_reason": "Sponsor identity or mirror/review excerpts cannot establish trial-specific funding or independence.", "missingness": "Original-trial funding, product supply, author COI and sponsor roles are unverified.", "uncertainty": "A funding gap is not a new judgment that commercial/mixed funding exists or that results are invalid.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Declarations of trial funding, product supply, author employment/disclosed COI and sponsor roles" }, { "item_id": "N38", "question_type": "Official oral-product information", "question": "Has transfer of the S16 product/route cautions to actual trial risks been avoided?", "needed": "Exact trial-product information, GI/hypersensitivity events by period, collection/denominators and route information", "role": "Supplementary; required for safety claims", "role_reason": "Because official cautions for a different product and era differ from events/frequencies observed in the trial.", "application_exception": "Flamingo 100 mg product information does not describe the actual Tyvera batch. Do not convert the predominantly parenteral hypersensitivity context into oral incidence.", "criterion": "Record the information level of official oral gastrointestinal/hypersensitivity cautions and the limits of applicability by product and route.", "basis": "M19 §19.1.2–19.2.4; own application; M19 §19.1.2–19.2.4; detailed distinctions are self-designed; Chamgap's own interpretive boundaries. M19 principles are referenced; no formal causality tool is applied; M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are self-designed — Case-specific adaptation for Official oral-product information. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Systematically collect harms for the exact product/route and report official cautions separately from trial observations.", "current_reports": [ "S16" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "S16 is the SmPC for Flamingo thiamine hydrochloride 100 mg tablets, a different product/era from registered Tyvera. The manuscript separately reflects gastrointestinal/hypersensitivity cautions for the oral product, without converting the predominantly parenteral hypersensitivity context into oral event incidence in this trial.", "condition_status": "Partly verified", "status_reason": "The identity of the official cautions and their product/route scope are available, but linkage to the exact trial product and actual risk denominators remains outstanding.", "missingness": "Cautions for the exact Tyvera product/batch, trial GI/hypersensitivity occurrence and denominators/durations are unverified.", "uncertainty": "Official cautions are not causal risk estimates from the actual trial, oral incidence or a new safety grade.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Exact trial-product information, GI/hypersensitivity events by period, collection/denominators and route information" }, { "item_id": "N39", "question_type": "UL and medication context", "question": "Has use of an unestablished UL and medication cautions as unlimited safety/efficacy been avoided?", "needed": "Updates to official source information, exact concomitant medications/exposure and safety data by baseline risk", "role": "Supplementary (general safety interpretation)", "role_reason": "Because an unestablished upper limit and general medication context do not guarantee safety testing or benefit for the exact high-risk regimen.", "application_exception": "Descriptions concerning furosemide and fluorouracil are not trial efficacy findings or self-dosing instructions. Do not infer from general information that all interactions have been excluded.", "criterion": "Separate the UL/medication context in general thiamine information from the unverified exact population and regimen.", "basis": "M19 §19.1.2–19.2.4; own application; Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is self-designed; Chamgap's own interpretive boundaries. M19 principles are referenced; no formal causality tool is applied — Case-specific adaptation for UL and medication context. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Design a safety study that records exact concomitant treatments and exposure, and separately compare the applicability of general information.", "current_reports": [ "S17" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "S17 provides general thiamine information in which absence of an established UL does not mean unlimited safety. Do not use wording about furosemide or fluorouracil as benefit from this trial or a dose recommendation. Exact concomitant treatments and long-term safety in the high-risk population are unverified.", "condition_status": "Partly verified", "status_reason": "The scope of general safety information is retained, but direct data on the exact regimen and concomitant treatments remain outstanding.", "missingness": "Interactions with specific concomitant treatments, rare/long-term risks and exposure denominators in the high-risk population are unverified.", "uncertainty": "Absence of a UL is not evidence of high-dose harmlessness, no interactions or authorization for personal dosing.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Updates to official source information, exact concomitant medications/exposure and safety data by baseline risk" }, { "item_id": "N40", "question_type": "Harms and discontinuations by period", "question": "Can event/person counts and discontinuation denominators be established for each crossover period?", "needed": "Exposure denominators, event/person counts such as GI/hypersensitivity events, discontinuations/serious events and collection/loss tables for each treatment period", "role": "Supplementary; required for safety claims", "role_reason": "Because the number of trial completers differs from harm collection/event frequency.", "application_exception": "Do not convert efficacy grade D, the 34 completers or the existence of general product information into 0 events, 0 discontinuations or NNH.", "criterion": "Link exposure by period, event/person counts, severity/reasons for discontinuation and collection/missingness.", "basis": "M19 §19.1.2–19.2.4; own application; M19 §19.1.2–19.2.4; detailed distinctions are self-designed; M19 §19.1.2–19.2.4, M04 §4.6.3; own application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each design are self-designed — Case-specific adaptation for Harms and discontinuations by period. