{ "schema_version": "chamgap-public-criteria-1.0", "title": "Ordinary thiamine (vitamin B1); actual salt not reported × Three-month Cockcroft–Gault-derived renal-function readout in early diabetic nephropathy", "criteria_version": "3121-ORAL-THIAMINE-CG-3M-1.0", "criteria_date": "2026-10-04", "condition_origin": "Chamgap application criteria", "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility criteria and reasons for changes, and distinguish variations in the intervention.", "review_level": "From 1585, reuse of the retained methodological principles/versions and actual HTML5 copies. This is not new reading of the full methodological texts or formal implementation/certification in the current work." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish and link studies and reports, and do not omit a study solely because its outcomes are not reported.", "review_level": "From 1585, reuse of the retained methodological principles/versions and actual HTML5 copies. This is not new reading of the full methodological texts or formal implementation/certification in the current work." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting.", "review_level": "From 1585, reuse of the retained methodological principles/versions and actual HTML5 copies. This is not new reading of the full methodological texts or formal implementation/certification in the current work." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "From 1585, reuse of the retained methodological principles/versions and actual HTML5 copies. This is not new reading of the full methodological texts or formal implementation/certification in the current work." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Questions about harms may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence.", "review_level": "From 1585, reuse of the retained methodological principles/versions and actual HTML5 copies. This is not new reading of the full methodological texts or formal implementation/certification in the current work." } ], "status_dictionary": { "Partly verified": "Some records are available, but gaps remain in actual exposure, population/comparator, denominators/intervals and original-source access.", "Unverified": "The necessary information/conditions cannot be established within the scope checked in the current work.", "Review incomplete": "Comparison/search of original materials was not performed within the authorized scope.", "Not reported": "A scope-limited status indicating that the item was not stated in the specific material/section read.", "Inaccessible": "Used only for materials where access was actually attempted and failed. Not assigned to clinical materials in the current work.", "Insufficient eligible evidence": "Used only when relevant studies within a defined scope have been reviewed and the evidence is insufficient to answer the conditions. Not applied exhaustively in the current work.", "Not applicable": "A specific exception under the applicability conditions. Not a substitute status for material that has not been read.", "Conflicting information": "An unresolved difference in dosage-form descriptions within the same trial. Differences in results from different analyses/measures are not automatically called conflicts.", "Met": "Verification of the specified preservation/distinction/linking conditions. This is not certification of clinical efficacy, reading of external full texts or individual safety.", "Does not apply": "A material/extension boundary that does not apply to the direct conditions of the current locked question. Direct evidence is required for the corresponding separate claim." }, "requirements": [ { "item_id": "N01", "question_type": "Independent claim", "question": "Which thiamine renal-function question is being presented in a single table?", "needed": "The current manuscript's boundaries for population, single active ingredient, oral route, placebo/usual care, and CG end mean at 3 months", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid combining renal-function values, urinary albumin, long-term progression and other preparations into a single efficacy status.", "application_exception": "Do not remove the unspecified CKD stage and unreported salt to present an apparently precise identity.", "criterion": "Retain the same independent question as the original /ko/effect and the actual PICO/time point, and explain the excluded questions.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Extract direct comparative results within this boundary, and keep eGFR slope and kidney-failure events as separate questions." }, { "item_id": "N02", "question_type": "Molecule and salt", "question": "Have the actual salt and equivalent amount of single-ingredient ordinary thiamine been verified?", "needed": "Trial product ingredient list, salt, purity, manufacturer, excipients and free-thiamine equivalent", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid treating ordinary thiamine, hydrochloride, nitrate, benfotiamine and a separate authorized product as the same exposure.", "application_exception": "Preserve the record of a single active ingredient, but do not fill in hydrochloride for the unreported salt.", "criterion": "Record the original trial's single active ingredient separately from the unverified chemical form/product identity.