# Ordinary thiamine (vitamin B1), hydrochloride × Eight-week salbutamol-responsive digital reflective-index response Verdict 3122 · Evidence Check Stored-material review date: 2026-10-04 Original evidence date: 2026-09-16 Review-criteria version: v3122-ORAL-THIAMINE-RI-1.1 Public page/material preparation date: 2026-11-07 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: Adults with type 2 diabetes at high cardiovascular risk; actual mean age 61 years; baseline deficiency and numerically established endothelial dysfunction unverified - Ingredient, formulation and route: 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 - Measured outcome: 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 - Questions outside this scope: 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 ## Checklist items ### N01 · Which population, regimen and 8-week functional response does the independent table address? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: The exact current original claim has been linked to the boundary of the actual direct trial result. This Met status does not establish benefit. - Reason for missing information: Original RI units, variance, denominator, adjusted effect and related gaps remain in separate rows. - Required materials and conditions: Original locations of the current claim, PICOT, surrogate measure and excluded questions - Materials to obtain first: Original locations of the current claim, PICOT, surrogate measure and excluded questions - Further research: In subsequent research, first fix the population, oral regimen, placebo and RI measurement time, and distinguish other outcomes alongside them. - Conditions for verification: Link the selected population, actual comparison, regimen and timing to the original identity of digital RI. - Why this condition is needed: Needed to distinguish the entire ordinary-thiamine page from the selected functional outcome. - Application exceptions: Preserve the original claim exactly as recorded at /ko/effect, without automatically creating new efficacy subclaims for FMD, clinical events or TDP. - Remaining uncertainty: Verifying the identity of this table's question differs from clinical certification of FMD or event prevention. - Referenced methods: 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. - Related sources: S01, S02 ### N02 · Have the single registered active ingredient and the actual product batch been distinguished? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: The active ingredient/registered product is retained, but detailed information on the actual trial product remains to be verified. - Reason for missing information: Actual manufacturing, batch, excipients and purity/release form unverified. - Required materials and conditions: Actual trial product ingredient list, batch, excipients and manufacturing-origin information - Materials to obtain first: Actual trial product ingredient list, batch, excipients and manufacturing-origin information - Further research: Propose a replication procedure that obtains product analyses and batch records and verifies actual administration of the single active ingredient. - Conditions for verification: Record ordinary thiamine hydrochloride and the registered product identity separately from the unverified actual batch/excipients. - Why this condition is needed: Because active-ingredient identity and the actual formulation/batch do not have the same level of verification. - Application exceptions: Do not substitute Flamingo product information from a different era for registered Tyvera, or automatically equate it with benfotiamine or combination products. - Remaining uncertainty: Ingredient lists and safety wording for different products cannot be transferred as facts about the current trial product. - Referenced methods: 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. - Related sources: S01, S03, S16 ### N03 · Have the reported 300 mg/day and the free-thiamine equivalent been distinguished? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: The reported total is within the verified scope, but conversion to the active amount and the actual schedule remain unresolved. - Reason for missing information: Hydrochloride/free-thiamine conversion and actual amount taken 1 time/frequency unverified. - Required materials and conditions: Actual dose records, product content/units, 1-time dosing schedule and amount actually taken - Materials to obtain first: Actual dose records, product content/units, 1-time dosing schedule and amount actually taken - Further research: After verifying actual administration records and content units, address any necessary dose comparison under a separate protocol. - Conditions for verification: Preserve the reported daily total and mark the free-thiamine conversion and actual 1-time schedule as unverified. - Why this condition is needed: Needed to avoid converting the nominal total hydrochloride amount into the active contribution or an optimal personal dose. - Application exceptions: 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. - Remaining uncertainty: The study total is not a personal dosing instruction or evidence of an optimal dose. - Referenced methods: 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. - Related sources: S01, S03 ### N04 · Have each 8-week treatment period and the 2-week washout been linked to the outcome time? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: The retained nominal treatment/washout periods and selected time point have been accurately linked. - Reason for missing information: Actual visit dates, complete exposure in each period and long-term persistence data are unverified. - Required materials and conditions: Information on administration and visit schedules by period and RI measurement times - Materials to obtain first: Information on administration and visit schedules by period and RI measurement times - Further research: Check implementation of each treatment and washout against visit/exposure records, and plan long-term persistence questions under separate follow-up. - Conditions for verification: Link each 8-week period, the 2-week washout and RI at the end of treatment to their original locations. - Why this condition is needed: Needed to avoid confusing the crossover trial's two treatment periods, washout and original outcome time as the same total duration. - Application exceptions: Do not turn the discrepancy in registered calendar completion dates into a conflict over the reported treatment duration of 8 weeks. - Remaining uncertainty: A Met status for duration reporting does not establish that washout excluded carryover or that long-term efficacy criteria were met. - Referenced methods: 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. - Related sources: S01, S02 ### N05 · Have the actual high-risk adults with type 2 diabetes and the registered eligibility plan been distinguished? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: The basic identity of the actual population is available, but detailed baseline characteristics and representativeness remain to be verified. - Reason for missing information: Baseline characteristics by sequence, actual fulfillment of eligibility in all participants and numerically established endothelial dysfunction unverified. - Required materials and conditions: Baseline characteristics by group/sequence, actual inclusion/exclusion flow and definitions of risk and endothelial function - Materials to obtain first: Baseline characteristics by group/sequence, actual inclusion/exclusion flow and definitions of risk and endothelial function - Further research: In subsequent comparisons, prespecify risk selection and baseline vascular function and disclose actual participant characteristics. - Conditions for verification: Distinguish the actual high-risk adult population with type 2 diabetes and mean age from the remaining baseline-data gaps. - Why this condition is needed: Needed to avoid promoting planned registered selection criteria into actual characteristics of all participants or baseline endothelial dysfunction. - Application exceptions: Verify the target scope from registered eligibility/the institutional abstract, without inferring detailed diagnoses or the population mix for all participants. - Remaining uncertainty: The registration plan does not replace actual composition data and does not automatically extend to all adults with diabetes. - Referenced methods: 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. - Related sources: S01, S02, S03 ### N06 · Can baseline thiamine deficiency and the conditions for additional supplementation be established? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: Actual deficiency classification and intake data for participants in the direct trial cannot be established from the retained inputs. - Reason for missing information: Baseline deficiency/nondeficiency, thresholds, total intake and nutritional subgroups unverified. - Required materials and conditions: Baseline thiamine/TDP, deficiency thresholds, dietary/supplement intake and prespecified stratification data - Materials to obtain first: Baseline thiamine/TDP, deficiency thresholds, dietary/supplement intake and prespecified stratification data - Further research: Measure baseline status and assess effect modification by deficiency status in a separately planned, prespecified analysis. - Conditions for verification: Retain the actual level of verification of baseline status, deficiency criteria and total intake. - Why this condition is needed: Needed to distinguish possible correction of deficiency from the effect of additional supplementation in a population of unknown status. - Application exceptions: Do not use the thesis abstract's general discussion of deficiency as an actual measurement of deficiency in participants. - Remaining uncertainty: This gap does not mean that all participants were deficient or all were sufficient, or that there was no effect. - Referenced methods: 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. - Related sources: S01, S02 ### N07 · Have the placebo comparison and background-medication balance between periods been distinguished? