{ "schema_version": "chamgap-public-criteria-1.0", "title": "Ordinary thiamine (vitamin B1) × HbA1c reduction in type 2 diabetes with CKD stage 3", "criteria_version": "1.0", "criteria_date": "2026-10-05", "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 conditions and reasons for changes; distinguish intervention variants.", "review_level": "Stored method principles, application records and copy hashes were checked. No new retrieval of external methods documents or execution of an entire official assessment tool was performed." }, { "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; do not omit studies solely because outcomes are unreported.", "review_level": "Stored method principles, application records and copy hashes were checked. No new retrieval of external methods documents or execution of an entire official assessment tool was performed." }, { "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": "Fix the outcome and effect of interest, then review randomization, deviations, missing data, measurement and selective reporting.", "review_level": "Stored method principles, application records and copy hashes were checked. No new retrieval of external methods documents or execution of an entire official assessment tool was performed." }, { "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 effects, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Stored method principles, application records and copy hashes were checked. No new retrieval of external methods documents or execution of an entire official assessment tool was performed." }, { "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": "Harm questions may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence.", "review_level": "Stored method principles, application records and copy hashes were checked. No new retrieval of external methods documents or execution of an entire official assessment tool was performed. Sections 19.1.2 and 19.2.1–19.2.4 of the stored harms chapter were additionally read." } ], "status_dictionary": { "Verified": "The specified record or boundary is verified in the stored material; this differs from confirmed efficacy or a new grade", "Partly verified": "Some parts of the condition are known while specific gaps remain", "Unverified": "The actual data or methods needed for the condition could not be verified within the currently stored material", "Unread": "External material was not read in this work; this differs from no research or an effect of 0", "Not applicable": "An extension condition outside this independent question; not a substitute for unread-material status" }, "condition_origin": "Chamgap’s own application conditions", "requirements": [ { "item_id": "N01", "question_type": "Question boundaries", "question": "What single question is defined by this table's population, thiamine, route, comparator, duration and HbA1c endpoint?", "needed": "Records identifying the current question and the direct trial's population, route, formulation, duration and comparator.", "role": "Required", "role_reason": "Changing the population or clinical endpoint would produce a different effect table.", "application_exception": "Primary (1st) renal outcomes, benfotiamine, injections and other diabetes populations are not reused as direct results for this claim.", "criterion": "Fix the question as HbA1c change with ordinary single-ingredient oral thiamine, 300 mg/day for 24 weeks versus placebo, in adults with T2D and CKD stage 3; distinguish other renal conditions, molecules and endpoints.", "basis": "M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed; M03 §3.2.2–3.2.3; direction labels and test adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations are question-specific internal designs", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "When collecting new material, apply these eligibility criteria and separately record excluded molecules, renal conditions and endpoints." }, { "item_id": "N02", "question_type": "Population selection", "question": "Can the direct trial's full CKD stage 3 and T2D inclusion and exclusion criteria be verified?", "needed": "The direct trial's diagnostic, eGFR, age, inclusion and exclusion criteria, and recruitment flow.", "role": "Required", "role_reason": "Microalbuminuria and CKD3 cannot be assumed to define the same population.", "application_exception": "S01's microalbuminuria criteria are not used to fill gaps in S02's CKD3 selection criteria.", "criterion": "Beyond identifying CKD3 and adult T2D, verify diagnostic criteria, renal-function ranges, age, exclusions and recruitment setting, or specify the unverified parts.", "basis": "M03 §3.2.1; detailed population conditions are internally designed; M08 §8.1–8.2.3; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "In comparative studies defining the same population, record criteria and recruitment flow in advance and separate other renal conditions." }, { "item_id": "N03", "question_type": "Baseline B1 status", "question": "Were baseline thiamine status and the method for identifying deficiency verified in the eligible population?", "needed": "Baseline thiamine assay, concentrations, deficiency criteria and arm-level distributions.", "role": "Supplementary; required for extensions to deficient populations", "role_reason": "Results in a general study population must not be conflated with treatment effects in deficiency.", "application_exception": "Deficiency-specific effects are not mandatory for the narrow HbA1c question; unknown status is not filled