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Verify identity against the original product and manufacturing/ingredient records, and review other salts and derivatives separately." }, { "item_id": "N03", "question_type": "Physical dosage form", "question": "Has the difference between the capsule and tablet descriptions in the original article been resolved?", "needed": "Exact dosage-form wording in the S01 abstract and methods, and product/batch verification materials", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid silently harmonizing different dosage-form descriptions within the same original article.", "application_exception": "Do not infer a different trial or a difference in effects from the capsule/tablet discrepancy.", "criterion": "Preserve both descriptions and retain the conflict until verified against evidence about the actual product.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare the original article's dosage-form descriptions with product records to clarify the physical dosage form in the same trial." }, { "item_id": "N04", "question_type": "Nominal and actual dose", "question": "Have the nominal dose and the actual dosing schedule and adherence been distinguished?", "needed": "Nominal 3×100 mg/day; actual administration/intake records; meal timing; adherence rate; active-ingredient equivalent", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid automatically converting a nominal total amount into actual exposure or a schedule of 3 times a day.", "application_exception": "The retained 300 mg/day is an existing record, not a value calculated in the current work or a suggested dose for self-administration.", "criterion": "Preserve the original nominal amount, and indicate gaps in the actual divided-dose schedule, meals, adherence and equivalence conversion.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Link the original intake and adherence records to product identity to extract actual exposure." }, { "item_id": "N05", "question_type": "Treatment and observation duration", "question": "Have 3 months of treatment and 2 months of observation after discontinuation been separated?", "needed": "Results at the main time point of 3 months; treatment duration; original endpoint-specific results during the additional 2 months of observation after discontinuation", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid turning end-of-treatment results into a sustained effect over 5 months or an annual slope.", "application_exception": "Do not establish a sustained effect solely from the existence of additional observation.", "criterion": "Record the main time point/treatment and additional observation after discontinuation separately, and retain the scope for which direct results on maintenance are unavailable.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Extract actual renal-function results at each visit and post-discontinuation time point separately to retain the time boundaries." }, { "item_id": "N06", "question_type": "Actual population", "question": "Have the actual participants' diabetes, microalbuminuria and CKD stage been verified?", "needed": "Eligibility criteria for age 35–65 years, type 2 diabetes and persistent microalbuminuria; baseline renal function; CKD stage", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid extending early diabetic nephropathy to CKD of all causes/stages or to dialysis/transplantation.", "application_exception": "Do not replace the currently unspecified CKD stage with an arbitrary stage 1/2/3.", "criterion": "Retain the verified age/disease/albuminuria together with the unverified stage, and indicate population differences.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare original eligibility criteria, baseline distributions and stage data, and review direct comparisons by stage/cause separately." }, { "item_id": "N07", "question_type": "Nutritional status", "question": "Can correction of deficiency be distinguished from additional supplementation in nondeficient participants?", "needed": "Baseline plasma/dietary thiamine status; definition of deficiency; eligibility/analysis exclusions; renal-function results by status", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid harmonizing low plasma levels and indicators of dietary adequacy into a single deficient/nondeficient population.", "application_exception": "Do not confuse the analysis exclusion of 1 participant with high thiamine levels with uniform deficiency status across the whole population.", "criterion": "Distinguish verified status indicators from unverified uniform deficiency and separately attributable effects.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Link nutritional-status definitions and analyses by status to actual renal-function denominators." }, { "item_id": "N08", "question_type": "Comparator and background treatment", "question": "Has the actual balance of placebo and usual treatment been verified?", "needed": "Placebo identity; diabetes/blood-pressure treatment by arm; insulin; changes/rescue treatment; analytical adjustment", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid attributing differences in background treatment to thiamine's contribution.", "application_exception": "Compare the actual effect of interest and analysis without requiring every change in both arms to be identical.", "criterion": "Distinguish placebo/usual care from actual imbalances and unverified changes/adjustments.