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Systematically collect prespecified harms while distinguishing exposure by crossover period, recurrent events/person counts and reasons for discontinuation.", "current_reports": [ "S01", "S02", "S07", "S16", "S17" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "Trial adverse events, serious events, discontinuations and exposure/person denominators by period are unverified. Do not calculate harm incidence from the 34 completers or fill unverified events with 0.", "condition_status": "Unverified", "status_reason": "The selected regimen's actual harms tables and denominators/collection by period cannot be established from the current inputs.", "missingness": "Event/person counts, exposure time, collection by period and reasons for discontinuation/losses are unverified.", "uncertainty": "Unverified harms do not establish absence of events or safety, and do not erase the RI observations themselves.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Exposure denominators, event/person counts such as GI/hypersensitivity events, discontinuations/serious events and collection/loss tables for each treatment period" }, { "item_id": "N41", "question_type": "Long-term and subgroup extensions", "question": "Can 8-week RI be extended to long-term persistence, optimal doses or special populations?", "needed": "Post-discontinuation/long-term RI, direct dose comparisons, interactions with baseline status/special populations and long-term safety", "role": "Supplementary; required for the relevant extension", "role_reason": "Needed to avoid transferring the narrow short-term functional result to long-term efficacy/safety, special populations or dose optimization.", "application_exception": "Do not mechanically require every long-term/event/subgroup trial for the 8-week RI observation; extension questions require separate evidence.", "criterion": "Indicate separately the defined original duration and gaps in direct estimates/safety for extensions.", "basis": "M03 §3.2.1–3.2.4; details on dose, persistence and effect modification are self-designed; M03 §3.2.4; own boundaries on extrapolation; M19 §19.1.2–19.2.4; own application — Case-specific adaptation for Long-term and subgroup extensions. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "Plan long-term, dose and subgroup questions as separate prespecified comparative/follow-up studies and distinguish them from the current result.", "current_reports": [ "S01", "S02", "S16", "S17" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The current question concerns 8-week RI; long-term persistence, post-discontinuation effects, optimal dose, effect modification by baseline deficiency and long-term safety in special/high-risk populations are unverified. Do not use the study dose of 300 mg/day as a personal dosing instruction.", "condition_status": "Unverified", "status_reason": "Direct estimates/safety data for extensions beyond the selected short-term outcome have not been established.", "missingness": "Long-term/post-discontinuation outcomes, dose comparisons, prespecified subgroups and efficacy/safety in special populations are unverified.", "uncertainty": "Gaps in extensions neither invalidate the current 8-week RI numbers nor guarantee identical efficacy across all extensions.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Post-discontinuation/long-term RI, direct dose comparisons, interactions with baseline status/special populations and long-term safety" }, { "item_id": "N42", "question_type": "Historical search and update scope", "question": "Has use of the 42 web searches and 3 failed attempts as current comprehensive verification been avoided?", "needed": "Records of the historical search/access scope and verification of unpublished materials/candidates and correction/retraction/publication status", "role": "Required (scope limitation)", "role_reason": "Needed to avoid exaggerating the historical limited search and current conversion of retained content into a table as an up-to-date exhaustive search or guarantee of absence.", "application_exception": "The 42 are historical search records, not new searches or a study count. The 3 failed native searches are not API/network actions in this work either.", "criterion": "Specify the evidence cutoff, actual review date, historical search/access limitations and scope of correction/retraction updates.", "basis": "M04 §4.5, §4.6.3; limits on the current data conversion reflect the user-defined scope and own design; Data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are self-designed — Case-specific adaptation for Historical search and update scope. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "In an explicitly permitted subsequent update, record search sources, queries, inaccessible/negative materials and corrections/retractions by date.", "current_reports": [ "S01", "S02", "S19", "S20", "S21" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The retained evidence cutoff is 2026-09-16. At that time there were 42 general web searches and 3 failed native searches, with no guarantee of exhaustiveness. This work converts retained content and involves no new clinical search, original-source/registry/API query or correction/retraction query.", "condition_status": "Met", "status_reason": "Historical searches/failures have been distinguished from the current review scope, and statements of absence have been bounded.", "missingness": "Current comprehensive database coverage, all unpublished materials and the latest correction/retraction/candidate statuses are unverified.", "uncertainty": "The 1 direct family is a record within this retained scope, not a definitive count of unique trials worldwide.