in as deficient or non-deficient.", "criterion": "Verify baseline B1 measurement, units, deficiency criteria and population distribution; distinguish deficiency screening from effect-modification analysis.", "basis": "M03 §3.2.1; detailed population conditions are internally designed; M03 §3.2.1–3.2.4; detailed dose, persistence and effect-modification conditions are internally designed", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "In studies measuring deficiency status in advance, separately analyse stratum-specific effects and interactions." }, { "item_id": "N04", "question_type": "Formulation identity", "question": "To what extent are ordinary thiamine's exact salt, release formulation, manufacturer and single-ingredient status verified?", "needed": "Trial-product ingredients, salt, release formulation, manufacturer and batch specifications.", "role": "Required", "role_reason": "Trials of different molecules or formulations must not be combined as identical exposures.", "application_exception": "Benfotiamine, injections or other salts do not fill gaps in the unconfirmed product specifications.", "criterion": "Distinguish the identity of ordinary single-ingredient thiamine capsules from the exact salt, release formulation and manufacturing origin; do not fill unconfirmed details.", "basis": "M03 §3.2.2–3.2.3; direction labels and test adaptations are internally designed", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Preserve product specifications in single-ingredient comparisons with identified formulations; screen benfotiamine and combination products separately." }, { "item_id": "N05", "question_type": "Actual route", "question": "Was actual oral administration verified in the direct trial?", "needed": "Records of the trial intervention's actual administration route.", "role": "Required", "role_reason": "The planned route must be distinguished from the route actually used.", "application_exception": "Verification of an oral route does not verify effects of injections or oral bioavailability.", "criterion": "Compare the planned question route with the observed trial route and link the source location supporting actual oral administration.", "basis": "M03 §3.2.2–3.2.3; direction labels and test adaptations are internally designed", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Manage studies using other routes in separate eligibility groups; do not combine them with oral results." }, { "item_id": "N06", "question_type": "Administered dose", "question": "Are the nominal doses of 300 mg/day and 150 mg/capsule, and actual exposure, verified?", "needed": "Trial dosing instructions, frequency, medication-taking records and actual intake.", "role": "Required", "role_reason": "Differences between nominal dose and actual exposure may affect the analysis.", "application_exception": "Do not convert 300 to another unit or total dietary B1; do not turn the study dose into individual dosing instructions.", "criterion": "Link the nominal daily and per-capsule doses; verify dosing frequency, actual intake and adherence separately.", "basis": "M03 §3.2.2–3.2.3; direction labels and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Collect medication-taking records in same-dose comparisons; distinguish actual-exposure analysis from the effect of assignment." }, { "item_id": "N07", "question_type": "24-week time point", "question": "Are the treatment duration and measurement time point of the direct HbA1c result verified?", "needed": "The 24-week treatment and measurement schedule, with time-point labels for each result.", "role": "Required", "role_reason": "S20's on-treatment and post-treatment time points must not be combined with the current 24-week question.", "application_exception": "Verification of duration does not establish persistence of the effect afterward.", "criterion": "Link 24 weeks of treatment to the corresponding HbA1c change time point; separate subsequent persistence.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations are question-specific internal designs; M03 §3.2.1–3.2.4; detailed dose, persistence and effect-modification conditions are internally designed", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Prespecify measurement times for each outcome and report post-treatment follow-up as a separate outcome." }, { "item_id": "N08", "question_type": "Comparator composition", "question": "To what extent are the placebo comparator's identity, exact composition and masking conditions verified?", "needed": "Placebo ingredients, appearance, allocation codes and masking procedures.", "role": "Required", "role_reason": "The comparator's own exposure and measurement differences must not be misattributed to B1.", "application_exception": "The labels RCT or placebo alone do not establish successful double masking or allocation concealment.", "criterion": "Verify the placebo comparison and distinguish its composition, appearance, presence of active ingredients and details of masking implementation.", "basis": "M03 §3.2.2–3.2.3; direction labels and test adaptations are internally designed; M08 §8.1–8.2.3; internal application; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "In comparisons using a matched placebo, record composition, masking procedures and their success." }, { "item_id": "N09", "question_type": "Background treatment", "question": "Can diabetes treatments, rescue medication and treatment changes in both arms be verified?", "needed": "Arm-level diabetes medications, renal treatments, and changes