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare baseline/follow-up differences in concomitant treatment and their impact on analysis against the original materials." }, { "item_id": "N09", "question_type": "Allocation and concealment", "question": "At what level were randomization and concealment procedures reported?", "needed": "Actual procedures for the random-number table, central allocation and opaque envelopes; baseline balance; implementation records", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid claiming that allocation/concealment has been verified solely from the randomized-trial label.", "application_exception": "Distinguish reported procedures from an independent audit of implementation, and do not call the pilot trial a formal confirmatory trial.", "criterion": "Link the level of allocation/concealment recorded in the original source to unverified implementation and baseline limitations.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare allocation, concealment and baseline-characteristic data for the outcome of interest." }, { "item_id": "N10", "question_type": "Blinding and adherence", "question": "Have reported blinding and actual adherence/blinding success been distinguished?", "needed": "Blinding of participants, care providers and assessors; actual adherence rate; blinding success; deviations by arm", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid turning the double-blind label into actual balance of exposure or absence of bias.", "application_exception": "Do not remove post-allocation deviations or changes in measurement/treatment on the grounds that the formula-derived value is objective.", "criterion": "Record whose blinding was reported separately from gaps concerning success/adherence.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Link data on actual blinding, adherence and changes by arm to the original analysis." }, { "item_id": "N11", "question_type": "Renal-function measure", "question": "Have the formula, units and measurement boundaries of the value labeled GFR been verified?", "needed": "Original table notes on Cockcroft–Gault and creatinine/Jaffé; units; body-surface-area adjustment; measurement/assessment procedures", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid turning a formula-derived value into measured GFR, body-surface-area-adjusted eGFR or an annual slope.", "application_exception": "What was read in the current work was the retained extraction and the location of the notes, not a new audit of measurement in the original PDF.", "criterion": "Distinguish the formula, units and labeling from unverified measurement procedures/errors.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Check the table notes and original measurement/calculation procedures to extract results by the same measure and units." }, { "item_id": "N12", "question_type": "Endpoint hierarchy", "question": "Have the page's target and the original trial's primary endpoint been distinguished?", "needed": "The original trial's urinary-albumin primary endpoint; role of the GFR result; endpoint hierarchy in the registry/plan", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid automatically transferring a reduction in urinary albumin to improved renal function or inhibition of long-term progression.", "application_exception": "GFR being this page's target does not mean it was preregistered as the trial's primary endpoint.", "criterion": "Keep the page's renal-function target separate from the trial's primary urinary-albumin endpoint, and indicate the gap in comparison with the original plan.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare the registry and plan with the reported endpoint hierarchy, keeping urinary-albumin and renal-function results separate." }, { "item_id": "N13", "question_type": "Means and dispersion in the original table", "question": "Have the baseline and 3-month end means±SD been retained unchanged?", "needed": "S01 Table1: baseline/end means and SD by arm, units, time points and exact analyzed denominators", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid turning arm-specific baseline/end values and SD into change SD or causal-effect intervals.", "application_exception": "Do not fill in analyzed denominators from the 20/20 allocation or newly calculate the difference between the two time points.", "criterion": "Assign the original retained arm-specific means/SD to the correct time points/units, leaving gaps in analyzed denominators.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Extract the original table together with the analyzed denominator at each time point and the definition of dispersion." }, { "item_id": "N14", "question_type": "Descriptive difference and causal effect", "question": "Have the historical end-mean difference and the adjusted effect been distinguished?", "needed": "Originally reported between-group estimate; baseline-adjusted model; effect of interest; analysis population; interval", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid interpreting a simple difference in end means with baseline differences as thiamine's causal effect or harm.", "application_exception": "−7 is existing descriptive arithmetic in the manuscript, not a value calculated, estimated or prescribed in the current work.", "criterion": "Record the historical unadjusted end-mean difference separately from the unverified adjusted causal effect/interval.