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Records of the historical search/access scope and verification of unpublished materials/candidates and correction/retraction/publication status" }, { "item_id": "N43", "question_type": "Original verdict and preparation status", "question": "Have D/28, the original axes and self-review been distinguished from a new table verdict or clinical certification?", "needed": "Current original verdict/axes, grading reasons, self-review/technical-publication history and canonical identity", "role": "Required (preservation traceability)", "role_reason": "Because the original verdict/score, document quality and completion of the current table are different statuses.", "application_exception": "R1 does not mean a confirmatory trial was conducted; I1 does not mean mixed funding was verified, E0 does not mean an exactly null effect, and CX does not mean important benefit was excluded. Document grade A is not external certification either.", "criterion": "Record the original D/28, Caution, historical handling/limitations of the axes, canonical URL and current local preparation scope.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed; M04 §4.5, §4.6.3; limits on the current data conversion reflect the user-defined scope and own design; Chamgap's own independence and attribution criteria. The official methods sections used in this pilot do not validate all of these detailed items — Case-specific adaptation for Original verdict and preparation status. This is not formal implementation or certification of the methods.", "condition_origin": "Development criteria individually designed with knowledge of the currently retained 3122 content. Neither blinded nor preregistered.", "proposed_research": "If an update of evidence/rules is requested, preserve the complete before-and-after original versions and version/decision reasons as a separate event, and update only the table's linked criteria within that scope.", "current_reports": [ "S01", "S02" ], "existence": "Identity of the currently retained manuscript/sources verified; the full current public availability/existence of external materials is unverified", "acquired_read": "Retained archived summary material read; external abstracts, full texts, registrations/source materials were not accessed, acquired or read in this work, and access was not attempted", "observation": "The original verdict is D, score 28, with a safety Caution. Preserve the historical B/S/R1/I1/E0/CX/B2 mapping without turning a single pilot into a confirmatory trial. Original document grade A is a single assistant's self-review, not formal GRADE or external clinical certification. Distinguish the existing publication identity of 2026-09-16 from the currently unpublished local table.", "condition_status": "Met", "status_reason": "The original verdict, explanations of axes, self-review, canonical URL/publication history and boundaries of the current preparation have been linked.", "missingness": "No new original full-text verification, independent review, clinical reassessment or publication of the public table was performed.", "uncertainty": "Meeting criteria or self-reviewing preparation does not raise/lower the original D/28 and Caution or create a new score.", "review_date": "2026-10-04", "reading_status": "Original source not read · Stored summary read", "additional_material": "Current original verdict/axes, grading reasons, self-review/technical-publication history and canonical identity" } ], "reports": [ { "report_id": "S01", "title": "Page GLJ. Oral thiamine supplementation in subjects with type 2 diabetes mellitus. MD thesis, December 2013.", "url": "https://researchportal.port.ac.uk/en/studentTheses/oral-thiamine-vitamin-b1-supplementation-in-subjects-with-type-2-/", "report_type": "Institutional thesis abstract", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F01", "independent_replication": false, "observed_result": "The institutional abstract of Page's MD thesis is linked to the identity of F01: oral thiamine hydrochloride, 300 mg/day, each period 8 weeks/2-week washout, high-risk type 2 diabetes, 34 completers and salbutamol-responsive RI. The general introduction to deficiency is not an actual baseline-deficiency measurement, and the full thesis text was not accessed historically.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Institutional thesis abstract webpage", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S01-M1", "url": "https://researchportal.port.ac.uk/en/studentTheses/oral-thiamine-vitamin-b1-supplementation-in-subjects-with-type-2-/", "parent_url": "https://researchportal.port.ac.uk/en/studentTheses/oral-thiamine-vitamin-b1-supplementation-in-subjects-with-type-2-/" } ], "links": [ { "label": "Source", "url": "https://researchportal.port.ac.uk/en/studentTheses/oral-thiamine-vitamin-b1-supplementation-in-subjects-with-type-2-/" } ] }, { "report_id": "S02", "title": "Page GLJ, Laight DW, Cummings MH. Thiamine supplementation in patients with Type 2 diabetes: effect on endothelial function and vascular inflammation. Poster P72. Diabetic Medicine 2013;30(Suppl 1):49–50.", "url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dme.12091_1", "report_type": "Conference P72 abstract PDF", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F01", "independent_replication": false, "observed_result": "The reported P72 8-week RI values are thiamine 5.3 ± 9.2 versus placebo 6.8 ± 6.9, P=0.63. The existing descriptive difference of −1.5 is not an adjusted paired causal estimate; units, SD/SE, CI and MCID are unverified. P72 text/page images were read at the time, but not the full trial report or the entire abstract collection. The DOI is at the abstract-collection level.