or rescue-treatment records.", "role": "Required", "role_reason": "Differences in other treatments must not be attributed to the contribution of added thiamine.", "application_exception": "Do not require all medication changes to be identical; verify the actual effect of interest and how changes were handled.", "criterion": "Verify arm-level drugs, doses, changes, rescue treatment and analytical handling, or retain these as limitations on attributing the intervention's contribution.", "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.2–3.2.3; direction labels and test adaptations are internally designed", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Prespecify background care and rescue criteria, report changes by arm and link them to analysis of the assignment effect." }, { "item_id": "N10", "question_type": "Total exposure", "question": "Are total dietary B1 and concurrent-vitamin exposures verified by arm?", "needed": "Arm-level dietary B1, supplements and concurrent-vitamin intake records.", "role": "Supplementary; required to interpret exposure contributions", "role_reason": "Exposure outside the trial medication must not be assumed equal.", "application_exception": "An empty linked-source list does not mean no concurrent vitamins were used; do not arbitrarily reclassify this as a combination-product trial.", "criterion": "Distinguish the trial supplement dose from total diet, other supplements and concurrent vitamins.", "basis": "M03 §3.2.2–3.2.3; direction labels and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "In comparisons measuring concurrent exposures, record total intake and background vitamins to analyse the applicability of the main effect." }, { "item_id": "N11", "question_type": "Allocation implementation", "question": "Are randomization sequence, concealment and baseline balance verified?", "needed": "Trial methods describing sequence generation, concealment, separation of responsibilities and the baseline table.", "role": "Required", "role_reason": "An RCT label does not replace review of bias in its implementation.", "application_exception": "Do not judge small samples or unread full texts as evidence of actual randomization failure.", "criterion": "Distinguish the randomized placebo-controlled design from actual sequence generation, concealment responsibilities and baseline balance.", "basis": "M08 §8.1–8.2.3; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Report implementation methods and arm-level baseline data in randomized comparisons, with planning before analysis." }, { "item_id": "N12", "question_type": "Baseline glycaemia", "question": "Can baseline HbA1c, renal function and balance of relevant prognostic factors be verified in both arms?", "needed": "S02 arm-level baseline HbA1c, eGFR, medications, prognostic factors and adjustment plan.", "role": "Required", "role_reason": "Baseline differences and values from another trial family must not be conflated with the direct trial's effect.", "application_exception": "Do not assume a simple between-group median-change contrast necessarily uses a baseline-adjusted model.", "criterion": "Verify the direct trial's arm-level baseline outcomes, renal status and analytical adjustment variables.", "basis": "M03 §3.2.1; detailed population conditions are internally designed; M08 §8.1–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Report outcome tables including baseline values and prespecified adjustment models to assess the implications of imbalance." }, { "item_id": "N13", "question_type": "Adherence and treatment deviations", "question": "Are medication adherence, intervention deviations, rescue treatment and their handling verified?", "needed": "Medication-taking records, arm changes, intervention discontinuation, rescue treatment and analytical handling.", "role": "Required", "role_reason": "The contribution of the chosen intervention must be distinguished from actual deviations.", "application_exception": "Treatment discontinuation and missing follow-up are separate; do not use the same denominator without support.", "criterion": "Verify actual medication-taking, arm changes, rescue drugs and how assignment effects and adherence effects were handled.", "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "In comparisons collecting post-allocation deviation data, plan assignment-effect and adherence-effect analyses separately." }, { "item_id": "N14", "question_type": "HbA1c measurement", "question": "Are the HbA1c assay, units, quality control and arm-level measurement conditions verified?", "needed": "HbA1c assay, units, blood-sampling schedule, quality control and assay-interference information.", "role": "Required", "role_reason": "Differences in measurement conditions must not be mistaken for differences in effects.", "application_exception": "An objective blood test alone does not establish absence of measurement bias or interference.", "criterion": "Specify the HbA1c assay, units, collection schedule, assessment conditions and scope of interference verification.