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare effect magnitude only when the original adjusted model, between-group estimate and analyzed denominators have been obtained." }, { "item_id": "N15", "question_type": "Randomized and analyzed denominators", "question": "Have the 20/20 allocation and actual GFR analyzed/completer denominators been distinguished?", "needed": "Numbers randomized, completing and analyzed for GFR by arm; the arm and scope of applicability of the 1-person exclusion", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid automatically using the 40 randomized participants as 40 analyzed participants or as 20/20 outcome denominators.", "application_exception": "From the existing record of 1 participant excluded from analysis, do not infer that an arm had 19 participants.", "criterion": "Distinguish allocation from analysis/completion, and preserve unverified denominators as null.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare the original flow diagram and analysis exclusions with the arm-specific denominators in the GFR table." }, { "item_id": "N16", "question_type": "Missing data and analysis populations", "question": "Have GFR missing data, analysis populations and change variance been verified?", "needed": "ITT/PP; handling of attrition/missing data; outcome-specific application of exclusions; paired-change SD/correlation", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid reconstructing missing-data handling or change CI from known marginal SD and randomized numbers.", "application_exception": "Do not label the analysis population ITT without the original source.", "criterion": "Retain the reported exclusion and unverified analysis/missing data and paired variance, without creating new estimates.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Link the original analysis population, missing-data/sensitivity handling and change variance to the outcome of interest." }, { "item_id": "N17", "question_type": "Precision and importance", "question": "Have the exact P, CI and clinical importance been verified?", "needed": "Original GFR between-group estimate/exact P and CI; justified important difference; denominators/model", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid concluding an effect of 0, exclusion of clinical benefit or equivalence from the word nonsignificant alone.", "application_exception": "Do not propose arbitrary numbers for sample size, duration or the minimum important difference.", "criterion": "Link the original intervals/importance criteria, or indicate why interpretation is not possible.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Obtain the original estimate, CI, exact P and endpoint-specific basis for importance to review the scope of interpretation." }, { "item_id": "N18", "question_type": "Interpretation of nonsignificance", "question": "Has a nonsignificant result been kept from being recast as an effect of 0 or equivalence?", "needed": "Original report of nonsignificant renal-function results; unverified estimates/CI; separate evidence for equivalence/exclusion of benefit", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid strengthening verified nonsignificant results into definitive favorable or unfavorable conclusions.", "application_exception": "Retain the record of nonsignificance, but do not use it to assign a new efficacy/safety grade.", "criterion": "Preserve the reported direction together with uncertainty, distinguishing them from a true effect of 0, equivalence or exclusion of benefit.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Review the original nonsignificant results together with intervals/denominators, avoiding an inaccurate interpretation as an effect of 0." }, { "item_id": "N19", "question_type": "Trial families and overlap", "question": "Have reports, mirrors and companion reports been kept from being summed as independent trials?", "needed": "TF01–TF08 families; original articles/mirrors; correspondence/companion reports; links for overlapping denominators/results", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid counting publisher/PubMed/author mirrors and companion analyses as independent replications/participants.", "application_exception": "Do not turn unverified participant overlap in companion reports into confirmation of either the same cohort or a different trial.", "criterion": "Distinguish verified families from provisional links, and preserve only their contributions to the direct locked result.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare family/registry/report/result/participant relationships to separate independent comparisons from potential overlaps." }, { "item_id": "N20", "question_type": "Critical letter and reply", "question": "Have the substantive content of the critical letter and the unread reply been distinguished?", "needed": "S03 critique/endpoint interpretation; S04 full reply; distinction between correspondence and corrections/retractions", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid claiming that the authors' substantive reply was read or turning correspondence into a new trial/correction.", "application_exception": "Do not automatically transfer the issue concerning urinary-albumin medians to an error in the GFR result.", "criterion": "Keep the scope of the verified critique separate from that of the unread reply.