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: The placebo comparison is identified, but actual differences in concomitant treatment between periods and their handling have not been verified. - Reason for missing information: Actual period-specific distributions of concomitant medications, disease changes and rescue treatment, and their effects on analysis, unverified. - Required materials and conditions: Information on medications, rescue treatment, disease status/changes and their handling for the effect of interest by period - Materials to obtain first: Information on medications, rescue treatment, disease status/changes and their handling for the effect of interest by period - Further research: Propose a comparison that records common treatment and prespecifies how period-specific changes and rescue treatment will be handled in analysis. - Conditions for verification: Distinguish the actual placebo comparison from gaps in period-specific concomitant/rescue treatment and the handling of changes. - Why this condition is needed: Because changes in background diabetes/cardiovascular treatment may be mixed with the contribution of thiamine. - Application exceptions: Even in a crossover comparison in the same participants, do not assume that all medication and disease changes were identical between periods. - Remaining uncertainty: The crossover design itself is not evidence that it removed changes in concomitant treatment/disease over time. - Referenced methods: 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. - Related sources: S01, S02 ### N08 · Have the actual crossover design and the registry's parallel/crossover checkboxes been distinguished? Verification status: Conflicting information Reading scope: 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 - Current findings: 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. - Why unverified: The discrepancy in simultaneous design checkmarks within the same registration is retained. Do not change the actual treatment comparison into a new parallel design. - Reason for missing information: Protocol/SAP, reasons for registry amendments and original explanation of the checkmarks unverified. - Required materials and conditions: Full protocol, registry amendment history, actual allocation sequences and design explanation - Materials to obtain first: Full protocol, registry amendment history, actual allocation sequences and design explanation - Further research: Compare the original protocol and amendment history to verify why both boxes were checked, and reconcile the design actually implemented with its reporting. - Conditions for verification: Preserve the actual crossover report and the registry's Yes entries for both designs at their respective original locations. - Why this condition is needed: Needed to avoid hiding the conflicting registry labels or arbitrarily changing the actually reported design to a parallel trial. - Application exceptions: Do not reassess conflicting registry checkboxes as errors in all RI numbers or as absence of random allocation. - Remaining 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. - Referenced methods: 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. - Related sources: S01, S02, S03 ### N09 · Have random sequence generation and allocation concealment been verified? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: The design label is available, but the necessary allocation details are not retained. - Reason for missing information: Generation algorithm, concealment procedures, allocation implementation and baseline balance unverified. - Required materials and conditions: Information on sequence generation, allocation concealment and actual baseline balance by sequence - Materials to obtain first: Information on sequence generation, allocation concealment and actual baseline balance by sequence - Further research: Propose a comparison that prespecifies sequence-generation and concealment procedures and baseline balance and discloses their actual implementation. - Conditions for verification: Record the allocation label and the verified scope of actual sequence generation, concealment and balance. - Why this condition is needed: Because the labels randomized and double-blind alone do not establish that allocation issues were resolved. - Application exceptions: The crossover/pilot label does not establish detailed generation, concealment or baseline balance, or completion of a formal RoB assessment. - Remaining uncertainty: Unverified details differ from proof of a flaw or certification of no bias. - Referenced methods: 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. - Related sources: S01, S02 ### N10 · Have the 34 completers been distinguished from the randomized count and number of analyzed RI pairs? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: Only the completion stage is established; analysis denominators and the boundaries of attrition require further verification. - Reason for missing information: Allocated count, number of people by sequence, paired RI denominator and exclusion flow unverified. - Required materials and conditions: CONSORT/crossover flow, allocation/completion/measurement by sequence and number of paired RI analyses - Materials to obtain first: CONSORT/crossover flow, allocation/completion/measurement by sequence and number of paired RI analyses - Further research: Propose reporting participant flow and paired denominators for each endpoint, with differences between allocation, completion and analysis disclosed. - Conditions for verification: Link completion, allocation, sequence, measurement and analysis to the denominator at each stage. - Why this condition is needed: Needed to avoid counting the same person's two periods as independent people or turning completers into a confirmed analysis denominator. - Application exceptions: 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. - Remaining uncertainty: The 34 completers cannot be used as n for every outcome or as the number in a complete paired analysis. - Referenced methods: 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. - Related sources: S01, S02 ### N11 · Can the handling of attrition/missing data and the ITT/PP analysis populations be established? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: Losses after allocation and the analysis definition cannot be established from the retained inputs read. - Reason for missing information: ITT/PP, missing paired data, reasons for attrition and handling of exclusions/imputation unverified. - Required materials and conditions: Data on allocation/attrition, reasons for missingness, definitions of analysis populations and sensitivity analyses - Materials to obtain first: Data on allocation/attrition, reasons for missingness, definitions of analysis populations and sensitivity analyses - Further research: Prespecify the effect of interest and analysis population, and plan sensitivity analyses that account for missing crossover data. - Conditions for verification: Link the verified scope of the actual analysis population, missing-data handling and attrition by sequence to the effect of interest. - Why this condition is needed: Needed to avoid automatically concluding from the completer count that only completers were analyzed. - Application exceptions: Do not arbitrarily label the completer report as complete-case, ITT or PP, or describe the information as unreported throughout the unread full text. - Remaining uncertainty: An information gap does not establish absence of missing data or the actual magnitude of bias. - Referenced methods: 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. - Related sources: S01, S02, S06, S07 ### N12 · Can it be established whether the 2-week washout excluded carryover? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: Information needed to verify actual residual/carryover effects on the selected RI comparison remains outstanding. - Reason for missing information: Rationale for washout, baseline recovery, carryover estimation/handling and residual exposure unverified. - Required materials and conditions: Crossover protocol, baseline/exposure by period and information on carryover assessment and handling - Materials to obtain first: Crossover protocol, baseline/exposure by period and information on carryover assessment and handling - Further research: Prespecify the rationale for washout and baseline measurements by period, and plan a crossover analysis that examines residual/carryover effects. - Conditions for verification: Distinguish the washout report from direct information on carryover assessment/handling and restoration of baseline in each period. - Why this condition is needed: Because residual effects of the previous treatment may be mixed with RI in the next period. - Application exceptions: Do not conclude from the nominal 2-week washout alone that there was no carryover or that washout was sufficient. - Remaining uncertainty: Do not conclude from the carryover gap that carryover actually occurred or that the crossover trial is invalid. - Referenced methods: 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. - Related sources: S01, S02, S06 ### N13 · Were sequence and period effects handled in the actual RI analysis? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: The currently retained methods do not contain the actual sequence/period model or its results. - Reason for missing information: Tables by sequence, period terms, changes by period and handling of interactions/modeling unverified. - Required materials and conditions: RI, baseline/medications, interactions and analysis model by sequence/period - Materials to obtain first: RI, baseline/medications, interactions and analysis model by sequence/period - Further research: Prespecify the treatment, period and sequence terms of interest and disclose sequence-specific data and sensitivity analyses. - Conditions for verification: Link sequence/period-specific data to the model's effect of interest and its handling. - Why this condition is needed: Because calendar time/period and allocation sequence can affect treatment differences even in before-and-after observations of the same person. - Application exceptions: Do not state that sequence and period effects were automatically removed because the participants were the same. - Remaining uncertainty: Unverified information does not establish the actual magnitude of period effects or how much they are mixed with treatment effects. - Referenced methods: 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. - Related sources: S01, S02, S06 ### N14 · Can the adjusted paired RI effect and the actual choice of test be established? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: A comparison P value is reported, but the actual estimation/test definition cannot be established. - Reason for missing information: Paired covariance, effect model, test type, degrees of freedom and effect of interest unverified. - Required materials and conditions: RI analysis plan, paired source data/covariance, adjusted model, test type and effect estimator - Materials to obtain first: RI analysis plan, paired source data/covariance, adjusted model, test type and effect estimator - Further research: Propose an analysis that prespecifies the paired effect of interest and period/sequence adjustment and reports that effect and its interval. - Conditions for verification: Retain the verified scope of the effect of interest, analysis population, pairing/covariance and actual test definition. - Why this condition is needed: Because a descriptive difference between two summary values differs from the actual paired causal estimate and test statistic. - Application exceptions: Do not back-calculate the outcome-specific ANOVA/Friedman choice, covariance or degrees of freedom from P=.63. - Remaining uncertainty: Do not create new SE/CI or causal effects using an independent two-group formula or back-calculation from the P value. - Referenced methods: 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. - Related sources: S01, S02 ### N15 · Have salbutamol RI measurement timing, sign convention and assessor blinding been verified? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: The type of physiological function test is verified, but measurement details and the dimensions needed to interpret a favorable direction remain unresolved. - Reason for missing information: Salbutamol challenge details, timing after measurement, sign convention, baseline RI and operator blinding unverified. - Required materials and conditions: Measurement protocol, challenge dose/time afterward, sign convention, baseline RI and operator-blinding/quality information - Materials to obtain first: Measurement protocol, challenge dose/time afterward, sign convention, baseline RI and operator-blinding/quality information - Further research: Propose a method that standardizes the RI challenge, collection time, sign convention and assessor blinding and reports baseline/reproducibility data. - Conditions for verification: Record the actual digital photoplethysmography/inhalation-challenge method and the remaining measurement dimensions. - Why this condition is needed: Because post-challenge timing, sign convention and assessment conditions may change interpretation even when the measure has the same name. - Application exceptions: Do not arbitrarily fill in operator blinding, challenge dose/timing or directional sign convention from the double-blind label. - Remaining uncertainty: The sign of −1.5 alone cannot establish whether vascular function improved or worsened. - Referenced methods: 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. - Related sources: S01, S02 ### N16 · Has digital RI been distinguished from FMD and prevention of clinical events? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: The manuscript's boundaries for selected and excluded endpoints have been accurately linked, without establishing clinical-event benefit. - Reason for missing information: Long-term clinical-event, quality-of-life and direct FMD data have not been acquired as answers to the current question. - Required materials and conditions: Measurement definition and separate direct results for claims about event prevention/quality of life - Materials to obtain first: Measurement definition and separate direct results for claims about event prevention/quality of life - Further research: If a clinical-event question is requested, address it through a study with a separate protocol, follow-up and event adjudication. - Conditions for verification: Identify the distinct questions concerning RI, brachial artery FMD, VCAM-1, TDP and clinical events. - Why this condition is needed: Needed to avoid automatically translating the selected functional response into other vascular measures or long-term events. - Application exceptions: Do not mechanically require cardiovascular-event trials merely to preserve observations for the RI question itself; extension to event prevention remains separately unverified. - Remaining uncertainty: Nonsignificance of the RI result neither refutes nor establishes FMD or event prevention. - Referenced methods: 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. - Related sources: S01, S02 ### N17 · Have the two reported RI values and P=0.63 been attributed to the original time point? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: 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. - Reason for missing information: Original units, SD/SE, baseline/change definition and adjusted-analysis details unverified. - Required materials and conditions: P72 RI result sentence, original table/units, explanation of variance and analysis location - Materials to obtain first: P72 RI result sentence, original table/units, explanation of variance and analysis location - Further research: Check the original results table to compare definitions of summary statistics, and specify units, variance and effect estimates in subsequent reporting. - Conditions for verification: Retain the reported values, 8-week RI and original P together with the gaps in units/variance. - Why this condition is needed: Needed to avoid deleting favorable or nonsignificant results or transferring them as values for another functional endpoint. - Application exceptions: Do not arbitrarily assign the type of ± value, absolute change or percentage to 5.3±9.2/6.8±6.9. - Remaining uncertainty: Retain the nonsignificant values without converting them into an effect of 0, equivalence or FMD numbers. - Referenced methods: 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. - Related sources: S01, S02 ### N18 · Have the original RI units and whether the ± values are SD or SE been verified? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: Although direct numbers are available, the current inputs contain no original explanation establishing their units or variance type. - Reason for missing information: Original RI units, SD/SE/other variance measure and paired covariance unverified. - Required materials and conditions: RI units, explanation of summary statistics, SD/SE, paired covariance and denominator data - Materials to obtain first: RI units, explanation of summary statistics, SD/SE, paired covariance and denominator data - Further research: Propose reporting the RI units, variance type and number of analyzed pairs explicitly, with intervals appropriate to the paired structure. - Conditions for verification: Clearly retain the absence of an original location providing the units/variance type. - Why this condition is needed: Needed to avoid creating a CI, percentage points or causal estimate from ± values of unknown type. - Application exceptions: Do not supplement a report lacking units with FMD %, absolute percentage points or relative percentage change. - Remaining uncertainty: This gap in the available information is not a new judgment that the reported numbers are erroneous and does not authorize interval recalculation. - Referenced methods: 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. - Related sources: S02 ### N19 · Has the existing difference of −1.5 been distinguished from an adjusted paired causal estimate? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: The identity and interpretive limitations of the existing descriptive value have been accurately preserved. - Reason for missing information: The exact adjusted estimator, SE/df/CI and paired covariance are separately unverified. - Required materials and conditions: Source location of the existing calculation, effect of interest and actual adjusted paired-estimate data - Materials to obtain first: Source location of the existing calculation, effect of interest and actual adjusted paired-estimate data - Further research: If the original analysis is acquired, report the descriptive summary difference separately from the prespecified paired effect of interest. - Conditions for verification: Record the historical calculation location for −1.5 together with its descriptive nature and unit limitations. - Why this condition is needed: Because a simple difference between two reported values is not guaranteed to equal the actual crossover trial's effect of interest. - Application exceptions: Only cite the existing calculation record; perform no new arithmetic, paired CI/SE calculation or FMD conversion in this work. - Remaining uncertainty: A Met status for preserving the descriptive value does not establish a causal treatment effect or the direction of benefit. - Referenced methods: 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. - Related sources: S02 ### N20 · Has P=0.63 been distinguished from a benefit of 0, equivalence or exclusion of important benefit? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: The original result has been retained, together with the boundary between nonsignificance and separate clinical/equivalence conclusions. - Reason for missing information: CI, MCID, prespecified equivalence margin and the corresponding test are unverified. - Required materials and conditions: Direct RI effect interval, justified importance/equivalence criteria and testing plan - Materials to obtain first: Direct RI effect interval, justified importance/equivalence criteria and testing plan - Further research: If equivalence or exclusion of important benefit is the question, plan separate verification with prespecified criteria, an effect of interest and adequate precision. - Conditions for verification: Identify the significance information provided by P and the different evidence required to judge no effect, equivalence and importance. - Why this condition is needed: Because a nonsignificant comparison in a small pilot trial alone cannot establish an exactly null effect or equivalence. - Application exceptions: 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. - Remaining uncertainty: The magnitude of possible remaining benefit or of effects excluded cannot be established. - Referenced methods: 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. - Related sources: S01, S02 ### N21 · Can the direct RI CI and an important difference be established? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: The direct effect interval and basis for clinical importance are currently unavailable, so interpretation of magnitude cannot be completed. - Reason for missing information: CI for the effect of interest, confidence level and MCID/validity evidence unverified. - Required materials and conditions: RI effect/CI, confidence level, variance, denominator and validated criteria for clinical importance - Materials to obtain first: RI effect/CI, confidence level, variance, denominator and validated criteria for clinical importance - Further research: First define the RI effect of interest and the basis for importance, then design the required precision to match that basis. - Conditions for verification: Explain the relationship between the interval for the actual effect of interest and justified evidence of importance, or why interpretation is not possible. - Why this condition is needed: Because precision/clinical importance cannot be determined from the number of completers or trial families alone. - Application exceptions: Do not adopt a common minimum participant count, duration or arbitrary MCID; retain unverified intervals/criteria. - Remaining uncertainty: The current CX is the historical handling in the original verdict; this row assigns no new grade or precision score. - Referenced methods: 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. - Related sources: S02 ### N22 · Have the registered primary (1st) VCAM-1 endpoint and the prespecified rank/analysis of RI been distinguished? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: The registered primary (1st) endpoint can be distinguished from the reported RI, but a complete comparison of prespecified analyses and rankings remains outstanding. - Reason for missing information: Full protocol/SAP, RI rank, multiple comparisons and reasons for changes unverified. - Required materials and conditions: Full registration/protocol, SAP, prespecified RI rank and multiple-comparison/amendment history - Materials to obtain first: Full registration/protocol, SAP, prespecified RI rank and multiple-comparison/amendment history - Further research: Propose subsequent reporting that prespecifies the RI of interest, time point and model and discloses reasons for changes and all endpoints. - Conditions for verification: Indicate the extent of comparison between registered endpoints and the original RI report, and reasons for multiple comparisons/changes. - Why this condition is needed: Needed to avoid promoting the page's functional endpoint to the registered primary (1st) endpoint or to a significant secondary (2nd) success. - Application exceptions: Do not change the registered primary (1st) endpoint or use the unverified prespecified RI rank/SAP as proof of selective reporting. - Remaining uncertainty: A verification gap is neither proof of selective reporting nor certification of its absence. - Referenced methods: 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. - Related sources: S02, S03, S06, S07 ### N23 · Have the registered schedule of 1 time per 1 day and the actual daily total/meal timing been distinguished? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: The plan and reported total are available, but checking actual implementation of the schedule/meal conditions remains outstanding. - Reason for missing information: Actual 1-time schedule, meal/fasting conditions and dosing diaries unverified. - Required materials and conditions: Actual administration times/frequency, meal conditions, dosing diaries and plan-change information - Materials to obtain first: Actual administration times/frequency, meal conditions, dosing diaries and plan-change information - Further research: Record actual administration and meal conditions and prespecify how changes/deviations from the plan will be handled. - Conditions for verification: Separate the verification levels of the reported total, registered plan and actual schedule/meal conditions. - Why this condition is needed: Because a planned schedule does not guarantee actual administration frequency, meal conditions or adherence implementation. - Application exceptions: 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. - Remaining uncertainty: These items have different levels of verification; no new determination is made that an actual protocol deviation occurred. - Referenced methods: 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. - Related sources: S01, S03, S05, S18 ### N24 · Does an increase in blood TDP establish individual adherence or RI benefit? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: The context of an increased exposure marker is available, but individual implementation and contribution to function remain separate gaps. - Reason for missing information: Individual amounts actually taken, dosing/deviations by period and exact exposure values unverified. - Required materials and conditions: Data on individual intake, exposure/TDP by period and handling of treatment deviations - Materials to obtain first: Data on individual intake, exposure/TDP by period and handling of treatment deviations - Further research: Collect adherence records and exposure markers separately from the RI effect of interest, and prespecify how deviations will be handled. - Conditions for verification: Distinguish the existence of an increased exposure marker from individual adherence, deviations by period and functional outcomes. - Why this condition is needed: Because biochemical exposure, individual dosing adherence and functional benefit are different outcomes. - Application exceptions: Do not add new exact numbers to the retained TDP increase or convert it into adherence by all participants, baseline deficiency or RI efficacy. - Remaining uncertainty: An exposure marker cannot be used as clinical surrogate validation or automatic proof of functional benefit. - Referenced methods: 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. - Related sources: S01, S02 ### N25 · Have the thesis, P72, registration/ethics records and mirror been linked as the same F01? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: The strong documentary identity linkage for the same trial and the rules preventing duplication have been retained. - Reason for missing information: Cohort comparison at the individual-identifier level and the number of analyzed RI pairs are unverified. - Required materials and conditions: Identity linkage across reports, registrations and ethics/trial records, cohort overlap and original locations for each endpoint - Materials to obtain first: Identity linkage across reports, registrations and ethics/trial records, cohort overlap and original locations for each endpoint - Further research: Propose a subsequent review that maintains a family table and an endpoint/time-point/analysis linkage table centered on the original trial. - Conditions for verification: Preserve the evidence linking documents in the same family and the original record of 1 direct family and 34 completers. - Why this condition is needed: Needed to avoid counting multiple reports of the same trial as independent replications or duplicated participant populations. - Application exceptions: This is a documentary comparison linking authors, institution, regimen/duration, the 34 completers and registered title, not verification at the level of individual identifiers. - Remaining uncertainty: Matching document identities is not independent external clinical certification or proof that a confirmatory trial was conducted. - Referenced methods: 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. - Related sources: S01, S02, S03, S04, S05, S06, S07, S08, S18 ### N26 · Can between-study heterogeneity be estimated from the single verified direct family? Verification status: Not applicable Reading scope: 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 - Current findings: 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. - Why unverified: 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. - Reason for missing information: Additional independent direct RI results and the distribution of their conditions have not yet been acquired. - Required materials and conditions: Results, populations, dose/duration and analysis information for additional independent direct RI families - Materials to obtain first: Results, populations, dose/duration and analysis information for additional independent direct RI families - Further research: If a new direct family is acquired, separate its conditions and results and compare them according to prespecified heterogeneity hypotheses. - Conditions for verification: Specify when comparisons between families apply and the manuscript's scope of a single direct family. - Why this condition is needed: Needed to avoid presenting multiple reports of the same trial as between-study consistency or replicated effects. - Application exceptions: 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. - Remaining uncertainty: Nonapplicability within the current scope is not an exhaustive guarantee of study absence, sufficient replication or absence of inconsistency. - Referenced methods: 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. - Related sources: S01, S02, S19 ### N27 · Have the two registered completion dates and the results posting