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations are question-specific internal designs; M08 Table 8.2.a, M03 §3.2.4; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Use matching assays and measurement schedules, assess interference and report criteria before analysis." }, { "item_id": "N15", "question_type": "Endpoint hierarchy", "question": "Is the reported hierarchy of the primary (1st) renal outcome and secondary (2nd) HbA1c outcome verified?", "needed": "The trial's description of primary and secondary endpoints and their results.", "role": "Required", "role_reason": "A favourable secondary (2nd) result must not be recast as a successful primary (1st) result.", "application_exception": "A nonsignificant primary renal outcome does not prove an HbA1c effect of 0 and is not used for new clinical regrading.", "criterion": "Distinguish the paper's primary endpoint from this page's endpoint; preserve the original primary (1st) nonsignificant and secondary (2nd) positive findings.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations are question-specific internal designs; M08 Table 8.2.a, M04 §4.6.3; internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Report analyses and multiplicity plans with primary and secondary (2nd) endpoints distinguished in advance." }, { "item_id": "N16", "question_type": "Prespecified plan", "question": "Can HbA1c timing, analysis and multiplicity be compared against registration, protocol and SAP?", "needed": "S02's original registration, time history, protocol, SAP and complete results.", "role": "Required", "role_reason": "Gaps in the material needed to assess selection of favourable findings must be made explicit.", "application_exception": "Do not turn unverified registration into confirmed nonregistration, selective reporting or absence of research.", "criterion": "Distinguish the registrations or plans actually compared from material not acquired; verify HbA1c prespecification and analysis changes.", "basis": "M08 Table 8.2.a, M04 §4.6.3; internal application; M04 §4.5, §4.6.3; the limits of this material conversion follow the user's scope and internal design", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Prespecify HbA1c analyses, time points and multiplicity handling; compare them with results and reasons for changes." }, { "item_id": "N17", "question_type": "Analysis population", "question": "Are the allocated, completing and actually analysed populations and analysis-set definition verified for 24-week HbA1c?", "needed": "Outcome-specific analysis n for 24-week HbA1c, allocation/completion flow and analysis-set definitions.", "role": "Required", "role_reason": "Allocated participants cannot fill gaps in the outcome denominator or precision.", "application_exception": "Do not automatically use 18/17 as the HbA1c analysis n, completion n or safety n.", "criterion": "Distinguish allocation of 18/17 from actual HbA1c analysis n; verify ITT/PP and the outcome contributors.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Report outcome-specific flow and analysis denominators; specify assignment-effect and available-outcome analyses." }, { "item_id": "N18", "question_type": "Missing-data handling", "question": "Can the extent and handling of missing HbA1c data, losses and discontinuations be verified?", "needed": "HbA1c measurement losses, discontinuation and dropout reasons, missing-data handling and sensitivity analyses.", "role": "Required", "role_reason": "The limitations that losses and analysis impose on interpretation must be identified.", "application_exception": "Do not newly calculate missing counts or dropout rates from allocation and completion counts belonging to another trial family.", "criterion": "Distinguish outcome-specific loss reasons and timing, intervention discontinuation and missing follow-up; verify handling and sensitivity analyses.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Report outcome-specific missingness reasons and prespecify suitable missing-data assumptions and sensitivity analyses." }, { "item_id": "N19", "question_type": "Effect measure", "question": "Which between-group median-change comparison and analysis does the estimate −1.35 represent?", "needed": "Arm-level HbA1c change distributions, the between-group estimand definition and analysis model.", "role": "Required", "role_reason": "Medians must not be conflated with means, or between-group comparisons with within-group changes.", "application_exception": "S20's arithmetic on mean changes does not establish the model for this between-group median-change contrast.", "criterion": "Distinguish the reported between-group median-change contrast from within-group changes, final values and adjusted mean differences; verify the analysis model.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations are question-specific internal designs; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Prespecify the HbA1c effect of interest and method for estimating the median-change contrast; report the model and denominator." }, { "item_id": "N20", "question_type": "Reported-value units", "question": "To what extent are the HbA1c contrast of −1.35 and its units verified?", "needed": "An original results table, full paper or correction explicitly identifying the units of −1.35.", "role": "Required", "role_reason": "Without units, clinical magnitude and direct comparison with other trials cannot be established.", "application_exception": "Do not retroactively assign customary HbA1c units or S20's % units to this value.", "criterion": "Both the reported value and units must be verified to interpret magnitude; do not assume unreported units such as percentage points (%p).", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations are question-specific internal designs; M15 §15.3.1–15.3.3; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "State HbA1c units and changes in outcome reports; provide the between-group estimate and dispersion together." }, { "item_id": "N21", "question_type": "Significance reporting", "question": "To what extent are the P value and model for this HbA1c test verified?", "needed": "S02's test type, exact P value and analysis results table.", "role": "Required", "role_reason": "A record of statistical significance alone must not establish sufficiency or clinical importance.", "application_exception": "Do not reverse-convert a P threshold into SE/SD/CI or a user's probability of success.", "criterion": "Distinguish verification of the reported P threshold, exact P value and testing model; do not convert these into effect dispersion, CI or importance.