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare the full reply with the points in the original critique by endpoint, checking actual correction events separately." }, { "item_id": "N21", "question_type": "Companion reports and cohorts", "question": "Have the same participants and additional results in S05–S08 been verified?", "needed": "Registration, recruitment, populations and denominators; participant/result links between reports", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid adding companion analyses as new participants or direct replications.", "application_exception": "Do not establish that all of the same 40 participants were included solely from a shared registry lead.", "criterion": "Separate verified links from unverified participant-level overlap.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare full companion reports, recruitment/registration and denominators to verify cohort links." }, { "item_id": "N22", "question_type": "Registration and plans", "question": "Have a printed registration number and actual reading of the registry/plan been distinguished?", "needed": "CTRI2008/091/000112 actual registry record, dates, original protocol/SAP and outcome hierarchy", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid turning a printed number into comparison with the entire registry record or verification of the prespecified hierarchy.", "application_exception": "Do not use an access barrier as evidence of nonregistration.", "criterion": "Record the reported number, actual failure/nonreading and gaps in the prespecified hierarchy.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "In an authorized update, link the actual registry/plan and change history to the outcome hierarchy." }, { "item_id": "N23", "question_type": "Funding and independence", "question": "Have the levels of verification of public funding and conflict-of-interest declarations been distinguished?", "needed": "Reported funding; product provision/involvement; author relationships; scope of independent verification", "role": "Supplementary; required for claims of independence", "role_reason": "Required to avoid turning reported declarations into an independent audit of implementation or replication.", "application_exception": "Do not automatically exclude results or establish absence of bias solely from funding.", "criterion": "Retain reported declarations together with gaps in product involvement/independent verification.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare original funding, product provision and relationships, and review independent replication separately." }, { "item_id": "N24", "question_type": "Adjacent CKD3 results", "question": "What do the different stage, duration and eGFR change in S02 answer?", "needed": "S02 actual population, exposure/salt, definition of change over 24 weeks, analyzed denominators and original estimate/CI", "role": "Supplementary (adjacent comparison)", "role_reason": "Required to avoid transferring results with a different measure and duration into direct replication of the 3-month CG result.", "application_exception": "Do not fill in analyzed denominators from the randomization of 35 participants, 18/17.", "criterion": "Indicate the scope of the adjacent abstract and the unverified exposure/denominators and precision.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Verify actual exposure, change, denominators/intervals in the adjacent full text and review them as a separate question." }, { "item_id": "N25", "question_type": "Bibliography and adjacent families", "question": "Have S02 and S22 been kept from being counted as different trials?", "needed": "Online/print dates, DOI/institutional bibliography and links to the same TF02 report", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid adding an institutional bibliographic entry as an independent replication.", "application_exception": "Do not arbitrarily harmonize the 2025 online and 2026 print publication years into a single year.", "criterion": "Distinguish the bibliography of the same TF02 report and its different measure/duration relative to the locked question.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Retain links to the same DOI/report, and verify any new independent comparison separately." }, { "item_id": "N26", "question_type": "Provenance of the review estimate", "question": "Has the relationship between the review's 0.31 estimate and the original end means been verified?", "needed": "S12 estimand, denominators, additional-data/change definitions and links to original results", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid removing the possibility of a different analysis and automatically declaring an error or the same effect.", "application_exception": "Do not declare a review error or conflicting information solely from the current difference.", "criterion": "Retain the unverified link between the review's MD/CI and the original end means.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare the review's extraction table, estimand and additional data with the original results." }, { "item_id": "N27", "question_type": "Other derivatives", "question": "Has benfotiamine been transferred into a direct effect of ordinary thiamine?", "needed": "Distinctions between molecule/exposure, endpoints and trial families", "role": "Supplementary (boundary for other derivatives)", "role_reason": "Required to avoid attributing results and safety for other derivatives to ordinary thiamine.", "application_exception": "Retain the historical access limitations for S09.", "criterion": "Exclude the different derivative TF03 from the locked direct comparison.