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Conference abstract PDF", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S02-M1", "url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dme.12091_1", "parent_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dme.12091_1" }, { "material_type": "Full trial report and original analysis/safety data", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S02-M2", "url": null, "parent_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dme.12091_1" } ], "links": [ { "label": "Source", "url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dme.12091_1" } ] }, { "report_id": "S03", "title": "EU Clinical Trials Register protocol, 2009-017537-21, GB", "url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/GB", "report_type": "Official clinical-trial registry record", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F01", "independent_replication": false, "observed_result": "EudraCT 2009-017537-21 links ISRCTN30703970/PHT/2009/36. The registered Tyvera 100 mg product has a single active ingredient, and the registered primary (1st) endpoint is VCAM-1. Preserve the blank B.4 funding field, Yes for both parallel/crossover and global end 2011-07-04. The actual batch, SAP and full implementation of the plan are unverified.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full official registry web text", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S03-M1", "url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/GB", "parent_url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/GB" }, { "material_type": "Protocol, analysis plan and registry amendment history", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S03-M2", "url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/GB", "parent_url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/GB" } ], "links": [ { "label": "Source", "url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/GB" } ] }, { "report_id": "S04", "title": "EU Clinical Trials Register results metadata, 2009-017537-21", "url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/results", "report_type": "Official registry results metadata", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F01", "independent_replication": false, "observed_result": "The results metadata link the end-of-study attachment and record global completion 2011-07-31 and results posting date 2019-03-20. The discrepancy with 2011-07-04 in the protocol remains, and the attachment text could not be read historically. Do not infer safety/effect values from metadata.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Official results-metadata webpage", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S04-M1", "url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/results", "parent_url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/results" }, { "material_type": "End-of-study report attachment", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S04-M2", "url": "https://www.clinicaltrialsregister.eu/ctr-search/rest/download/result/attachment/2009-017537-21/1/26416", "parent_url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/results" } ], "links": [ { "label": "Source", "url": "https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/results" } ] }, { "report_id": "S05", "title": "UK HRA: Thiamine supplementation in type 2 diabetes", "url": "https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/thiamine-supplementation-in-type-2-diabetes/", "report_type": "Official ethics research summary", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F01", "independent_replication": false, "observed_result": "HRA links IRAS33021, REC09/H0504/137 and EudraCT2009-017537-21 and records planned crossover visits/a schedule of 1 time per 1 day. It does not verify actual 1-time administration or adherence implementation. Preserve n/a in the ISRCTN field as a discrepancy with the S03 identifier.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Ethics research-summary webpage", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S05-M1", "url": "https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/thiamine-supplementation-in-type-2-diabetes/", "parent_url": "https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/thiamine-supplementation-in-type-2-diabetes/" } ], "links": [ { "label": "Source", "url": "https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/thiamine-supplementation-in-type-2-diabetes/" } ] }, { "report_id": "S06", "title": "Page MD thesis full PDF, linked from university record", "url": "https://researchportal.port.ac.uk/files/5949788/GPage_MD_for_printing.pdf", "report_type": "Full thesis PDF", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F01", "independent_replication": false, "observed_result": "The thesis PDF linked from the institutional record could not be read for its full methods/results historically because of 403/internal errors and download failures. Only initial PDF metadata and the original identity are available; external access has not been attempted in this work either.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full thesis PDF", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S06-M1", "url": "https://researchportal.port.ac.uk/files/5949788/GPage_MD_for_printing.pdf", "parent_url": "https://researchportal.port.ac.uk/files/5949788/GPage_MD_for_printing.pdf" } ], "links": [ { "label": "Source", "url": "https://researchportal.port.ac.uk/files/5949788/GPage_MD_for_printing.pdf" } ] }, { "report_id": "S07", "title": "Thiamine End of Study Report attachment", "url": "https://www.clinicaltrialsregister.eu/ctr-search/rest/download/result/attachment/2009-017537-21/1/26416", "report_type": "End-of-study report attachment", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F01", "independent_replication": false, "observed_result": "The contents of the end-of-study report attachment linked by S04 could not be read at the time because of application/octet-stream/download failure. No safety information or numbers were adopted from that attachment, and access has not been attempted in this work either.