date been distinguished? Verification status: Conflicting information Reading scope: 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 - Current findings: 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. - Why unverified: The completion dates differ between the two registry records, and their definitions/reasons for change have not been verified. - Reason for missing information: Completion definitions, registry history, the body of the end-of-study attachment and the reason for the date difference are unverified. - Required materials and conditions: Registry amendment history, definitions of completion dates, end-of-study report and posted-version information - Materials to obtain first: Registry amendment history, definitions of completion dates, end-of-study report and posted-version information - Further 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. - Conditions for verification: Preserve the completion dates in protocol/results metadata and the posting event in 2019 separately. - Why this condition is needed: Needed to avoid hiding differences in registry calendar dates or using the results posting date as the end of treatment. - Application exceptions: Do not turn the difference between 2011-07-04/2011-07-31 into an error in the nominal 8-week treatment period. - Remaining uncertainty: Do not automatically expand different calendar events into a conflict about the nominal 8-week duration, RI measurement timing or clinical results. - Referenced methods: 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. - Related sources: S03, S04, S07 ### N28 · Have both HRA's n/a and the original registry's ISRCTN linkage been retained? Verification status: Conflicting information Reading scope: 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 - Current findings: 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. - Why unverified: The same-trial identity linkage has been retained together with the discrepancy in the ISRCTN field. - Reason for missing information: The reason for the identifier-entry change and the S08 original record text/full history are unverified. - Required materials and conditions: Ethics/registry identifier amendment history, original ISRCTN record and explanation linking the same trial - Materials to obtain first: Ethics/registry identifier amendment history, original ISRCTN record and explanation linking the same trial - Further research: Maintain a common trial identity table and compare the original registry/ethics history for the reason behind the different identifier entries. - Conditions for verification: Distinguish the original registered identifier, the different ethics-record entry and the unacquired ISRCTN record text. - Why this condition is needed: Needed to avoid hiding differences between identifier fields or claiming to have read the ISRCTN record text. - Application exceptions: 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. - Remaining uncertainty: n/a or a holding page does not establish absence of a trial identity, current deletion or nonregistration. - Referenced methods: 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. - Related sources: S03, S05, S08 ### N29 · Have reading the summaries and currently not reading the 21 external sources been separated? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: Historical access successes/failures have been distinguished from current reading of retained summaries and recorded for each report and material type. - Reason for missing information: 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. - Required materials and conditions: Records of exact locations in the retained inputs, material types/access, reading/byte hashes and dates - Materials to obtain first: Records of exact locations in the retained inputs, material types/access, reading/byte hashes and dates - Further 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. - Conditions for verification: Record exact retained source-summary pointers/hashes, current access/acquisition/reading by material type and historical dates separately. - Why this condition is needed: Needed to avoid promoting historical reading of abstracts, P72, registration/product information into direct reading in this work. - Application exceptions: Existence of a link/DOI is not full-text reading. Do not label access not attempted in this work as Inaccessible. - Remaining uncertainty: The SHA of a retained source summary is not the SHA of the external PDF/registry binary. - Referenced methods: 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. - Related sources: S01, S02, S03, S04, S05, S06, S07, S08, S09, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21 ### N30 · Can methods and original results in the full thesis and end-of-study attachment be compared? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: 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. - Reason for missing information: Full methods, original RI tables, denominators, allocation/analysis/SAP and trial safety tables are unverified. - Required materials and conditions: Full thesis, end-of-study report attachment, original RI tables/methods and appendix/analysis/safety data - Materials to obtain first: Full thesis, end-of-study report attachment, original RI tables/methods and appendix/analysis/safety data - Further 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. - Conditions for verification: Record the scope of reports read at the time and content gaps in major original full texts that were not accessed. - Why this condition is needed: Because the institutional abstract and complete P72 conference abstract do not replace the full trial report. - Application exceptions: 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. - Remaining uncertainty: Do not reinterpret access failures at that time as current network failures or nonreporting throughout the article. - Referenced methods: 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. - Related sources: S01, S02, S06, S07 ### N31 · Has transfer of the acute intravenous BAVA in S09 to oral 8-week RI been avoided? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: The adjacent evidence has been separated from the selected RI result based on the currently retained differences in route/measure. - Reason for missing information: The acute experiment's full methods/specific values and a direct link to single-ingredient oral RI are unverified. - Required materials and conditions: Actual route, challenge conditions, BAVA definition and original methods in S09 - Materials to obtain first: Actual route, challenge conditions, BAVA definition and original methods in S09 - Further research: If an intravenous challenge-function question is requested, review it using a separate route/measure protocol and population. - Conditions for verification: Preserve only the adjacent evidence's route/measure differences and reasons for exclusion. - Why this condition is needed: Needed to avoid merging evidence with the same thiamine name but different routes, challenge conditions and measures as independent replications of oral RI. - Application exceptions: In S09, the blood-flow augmentation with 100 mg intravenous thiamine after glucose challenge is neither brachial diameter FMD nor an oral RI effect. - Remaining uncertainty: Exclusion of the adjacent study is not a new negative efficacy judgment for S09. - Referenced methods: 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. - Related sources: S09 ### N32 · Has use of the dietary thiamine association in S10 as a single-ingredient causal effect been avoided? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: The actual differences in exposure/design are recorded, and the observational association has not been transferred into a causal treatment effect. - Reason for missing information: The original observation's full analyses, adjustment/timing data and the direct oral RI effect remain separate gaps. - Required materials and conditions: The dietary study's exposure, population, adjustment/timing and whether an actual treatment comparison exists - Materials to obtain first: The dietary study's exposure, population, adjustment/timing and whether an actual treatment comparison exists - Further research: Address dietary associations through separate prospective observation and supplementation efficacy alone through comparisons with matched background treatment. - Conditions for verification: Indicate the actual scope of exclusion based on observational design, dietary exposure and absence of a treatment comparison. - Why this condition is needed: Because dietary intake/status associations differ in exposure direction and design from randomized comparisons of additional supplementation. - Application exceptions: Do not extract the incremental effect of single-ingredient oral 300 mg/day from dietary associations with EPC/endothelial function. - Remaining uncertainty: Separating S10 from direct efficacy does not establish that the dietary association is null. - Referenced methods: 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. - Related sources: S10 ### N33 · Have benfotiamine FMD results been separated from ordinary-thiamine RI? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: Different active ingredients, challenge conditions and reading levels have been preserved without adding them as direct replications. - Reason for missing information: Their respective full methods, derivative contributions/original tables and the current direct RI result for ordinary thiamine are separate. - Required materials and conditions: Original ingredient, route, FMD/challenge conditions and identity of original results for each derivative - Materials to obtain first: Original ingredient, route, FMD/challenge conditions and identity of original results for each derivative - Further research: Design/review derivative questions using separate ingredients and measures, and distinguish them from the current ordinary-thiamine RI family. - Conditions for verification: Record differences in active ingredients, challenge populations and measures, together with the actual access level for each material. - Why this condition is needed: Needed to avoid using data for different active molecules or smoking/meal challenge conditions as replications of the ordinary thiamine hydrochloride trial. - Application exceptions: 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. - Remaining uncertainty: This exclusion is neither a new reassessment of derivative efficacy nor proof of no effect. - Referenced methods: 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. - Related sources: S11, S12, S13 ### N34 · Has use of the combination products in S14/S15 as a direct effect of adding B1 been avoided? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: Differences in combinations, populations and designs have been separated from gaps in report lineage. - Reason for missing information: The S15 full text, family relationship with earlier reports and isolated B1 contribution within the combination are unverified. - Required materials and conditions: Combination-product ingredients/populations, comparisons, report lineage/funding and actual evidence of the isolated contribution - Materials to obtain first: Combination-product ingredients/populations, comparisons, report lineage/funding and actual evidence of the isolated contribution - Further research: Keep combination products as separate questions; if the isolated contribution is asked about, propose a component comparison with matched background ingredients. - Conditions for verification: Indicate combined ingredients, population/design, access level and gaps concerning possible overlap. - Why this condition is needed: Because results involving multiple active ingredients and uncontrolled/healthy populations are not comparisons of thiamine alone in high-risk diabetes. - Application exceptions: Attribute Valerio's interests only to that family, and do not count the unclear link between S15 and earlier reports as independent replication. - Remaining uncertainty: Do not assume that different combination products are equivalent independent replications or transfer their funding to F01. - Referenced methods: 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. - Related sources: S14, S15 ### N35 · Has use of the S18 mirror and S20/S21 reviews as original-trial numbers/funding been avoided? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: The attribution boundary between original materials and secondary (2nd) discovery information has been retained. - Reason for missing information: The full S20 page, original-trial funding/methods, review inclusion tables and disclosure linkages are unverified. - Required materials and conditions: Original trial/registration funding, measurement methods/dates and linkage tables for studies/families included in reviews - Materials to obtain first: Original trial/registration funding, measurement methods/dates and linkage tables for studies/families included in reviews - Further research: Limit discovery materials to maps for tracing original trials, and compare original funding, methods and results separately. - Conditions for verification: Link the information levels of original registrations/trials and secondary (2nd) discovery materials. - Why this condition is needed: Because discovery maps and disclosure excerpts do not replace direct verification of original-trial results/funding. - Application exceptions: 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. - Remaining 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. - Referenced methods: 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. - Related sources: S18, S20, S21 ### N36 · Can the registered ingredient, status and results of NCT06322212 be established? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: The candidate registry content has not been read, so the actual ingredient/results and current status cannot be established. - Reason for missing information: Original registry content, current status, formulation, endpoints and results/family relationships are unverified. - Required materials and conditions: Original NCT06322212 registry record, amendment history, ingredient/population, endpoints and actual results - Materials to obtain first: Original NCT06322212 registry record, amendment history, ingredient/population, endpoints and actual results - Further research: Propose a subsequent review that first acquires the permitted official registry record and compares eligibility for the question and reported results. - Conditions for verification: Separate candidate identity from gaps in actual content and mark current access as not attempted. - Why this condition is needed: Needed to avoid inventing recruitment/formulation/numbers from an empty app screen or silently excluding the candidate. - Application exceptions: Do not establish current status, lack of posting or trial eligibility for a candidate for which only an HTML shell was seen previously. - Remaining uncertainty: An unverified candidate does not establish ineligibility, study absence or current lack of posting. - Referenced methods: 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. - Related sources: S19 ### N37 · Have a noncommercial sponsor and trial-specific funding, product supply and COI been distinguished? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: Sponsor identity or mirror/review excerpts cannot establish trial-specific funding or independence. - Reason for missing information: Original-trial funding, product supply, author COI and sponsor roles are unverified. - Required materials and conditions: Declarations of trial funding, product supply, author employment/disclosed COI and sponsor roles - Materials to obtain first: Declarations of trial funding, product supply, author employment/disclosed COI and sponsor roles - Further research: Disclose funding, product supply and analysis/publication roles in subsequent trials, and verify independent replication separately. - Conditions for verification: Link what is verified about the sponsor to the unverified trial-specific funding and product/author relationships. - Why this condition is needed: Needed to avoid converting unverified funding into confirmed independent/mixed funding or absence of bias. - Application exceptions: 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. - Remaining uncertainty: A funding gap is not a new judgment that commercial/mixed funding exists or that results are invalid. - Referenced methods: 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. - Related sources: S01, S02, S03, S18, S21 ### N38 · Has transfer of the S16 product/route cautions to actual trial risks been avoided? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: 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. - Reason for missing information: Cautions for the exact Tyvera product/batch, trial GI/hypersensitivity occurrence and denominators/durations are unverified. - Required materials and conditions: Exact trial-product information, GI/hypersensitivity events by period, collection/denominators and route information - Materials to obtain first: Exact trial-product information, GI/hypersensitivity events by period, collection/denominators and route information - Further research: Systematically collect harms for the exact product/route and report official cautions separately from trial observations. - Conditions for verification: Record the information level of official oral gastrointestinal/hypersensitivity cautions and the limits of applicability by product and route. - Why this condition is needed: Because official cautions for a different product and era differ from events/frequencies observed in the trial. - Application exceptions: Flamingo 100 mg product information does not describe the actual Tyvera batch. Do not convert the predominantly parenteral hypersensitivity context into oral incidence. - Remaining uncertainty: Official cautions are not causal risk estimates from the actual trial, oral incidence or a new safety grade. - Referenced methods: 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. - Related sources: S16 ### N39 · Has use of an unestablished UL and medication cautions as unlimited safety/efficacy been avoided? Verification status: Partly verified Reading scope: 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 - Current findings: 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. - Why unverified: The scope of general safety information is retained, but direct data on the exact regimen and concomitant treatments remain outstanding. - Reason for missing information: Interactions with specific concomitant treatments, rare/long-term risks and exposure denominators in the high-risk population are unverified. - Required materials and conditions: Updates to official source information, exact concomitant medications/exposure and safety data by baseline risk - Materials to obtain first: Updates to official source information, exact concomitant medications/exposure and safety data by baseline risk - Further research: Design a safety study that records exact concomitant treatments and exposure, and separately compare the applicability of general information. - Conditions for verification: Separate the UL/medication context in general thiamine information from the unverified exact population and regimen. - Why this condition is needed: Because an unestablished upper limit and general medication context do not guarantee safety testing or benefit for the exact high-risk regimen. - Application exceptions: 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. - Remaining uncertainty: Absence of a UL is not evidence of high-dose harmlessness, no interactions or authorization for personal dosing. - Referenced methods: 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. - Related sources: S17 ### N40 · Can event/person counts and discontinuation denominators be established for each crossover period? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: The selected regimen's actual harms tables and denominators/collection by period cannot be established from the current inputs. - Reason for missing information: Event/person counts, exposure time, collection by period and reasons for discontinuation/losses are unverified. - Required materials and conditions: Exposure denominators, event/person counts such as GI/hypersensitivity events, discontinuations/serious events and collection/loss tables for each treatment period - Materials to obtain first: Exposure denominators, event/person counts such as GI/hypersensitivity events, discontinuations/serious events and collection/loss tables for each treatment period - Further research: Systematically collect prespecified harms while distinguishing exposure by crossover period, recurrent events/person counts and reasons for discontinuation. - Conditions for verification: Link exposure by period, event/person counts, severity/reasons for discontinuation and collection/missingness. - Why this condition is needed: Because the number of trial completers differs from harm collection/event frequency. - Application exceptions: Do not convert efficacy grade D, the 34 completers or the existence of general product information into 0 events, 0 discontinuations or NNH. - Remaining uncertainty: Unverified harms do not establish absence of events or safety, and do not erase the RI observations themselves. - Referenced methods: 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. - Related sources: S01, S02, S07, S16, S17 ### N41 · Can 8-week RI be extended to long-term persistence, optimal doses or special populations? Verification status: Unverified Reading scope: 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 - Current findings: 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. - Why unverified: Direct estimates/safety data for extensions beyond the selected short-term outcome have not been established. - Reason for missing information: Long-term/post-discontinuation outcomes, dose comparisons, prespecified subgroups and efficacy/safety in special populations are unverified. - Required materials and conditions: Post-discontinuation/long-term RI, direct dose comparisons, interactions with baseline status/special populations and long-term safety - Materials to obtain first: Post-discontinuation/long-term RI, direct dose comparisons, interactions with baseline status/special populations and long-term safety - Further research: Plan long-term, dose and subgroup questions as separate prespecified comparative/follow-up studies and distinguish them from the current result. - Conditions for verification: Indicate separately the defined original duration and gaps in direct estimates/safety for extensions. - Why this condition is needed: Needed to avoid transferring the narrow short-term functional result to long-term efficacy/safety, special populations or dose optimization. - Application exceptions: Do not mechanically require every long-term/event/subgroup trial for the 8-week RI observation; extension questions require separate evidence. - Remaining uncertainty: Gaps in extensions neither invalidate the current 8-week RI numbers nor guarantee identical efficacy across all extensions. - Referenced methods: 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. - Related sources: S01, S02, S16, S17 ### N42 · Has use of the 42 web searches and 3 failed attempts as current comprehensive verification been avoided? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: Historical searches/failures have been distinguished from the current review scope, and statements of absence have been bounded. - Reason for missing information: Current comprehensive database coverage, all unpublished materials and the latest correction/retraction/candidate statuses are unverified. - Required materials and conditions: Records of the historical search/access scope and verification of unpublished materials/candidates and correction/retraction/publication status - Materials to obtain first: Records of the historical search/access scope and verification of unpublished materials/candidates and correction/retraction/publication status - Further research: In an explicitly permitted subsequent update, record search sources, queries, inaccessible/negative materials and corrections/retractions by date. - Conditions for verification: Specify the evidence cutoff, actual review date, historical search/access limitations and scope of correction/retraction updates. - Why this condition is needed: 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 exceptions: 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. - Remaining uncertainty: The 1 direct family is a record within this retained scope, not a definitive count of unique trials worldwide. - Referenced methods: 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. - Related sources: S01, S02, S19, S20, S21 ### N43 · Have D/28, the original axes and self-review been distinguished from a new table verdict or clinical certification? Verification status: Met Reading scope: 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 - Current findings: 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. - Why unverified: The original verdict, explanations of axes, self-review, canonical URL/publication history and boundaries of the current preparation have been linked. - Reason for missing information: No new original full-text verification, independent review, clinical reassessment or publication of the public table was performed. - Required materials and conditions: Current original verdict/axes, grading reasons, self-review/technical-publication history and canonical identity - Materials to obtain first: Current original verdict/axes, grading reasons, self-review/technical-publication history and canonical identity - Further 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. - Conditions for verification: Record the original D/28, Caution, historical handling/limitations of the axes, canonical URL and current local preparation scope. - Why this condition is needed: Because the original verdict/score, document quality and completion of the current table are different statuses. - Application exceptions: 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. - Remaining uncertainty: Meeting criteria or self-reviewing preparation does not raise/lower the original D/28 and Caution or create a new score. - Referenced methods: 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. - Related sources: S01, S02 ## Evidence and sources ### S01 Page GLJ. Oral thiamine supplementation in subjects with type 2 diabetes mellitus. MD thesis, December 2013. [Source](https://researchportal.port.ac.uk/en/studentTheses/oral-thiamine-vitamin-b1-supplementation-in-subjects-with-type-2-/) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: False | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Institutional thesis abstract webpage | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S02 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. [Source](https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dme.12091_1) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: False | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Conference abstract PDF | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Full trial report and original analysis/safety data | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S03 EU Clinical Trials Register protocol, 2009-017537-21, GB [Source](https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/GB) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: False | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full official registry web text | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Protocol, analysis plan and registry amendment history | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S04 EU Clinical Trials Register results metadata, 2009-017537-21 [Source](https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/results) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: False | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Official results-metadata webpage | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | End-of-study report attachment | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S05 UK HRA: Thiamine supplementation in type 2 diabetes [Source](https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/thiamine-supplementation-in-type-2-diabetes/) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: False | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Ethics research-summary webpage | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S06 Page MD thesis full PDF, linked from university record [Source](https://researchportal.port.ac.uk/files/5949788/GPage_MD_for_printing.pdf) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: False | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full thesis PDF | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S07 Thiamine End of Study Report attachment [Source](https://www.clinicaltrialsregister.eu/ctr-search/rest/download/result/attachment/2009-017537-21/1/26416) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: False | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | End-of-study report attachment | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S08 ISRCTN30703970 trial record [Source](https://www.isrctn.com/ISRCTN30703970) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: False | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full official registry web text | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Registry amendment history and results/protocol | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S09 Arora et al. Thiamine improves endothelium-dependent vasodilatation in the presence of hyperglycemia. Ann Vasc Surg 2006;20:653–658. [Source](https://pure.johnshopkins.edu/en/publications/thiamine-vitamin-bsub1sub-improves-endothelium-dependent-vasodila/) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Institutional article-abstract webpage | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Original article full text and methods/source data | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S10 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. [Source](https://pubmed.ncbi.nlm.nih.gov/18925614/) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Article abstract | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Original article full text and methods/source data | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S11 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. [Source](https://pubmed.ncbi.nlm.nih.gov/23701274/) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Article abstract | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Original article full text and methods/source data | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S12 Benfotiamine counteracts smoking-induced vascular dysfunction in healthy smokers (2012) [Source](https://onlinelibrary.wiley.com/doi/pdf/10.1155/2012/968761) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Article title and index excerpt | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Original article full web text | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S13 Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products (2006) [Source](https://diabetesjournals.org/care/article/29/9/2064/24125/Benfotiamine-Prevents-Macro-and-Microvascular) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Article title and index excerpt | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Original article full web text | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S14 Valerio V et al. Oral nutraceutical intervention to improve endothelial function: Evidence from in vitro and pilot clinical studies. Biomed Pharmacother. 