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Check the relevant original materials when separately reviewing a question about the derivative." }, { "item_id": "N28", "question_type": "Combination and dialysis data", "question": "Has the individual contribution been verified from combination products or multinutrient registry records?", "needed": "Combination ingredients; dialysis population; cognition/other endpoints; distinction between registry records and results", "role": "Supplementary (combination/dialysis boundary)", "role_reason": "Required to avoid turning combination results into the renal-function contribution of single-ingredient ordinary thiamine.", "application_exception": "Do not label a registry index record as completed results.", "criterion": "Separate S10 combination cognition data and the S18 multinutrient registry record from the locked direct comparison.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "For combination/dialysis questions, separately review the results and whether the individual contribution can be identified." }, { "item_id": "N29", "question_type": "Observational, acute and animal data", "question": "Have status associations, acute AKI and animal data been transferred into chronic oral effects?", "needed": "Distinctions between population/design, exposure, endpoints and data roles", "role": "Supplementary (data boundary)", "role_reason": "Required to avoid calling observational/acute/animal data a causal effect of chronic oral treatment in humans.", "application_exception": "Do not expand the scope of index/abstract reading into full-text review.", "criterion": "Retain the design and population differences in S19–S21.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "For each separate question, verify eligible direct materials and the scope actually read." }, { "item_id": "N30", "question_type": "Renal pharmacokinetics", "question": "Do single-dose 100 mg data in ESRD answer chronic 300 mg safety?", "needed": "S11 actual molecule, single dose/24 hours and ESRD; distinction between concentration/excretion and chronic harms", "role": "Supplementary; required for safety claims concerning repeated exposure", "role_reason": "Required to avoid turning pharmacokinetic exposure into chronic efficacy or prescribing by kidney-disease stage.", "application_exception": "Do not harmonize single-dose nitrate/benfotiamine with the trial's 300 mg regimen whose salt was not reported.", "criterion": "Separate the reported single-dose conditions from gaps concerning chronic harms/dose.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Separately verify pharmacokinetic/harm data for the same molecule, stage and repeated exposure." }, { "item_id": "N31", "question_type": "Separate authorized product", "question": "Has the identity of the S13 SmPC product and the trial product been established as the same?", "needed": "Authorized product identity, version, ingredients/warnings and whether it is the same as the trial product", "role": "Supplementary (product/safety context)", "role_reason": "Required to avoid substituting a separate regulated product for the unreported trial product.", "application_exception": "Do not turn an authorized product's doses/warnings into an individual CKD prescription.", "criterion": "Separate historical verification of the separate product from the unverified trial product.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Verify the relationship between the actual trial product and the authorized product, and the version/warnings." }, { "item_id": "N32", "question_type": "Official nutrition information and interactions", "question": "Does the absence of an established UL mean unlimited safety?", "needed": "Insufficient data in the official explanation; medication/exposure context; version; harms in the actual population", "role": "Supplementary; required for safety claims", "role_reason": "Required to avoid turning the absence of an established UL into high-dose CKD safety or unrestricted intake.", "application_exception": "Do not use general explanations as direct CKD trials or prescribing guidance.", "criterion": "Retain insufficient data and medication wording together with gaps in quantitative harms.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Compare official explanations separately with harms for the actual exposure/population concerned." }, { "item_id": "N33", "question_type": "Harms and event denominators", "question": "Have denominators for adverse reactions, serious events and discontinuations been verified?", "needed": "Arm-specific AE/SAE for the same exposure; collection/duration; exposure denominators; reasons for discontinuation", "role": "Supplementary; required for safety claims", "role_reason": "Required to avoid turning unverified quantitative harms into 0 events/0 risk.", "application_exception": "Do not transfer reactions to injectable products into oral incidence rates.", "criterion": "Retain unverified events/denominators and duration for the original harms data.