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "End-of-study report attachment", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S07-M1", "url": "https://www.clinicaltrialsregister.eu/ctr-search/rest/download/result/attachment/2009-017537-21/1/26416", "parent_url": "https://www.clinicaltrialsregister.eu/ctr-search/rest/download/result/attachment/2009-017537-21/1/26416" } ], "links": [ { "label": "Source", "url": "https://www.clinicaltrialsregister.eu/ctr-search/rest/download/result/attachment/2009-017537-21/1/26416" } ] }, { "report_id": "S08", "title": "ISRCTN30703970 trial record", "url": "https://www.isrctn.com/ISRCTN30703970", "report_type": "Official ISRCTN registration", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F01", "independent_replication": false, "observed_result": "The identity ISRCTN30703970 is verified in S03, but the S08 record text could not be read directly historically because of a holding page/access failure and failure of the PDF alternative. The secondary (2nd) mirror is for discovery and is not promoted into implementation/results from the original registry.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full official registry web text", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S08-M1", "url": "https://www.isrctn.com/ISRCTN30703970", "parent_url": "https://www.isrctn.com/ISRCTN30703970" }, { "material_type": "Registry amendment history and results/protocol", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S08-M2", "url": "https://www.isrctn.com/ISRCTN30703970", "parent_url": "https://www.isrctn.com/ISRCTN30703970" } ], "links": [ { "label": "Source", "url": "https://www.isrctn.com/ISRCTN30703970" } ] }, { "report_id": "S09", "title": "Arora et al. Thiamine improves endothelium-dependent vasodilatation in the presence of hyperglycemia. Ann Vasc Surg 2006;20:653–658.", "url": "https://pure.johnshopkins.edu/en/publications/thiamine-vitamin-bsub1sub-improves-endothelium-dependent-vasodila/", "report_type": "Institutional original-article abstract", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F02", "independent_replication": null, "observed_result": "Arora 2006 is an acute experiment involving 100 mg intravenous thiamine after glucose challenge. BAVA is blood-flow augmentation, not brachial diameter FMD, and is not counted as an independent replication of oral 8-week RI. Access at the time was at the institutional-abstract level.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Institutional article-abstract webpage", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S09-M1", "url": "https://pure.johnshopkins.edu/en/publications/thiamine-vitamin-bsub1sub-improves-endothelium-dependent-vasodila/", "parent_url": "https://pure.johnshopkins.edu/en/publications/thiamine-vitamin-bsub1sub-improves-endothelium-dependent-vasodila/" }, { "material_type": "Original article full text and methods/source data", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S09-M2", "url": null, "parent_url": "https://pure.johnshopkins.edu/en/publications/thiamine-vitamin-bsub1sub-improves-endothelium-dependent-vasodila/" } ], "links": [ { "label": "Source", "url": "https://pure.johnshopkins.edu/en/publications/thiamine-vitamin-bsub1sub-improves-endothelium-dependent-vasodila/" } ] }, { "report_id": "S10", "title": "Wong et al. Daily intake of thiamine correlates with the circulating level of endothelial progenitor cells and the endothelial function in patients with type II diabetes.", "url": "https://pubmed.ncbi.nlm.nih.gov/18925614/", "report_type": "Original article abstract", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F03", "independent_replication": null, "observed_result": "Wong's observational association between daily dietary thiamine intake and EPC/endothelial function is not a randomized comparison of single-ingredient supplementation. Do not add it to the selected RI direct-efficacy families, and preserve the abstract-level access at the time.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Article abstract", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S10-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/18925614/", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/18925614/" }, { "material_type": "Original article full text and methods/source data", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S10-M2", "url": null, "parent_url": "https://pubmed.ncbi.nlm.nih.gov/18925614/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/18925614/" } ] }, { "report_id": "S11", "title": "Stirban A, Pop A, Tschoepe D. A randomized, double-blind, crossover, placebo-controlled trial of 6 weeks benfotiamine treatment on postprandial vascular function and variables of autonomic nerve function in Type 2 diabetes. Diabet Med. 2013;30(10):1204–1208.", "url": "https://pubmed.ncbi.nlm.nih.gov/23701274/", "report_type": "Original article abstract", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F04", "independent_replication": null, "observed_result": "Stirban 2013 is a 6-week benfotiamine crossover trial. Do not borrow fasting/meal-challenge FMD results for a different active ingredient as ordinary thiamine hydrochloride RI. Access at the time was at the PubMed-abstract level.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Article abstract", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S11-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/23701274/", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/23701274/" }, { "material_type": "Original article full text and methods/source data", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S11-M2", "url": null, "parent_url": "https://pubmed.ncbi.nlm.nih.gov/23701274/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/23701274/" } ] }, { "report_id": "S12", "title": "Benfotiamine counteracts smoking-induced vascular dysfunction in healthy smokers (2012)", "url": "https://onlinelibrary.wiley.com/doi/pdf/10.1155/2012/968761", "report_type": "Original article title and search excerpt", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F05", "independent_replication": null, "observed_result": "This is benfotiamine evidence in healthy smokers, excluded by ingredient at the title/search-excerpt level. The alternative PMC page presented recaptcha; no verification of the full methods is claimed. Do not use it as replication of ordinary-thiamine RI.