2025;191:118552. [Source](https://pubmed.ncbi.nlm.nih.gov/40957246/) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Article abstract | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Original article full web text and methods/source data | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S15 Antioxidant formulation preprint involving L-cysteine, thiamine hydrochloride, pyridoxine and ascorbic acid (2025) [Source](https://www.preprints.org/manuscript/202501.0355/v1/download) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Preprint index excerpt | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Full preprint PDF | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S16 Thiamine Hydrochloride 100 mg Tablets, Flamingo Pharma UK Ltd: Summary of Product Characteristics [Source](https://www.medicines.org.uk/emc/product/13528/smpc) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full official product-information web text | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Original harm data for the exact trial product and route | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S17 NIH Office of Dietary Supplements: Thiamin—Health Professional Fact Sheet [Source](https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full official fact-sheet web text | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Original safety data for the exact population, concomitant treatments and regimen | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S18 TrialScreen mirror for ISRCTN30703970 [Source](https://trialscreen.org/trials/phase-2-type-diabetes-mellitus-thiamine-supplementation-trial-isrctn30703970) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: False | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Registry-mirror index excerpt | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S19 ClinicalTrials.gov NCT06322212 [Source](https://clinicaltrials.gov/study/NCT06322212) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full official registry web text | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Registry amendment history and results/protocol | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S20 Serra et al. Thiamine/benfotiamine cardiovascular evidence review, IJMS 2025;26:3932 [Source](https://www.mdpi.com/1422-0067/26/9/3932) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Review index excerpt | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Review full web text and included-trial table | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ### S21 Page, Laight and Cummings review (2011) [Source](https://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2011.02680.x) Materials actually 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 Findings recorded in the summary: 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. Record level: Attribution summary of extraction/bibliographic/access records retained as of 2026-09-16; not verification of external results in this work Independent replication: None | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Review bibliographic/index excerpt | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | | Review full web text and included-trial table | Currently unverified (no external query in this work) | Access not attempted | Not read | 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. | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility criteria and reasons for changes, and distinguish variations in the intervention. · 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. - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish and link studies and reports, and do not omit a study solely because its outcomes are not reported. · 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. - M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting. · 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. - M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · 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. - M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Questions about harms may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence. · 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. ## What the statuses mean - 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. ## Change history 2026-11-07 · Public page/materials 1.0. Public-facing display and data were prepared from the existing 43 items. No new clinical search, verification-status change or scoring was performed. ## Material-specific source addresses - [S01-M1 · Institutional thesis abstract webpage](https://researchportal.port.ac.uk/en/studentTheses/oral-thiamine-vitamin-b1-supplementation-in-subjects-with-type-2-/) - [S02-M1 · Conference abstract PDF](https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dme.12091_1) - S02-M2 · Full trial report and original analysis/safety data: Material URL unverified; external material unread. - [S03-M1 · Full official registry web text](https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/GB) - [S03-M2 · Protocol, analysis plan and registry amendment history](https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/GB) - [S04-M1 · Official results-metadata webpage](https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-017537-21/results) - [S04-M2 · End-of-study report attachment](https://www.clinicaltrialsregister.eu/ctr-search/rest/download/result/attachment/2009-017537-21/1/26416) - [S05-M1 · Ethics research-summary webpage](https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/thiamine-supplementation-in-type-2-diabetes/) - [S06-M1 · Full thesis PDF](https://researchportal.port.ac.uk/files/5949788/GPage_MD_for_printing.pdf) - [S07-M1 · End-of-study report attachment](https://www.clinicaltrialsregister.eu/ctr-search/rest/download/result/attachment/2009-017537-21/1/26416) - [S08-M1 · Full official registry web text](https://www.isrctn.com/ISRCTN30703970) - [S08-M2 · Registry amendment history and results/protocol](https://www.isrctn.com/ISRCTN30703970) - [S09-M1 · Institutional article-abstract webpage](https://pure.johnshopkins.edu/en/publications/thiamine-vitamin-bsub1sub-improves-endothelium-dependent-vasodila/) - S09-M2 · Original article full text and methods/source data: Material URL unverified; external material unread. - [S10-M1 · Article abstract](https://pubmed.ncbi.nlm.nih.gov/18925614/) - S10-M2 · Original article full text and methods/source data: Material URL unverified; external material unread. - [S11-M1 · Article abstract](https://pubmed.ncbi.nlm.nih.gov/23701274/) - S11-M2 · Original article full text and methods/source data: Material URL unverified; external material unread. - [S12-M1 · Article title and index excerpt](https://onlinelibrary.wiley.com/doi/pdf/10.1155/2012/968761) - [S12-M2 · Original article full web text](https://onlinelibrary.wiley.com/doi/pdf/10.1155/2012/968761) - [S13-M1 · Article title and index excerpt](https://diabetesjournals.org/care/article/29/9/2064/24125/Benfotiamine-Prevents-Macro-and-Microvascular) - [S13-M2 · Original article full web text](https://diabetesjournals.org/care/article/29/9/2064/24125/Benfotiamine-Prevents-Macro-and-Microvascular) - [S14-M1 · Article abstract](https://pubmed.ncbi.nlm.nih.gov/40957246/) - S14-M2 · Original article full web text and methods/source data: Material URL unverified; external material unread. - [S15-M1 · Preprint index excerpt](https://www.preprints.org/manuscript/202501.0355/v1/download) - [S15-M2 · Full preprint PDF](https://www.preprints.org/manuscript/202501.0355/v1/download) - [S16-M1 · Full official product-information web text](https://www.medicines.org.uk/emc/product/13528/smpc) - S16-M2 · Original harm data for the exact trial product and route: Material URL unverified; external material unread. - [S17-M1 · Full official fact-sheet web text](https://ods.od.nih.gov/factsheets/Thiamin-HealthProfessional/) - S17-M2 · Original safety data for the exact population, concomitant treatments and regimen: Material URL unverified; external material unread. - [S18-M1 · Registry-mirror index excerpt](https://trialscreen.org/trials/phase-2-type-diabetes-mellitus-thiamine-supplementation-trial-isrctn30703970) - [S19-M1 · Full official registry web text](https://clinicaltrials.gov/study/NCT06322212) - [S19-M2 · Registry amendment history and results/protocol](https://clinicaltrials.gov/study/NCT06322212) - [S20-M1 · Review index excerpt](https://www.mdpi.com/1422-0067/26/9/3932) - [S20-M2 · Review full web text and included-trial table](https://www.mdpi.com/1422-0067/26/9/3932) - [S21-M1 · Review bibliographic/index excerpt](https://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2011.02680.x) - [S21-M2 · Review full web text and included-trial table](https://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2011.02680.x)