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "Verify arm-specific harm collection, denominators/duration and discontinuations for the same oral regimen." }, { "item_id": "N34", "question_type": "Long-term and stage-specific safety", "question": "Have long-term accumulation and doses for special populations/by stage been verified?", "needed": "Actual data on repeated/long-term exposure, accumulation, doses by kidney-disease stage and vulnerable populations/concomitant use", "role": "Supplementary; required for those extension claims", "role_reason": "Required to avoid extending a short-term pilot trial into long-term/stage-specific prescribing.", "application_exception": "Do not require all extension studies as prerequisites for the narrow question about the mean at 3 months.", "criterion": "Indicate the scope for which direct long-term/special-population data are unavailable.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "For extension questions, review harms and direct dose comparisons for the same molecule, stage and repeated exposure." }, { "item_id": "N35", "question_type": "Long-term progression and events", "question": "Does the 3-month CG readout answer questions about annual slope or kidney-failure events?", "needed": "Direct endpoints of annual slope, dialysis/kidney failure/death in the same population/exposure", "role": "Supplementary; required for claims about long-term events", "role_reason": "Required to avoid turning a surrogate renal-function readout and urinary albumin into patient-centered inhibition of progression.", "application_exception": "Distinguish the status of the current narrow numerical question from that of the long-term-event question.", "criterion": "Do not claim annual slope and long-term events as direct locked results.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "For a long-term-progression question, review direct endpoints and adequate follow-up/denominators separately." }, { "item_id": "N36", "question_type": "Unacquired registry lead", "question": "Has the actual body of NCT06322212 been read?", "needed": "Actual structured registry body; eligibility/exposure; results/status; original change history", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid calling a JavaScript shell and CKD background descriptions actual participants/results.", "application_exception": "Do not automatically promote a registry lead to an eligible direct comparison or completed results.", "criterion": "Distinguish the unacquired body and failed access from background/eligibility criteria.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "In an authorized update, verify the actual registry body and results/changes to reconsider the boundaries." }, { "item_id": "N37", "question_type": "Search and correction scope", "question": "Have search attempts been distinguished from completed native-database/correction reviews?", "needed": "Cutoff date; search routes/results; actual scope of negative/unpublished results, registry records and corrections/retractions", "role": "Required (selected renal-function question)", "role_reason": "Required to avoid turning search errors, homepages and existing routes into exhaustive searches or current correction reviews.", "application_exception": "No new search in the current work does not mean 0 studies or no recent corrections.", "criterion": "Distinguish the historical 41 general-web searches from incomplete native lookups and the current local conversion.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "In a separately authorized update, record actual search/registry/correction results and the scope of failures." }, { "item_id": "N38", "question_type": "Original verdict and document quality", "question": "Are the existing D30 and document A being read as new clinical verification?", "needed": "Original grade/score; document assessment; verification actor; actual scope of conversion", "role": "Required (selected renal-function question)", "role_reason": "Required to separate document self-checking from clinical/safety certification.", "application_exception": "Do not use the current table's statuses/counts as a new efficacy score.", "criterion": "Preserve the original D30/Caution and document/self-checking records as historical values.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "If a new evidence event is authorized, link a separate version/decision to the clinical evidence." }, { "item_id": "N39", "question_type": "Reading, identity and updates", "question": "Are summary links and past publication metadata being read as verification of current original sources/publication?", "needed": "ID/URL; dates/revisions; historical/current reading by material; exact pointer/literal/SHA; update links", "role": "Required (selected renal-function question)", "role_reason": "Required to distinguish reading retained stored summaries from external clinical originals/public publication in the current work.", "application_exception": "Do not use a local stored-summary SHA as the hash of an external PDF's original bytes.", "criterion": "Link to the exact stored summary, and indicate current nonreading of external materials and local nonpublication.", "basis": "Chamgap's own adaptation of the retained M03/M04/M08/M15/M19 principles on questions, families, measurement/missing data, precision and interpretation of harms. This is not formal implementation or certification of those methods.", "condition_origin": "Development criteria individually written after actually reading the already known case 3121. This is not blinding, preregistration or independent clinical certification.", "proposed_research": "When new materials arrive, preserve everything before changes and reconsider the relevant rows, materials, criteria version and change decision." } ] }