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Article title and index excerpt", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S12-M1", "url": "https://onlinelibrary.wiley.com/doi/pdf/10.1155/2012/968761", "parent_url": "https://onlinelibrary.wiley.com/doi/pdf/10.1155/2012/968761" }, { "material_type": "Original article full web text", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S12-M2", "url": "https://onlinelibrary.wiley.com/doi/pdf/10.1155/2012/968761", "parent_url": "https://onlinelibrary.wiley.com/doi/pdf/10.1155/2012/968761" } ], "links": [ { "label": "Source", "url": "https://onlinelibrary.wiley.com/doi/pdf/10.1155/2012/968761" } ] }, { "report_id": "S13", "title": "Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products (2006)", "url": "https://diabetesjournals.org/care/article/29/9/2064/24125/Benfotiamine-Prevents-Macro-and-Microvascular", "report_type": "Original article title and search excerpt", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F06", "independent_replication": null, "observed_result": "The vascular-function evidence after an AGE meal concerns benfotiamine, a different ingredient. Only the title/search excerpt was verified at the time; do not promote doses/results found only in reviews into facts verified in the original source.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Article title and index excerpt", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S13-M1", "url": "https://diabetesjournals.org/care/article/29/9/2064/24125/Benfotiamine-Prevents-Macro-and-Microvascular", "parent_url": "https://diabetesjournals.org/care/article/29/9/2064/24125/Benfotiamine-Prevents-Macro-and-Microvascular" }, { "material_type": "Original article full web text", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S13-M2", "url": "https://diabetesjournals.org/care/article/29/9/2064/24125/Benfotiamine-Prevents-Macro-and-Microvascular", "parent_url": "https://diabetesjournals.org/care/article/29/9/2064/24125/Benfotiamine-Prevents-Macro-and-Microvascular" } ], "links": [ { "label": "Source", "url": "https://diabetesjournals.org/care/article/29/9/2064/24125/Benfotiamine-Prevents-Macro-and-Microvascular" } ] }, { "report_id": "S14", "title": "Valerio V et al. Oral nutraceutical intervention to improve endothelial function: Evidence from in vitro and pilot clinical studies. Biomed Pharmacother. 2025;191:118552.", "url": "https://pubmed.ncbi.nlm.nih.gov/40957246/", "report_type": "Original article abstract", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F07", "independent_replication": null, "observed_result": "Valerio 2025 concerns an uncontrolled pilot in healthy volunteers using a combination of Curcuma, CoQ10, black garlic, B1 and D3. Do not transfer that family's disclosures to F01; it is not a comparative result for B1 alone. The record states that the abstract was read at the time and the full publisher text was blocked.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Article abstract", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S14-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/40957246/", "parent_url": "https://pubmed.ncbi.nlm.nih.gov/40957246/" }, { "material_type": "Original article full web text and methods/source data", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S14-M2", "url": null, "parent_url": "https://pubmed.ncbi.nlm.nih.gov/40957246/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/40957246/" } ] }, { "report_id": "S15", "title": "Antioxidant formulation preprint involving L-cysteine, thiamine hydrochloride, pyridoxine and ascorbic acid (2025)", "url": "https://www.preprints.org/manuscript/202501.0355/v1/download", "report_type": "Preprint title and search excerpt", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F08", "independent_replication": null, "observed_result": "This is a search excerpt for a combination of L-cysteine, thiamine hydrochloride, B6 and ascorbic acid. It is not an assessment of the entire full text; its relationship with an earlier stiffness report is unverified, so it is not counted as independent replication.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Preprint index excerpt", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S15-M1", "url": "https://www.preprints.org/manuscript/202501.0355/v1/download", "parent_url": "https://www.preprints.org/manuscript/202501.0355/v1/download" }, { "material_type": "Full preprint PDF", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S15-M2", "url": "https://www.preprints.org/manuscript/202501.0355/v1/download", "parent_url": "https://www.preprints.org/manuscript/202501.0355/v1/download" } ], "links": [ { "label": "Source", "url": "https://www.preprints.org/manuscript/202501.0355/v1/download" } ] }, { "report_id": "S16", "title": "Thiamine Hydrochloride 100 mg Tablets, Flamingo Pharma UK Ltd: Summary of Product Characteristics", "url": "https://www.medicines.org.uk/emc/product/13528/smpc", "report_type": "Official oral-product information", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": null, "independent_replication": null, "observed_result": "The SmPC for Flamingo thiamine hydrochloride 100 mg tablets concerns a different product/era from registered Tyvera. The manuscript separately reflects gastrointestinal/hypersensitivity cautions without converting the predominantly parenteral hypersensitivity context into oral event incidence. This is not the actual trial batch or a period-specific safety table.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full official product-information web text", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S16-M1", "url": "https://www.medicines.org.uk/emc/product/13528/smpc", "parent_url": "https://www.medicines.org.uk/emc/product/13528/smpc" }, { "material_type": "Original harm data for the exact trial product and route", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S16-M2", "url": null, "parent_url": "https://www.medicines.org.uk/emc/product/13528/smpc" } ], "links": [ { "label": "Source", "url": "https://www.medicines.org.uk/emc/product/13528/smpc" } ] }, { "report_id": "S17", "title": "NIH Office of Dietary Supplements: Thiamin—Health Professional Fact Sheet", "url": "https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/", "report_type": "Official nutrition fact sheet", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": null, "independent_replication": null, "observed_result": "The lack of an established UL in NIH ODS is not proof of unlimited safety. Do not use the furosemide/fluorouracil context as benefit from this trial or a dosing instruction. Safety denominators/durations for the exact high-risk regimen are separately unverified.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full official fact-sheet web text", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S17-M1", "url": "https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/", "parent_url": "https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/" }, { "material_type": "Original safety data for the exact population, concomitant treatments and regimen", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S17-M2", "url": null, "parent_url": "https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/" } ], "links": [ { "label": "Source", "url": "https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/" } ] }, { "report_id": "S18", "title": "TrialScreen mirror for ISRCTN30703970", "url": "https://trialscreen.org/trials/phase-2-type-diabetes-mellitus-thiamine-supplementation-trial-isrctn30703970", "report_type": "Secondary (2nd) registry-mirror search excerpt", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F01", "independent_replication": false, "observed_result": "TrialScreen's internal departmental funding, overnight fasting, GTN protocol and dates were not adopted as facts verified in original materials. It is a discovery clue for the same F01, not an independent trial or original funding evidence.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Registry-mirror index excerpt", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S18-M1", "url": "https://trialscreen.org/trials/phase-2-type-diabetes-mellitus-thiamine-supplementation-trial-isrctn30703970", "parent_url": "https://trialscreen.org/trials/phase-2-type-diabetes-mellitus-thiamine-supplementation-trial-isrctn30703970" } ], "links": [ { "label": "Source", "url": "https://trialscreen.org/trials/phase-2-type-diabetes-mellitus-thiamine-supplementation-trial-isrctn30703970" } ] }, { "report_id": "S19", "title": "ClinicalTrials.gov NCT06322212", "url": "https://clinicaltrials.gov/study/NCT06322212", "report_type": "Official registry candidate", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": "F09", "independent_replication": null, "observed_result": "For NCT06322212, only an HTML screen shell appeared after search discovery. Recruitment status, actual formulation, numerical values and eligible FMD/RI results are unverified. Preserve the candidate without a current external query.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Full official registry web text", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S19-M1", "url": "https://clinicaltrials.gov/study/NCT06322212", "parent_url": "https://clinicaltrials.gov/study/NCT06322212" }, { "material_type": "Registry amendment history and results/protocol", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S19-M2", "url": "https://clinicaltrials.gov/study/NCT06322212", "parent_url": "https://clinicaltrials.gov/study/NCT06322212" } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT06322212" } ] }, { "report_id": "S20", "title": "Serra et al. Thiamine/benfotiamine cardiovascular evidence review, IJMS 2025;26:3932", "url": "https://www.mdpi.com/1422-0067/26/9/3932", "report_type": "Secondary (2nd) review search excerpt", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": null, "independent_replication": null, "observed_result": "The Serra 2025 review is a discovery map based on search excerpts, with an error accessing the full page. Do not adopt doses, ingredients or effects found only in the review as facts verified in original sources. Preserve the original URL without claiming new DOI verification.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Review index excerpt", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S20-M1", "url": "https://www.mdpi.com/1422-0067/26/9/3932", "parent_url": "https://www.mdpi.com/1422-0067/26/9/3932" }, { "material_type": "Review full web text and included-trial table", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S20-M2", "url": "https://www.mdpi.com/1422-0067/26/9/3932", "parent_url": "https://www.mdpi.com/1422-0067/26/9/3932" } ], "links": [ { "label": "Source", "url": "https://www.mdpi.com/1422-0067/26/9/3932" } ] }, { "report_id": "S21", "title": "Page, Laight and Cummings review (2011)", "url": "https://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2011.02680.x", "report_type": "Secondary (2nd) review bibliographic/disclosure excerpt", "existence": "Retained source identity verified; full current external public availability/existence unverified", "acquired_read": "Retained archived summary material read; access to the relevant external materials was not attempted, and they were not acquired or read in this work", "study_family": null, "independent_replication": null, "observed_result": "The Page, Laight and Cummings 2011 review is discovery material at the bibliographic/disclosure-excerpt level. Do not infer verified funding for the F01 trial from clinical estimates or the review's disclosures.", "result_level": "Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work", "source_evidence_date": "2026-09-16", "materials": [ { "material_type": "Review bibliographic/index excerpt", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S21-M1", "url": "https://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2011.02680.x", "parent_url": "https://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2011.02680.x" }, { "material_type": "Review full web text and included-trial table", "public_status": "Currently unverified (no external query in this work)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-04T23:25:22.339763+09:00", "qualification": "What has been read now is the retained archived manuscript describing this material. Historical success/failure records are not promoted into external reading in this work.", "material_id": "S21-M2", "url": "https://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2011.02680.x", "parent_url": "https://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2011.02680.x" } ], "links": [ { "label": "Source", "url": "https://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2011.02680.x" } ] } ], "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": "Historical reuse of the actual HTML copies, SHA and methodological principles retained in 1585. This is not new reading of full methodological texts, formal implementation or clinical certification in this work." }, { "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": "Historical reuse of the actual HTML copies, SHA and methodological principles retained in 1585. This is not new reading of full methodological texts, formal implementation or clinical certification in this work." }, { "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": "Historical reuse of the actual HTML copies, SHA and methodological principles retained in 1585. This is not new reading of full methodological texts, formal implementation or clinical certification in this work." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Historical reuse of the actual HTML copies, SHA and methodological principles retained in 1585. This is not new reading of full methodological texts, formal implementation or clinical certification in this work." }, { "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": "Historical reuse of the actual HTML copies, SHA and methodological principles retained in 1585. This is not new reading of full methodological texts, formal implementation or clinical certification in this work." } ], "status_dictionary": { "Met": "The relevant distinctions in identity, boundaries and retained records have been verified. This does not establish clinical benefit/safety or constitute official certification.", "Partly verified": "Some design details, numerical values and methods are retained, but dimensions needed for verification remain unresolved.", "Unverified": "The required values cannot be established within the retained scope read. This does not mean absence of all studies, an effect of 0 or 0 events.", "Conflicting information": "Design checkboxes, completion dates and identifier entries in the original registration differ across the relevant records. Do not expand this into a conflict over actual treatment durations or clinical effects as a whole.", "Not applicable": "Between-study comparison does not apply within the single verified direct family. Do not fill in unverified candidates or other formulations as independent results.", "Not reported": "Limited to an information gap at the retained location actually read; do not expand this into nonreporting throughout the external article.", "Inaccessible": "Requires an actual failed access attempt in the current work. External access not attempted in this work differs from historical access failure.", "Review incomplete": "Pending individual review during table preparation, distinct from unverified/unread materials." }, "study_overlap": { "state": "Preserve the manuscript's family linkage, single direct family and 34 completers. The 21 reports are not 21 independent trials; do not newly add unique participant counts across other preparations/combination candidates. For this fixed question, there is 1 direct trial family and there are 34 completers. The number of unique randomized participants and the number of analyzed RI pairs are unverified. Do not extend these to the total unique trials or total participants across all related materials.", "unique_trial_count": null, "unique_participant_count": null, "reason": "Preserve the manuscript's family linkage, single direct family and 34 completers. The 21 reports are not 21 independent trials; do not newly add unique participant counts across other preparations/combination candidates. For this fixed question, there is 1 direct trial family and there are 34 completers. The number of unique randomized participants and the number of analyzed RI pairs are unverified. Do not extend these to the total unique trials or total participants across all related materials. / F01 (S01, S02, S03, S04, S05, S06, S07, S08, S18): Page Portsmouth oral thiamine T2D crossover · Author/institution, identical oral 300mg/day, 8-week periods, 2-week washout, study n34 and endpoint suite; registry full title matches thesis. · Thesis, poster, ethics and registry are one family. 34 participants are not 68 independent participants. · strong_documentary_match; no subject-level identifiers available / F02 (S09): Arora 2006 acute IV glucose-challenge blood-flow experiment · Wrong route; blood-flow augmentation not diameter FMD; acute challenge population/sequence different / F03 (S10): Wong 2008 dietary intake observational study · No controlled oral supplementation comparison / F04 (S11): Stirban 2013 benfotiamine crossover · Different chemical entity / F05 (S12): Benfotiamine smoking challenge 2012 · Different chemical entity and challenge population / F06 (S13): Benfotiamine AGE-meal 2006 · Different chemical entity; title-level exclusion / F07 (S14): Valerio 2025 combination nutraceutical pilot · Combination and healthy-volunteer proof-of-concept; not isolated B1 control / F08 (S15): Antioxidant combination preprint 2025 · Combination product; possible earlier report linkage unverified / F09 (S19): NCT06322212 unresolved registry candidate · Record contents inaccessible; no eligible endothelial-result report verified" }, "history": [ { "date": "2026-11-07", "kind": "Separation of public-facing display and data", "view_version": "1.0", "change": "Public-facing display and data were prepared from the existing 43 items. No new clinical search, verification-status change or scoring was performed." } ], "language": "en", "translation_date": "2026-11-07" }