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations are question-specific internal designs; M15 §15.3.1–15.3.3; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Report estimates, intervals and testing models together; do not determine clinical importance from significance alone." }, { "item_id": "N22", "question_type": "Dispersion and intervals", "question": "Can the CI, dispersion and denominator of the direct HbA1c contrast be verified?", "needed": "S02's between-group HbA1c CI, dispersion, analysis n and model.", "role": "Required", "role_reason": "Significance or allocation n must not fill gaps in intervals and dispersion.", "application_exception": "Do not substitute renal-outcome CIs or another trial's means/SD for the current HbA1c contrast.", "criterion": "Link the CI, dispersion and actual analysis n for the same endpoint, time point and analysis; do not generalize material not acquired to nonreporting throughout the full paper.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M15 §15.3.1–15.3.3; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Report estimates and confidence intervals for the same effect of interest; specify missing-data and adjustment assumptions." }, { "item_id": "N23", "question_type": "Important difference", "question": "Can an applicable clinically important HbA1c difference and its relationship to the interval be verified for this population?", "needed": "Evidence supporting an applicable important difference for CKD3/T2D HbA1c, and units/CI for the direct contrast.", "role": "Supplementary; required for claims of clinical importance", "role_reason": "A laboratory signal must be distinguished from improvement meaningful to patients.", "application_exception": "Do not substitute an unverified criterion with no clinical effect or failure to meet an MCID; do not require an event trial for the narrow laboratory-value question.", "criterion": "Units, an interval and a justified important difference are needed to interpret their relationship; retain the unverified criterion.", "basis": "M15 §15.3.1–15.3.3; internal application; M03 §3.2.4; internally designed extension boundaries", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Assess the interval against a previously justified important difference without inventing minimum sample sizes, durations or efficacy grades." }, { "item_id": "N24", "question_type": "Unfavourable context", "question": "How should S01's lack of glycaemic benefit be read alongside the direct CKD3 result?", "needed": "S01's glycaemic results, population, duration and analysis details, compared with S02.", "role": "Required", "role_reason": "Earlier no-difference reports must not be deleted while retaining only the positive direct finding.", "application_exception": "Do not extend the abstract's no-effect wording to proof of an effect of 0 for all B1, all T2D or CKD3.", "criterion": "Retain unfavourable context; distinguish whether findings address the same question using actual differences in population, duration and endpoints.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M03 §3.2.1; detailed population conditions are internally designed", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Directly compare only studies addressing the same question; analyse other renal populations as stratified context." }, { "item_id": "N25", "question_type": "Same trial family", "question": "Were S01 and S20's shared registration number distinguished from independent replication?", "needed": "S01/S20 registration numbers, cohort linkage and outcome-specific participant flow.", "role": "Required", "role_reason": "Report counts must not be converted into independent replications or unique participant counts.", "application_exception": "Retain different outcomes under the same registration number, distinguishing their time points and analyses.", "criterion": "Link report identities, study identifiers and same/different family relationships as recorded; do not sum unverified total participant counts.", "basis": "M04 §4.6.1–4.6.2 on distinguishing studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Maintain a family map linking reports to unique trials and identify overlapping participants and analyses separately." }, { "item_id": "N26", "question_type": "Historical time-point values", "question": "Which time points do S20's on-treatment and post-treatment HbA1c values and historical arithmetic represent?", "needed": "S20 Table2's time-specific values, analysis denominators and original arithmetic records.", "role": "Required", "role_reason": "Improvement after discontinuation must not be reclassified as an on-treatment effect.", "application_exception": "Do not reuse arithmetic on rounded means in the original source as the current trial's adjusted mean difference, median difference or a new calculation.", "criterion": "Separate baseline, 3-month treatment-end and 2-month off-treatment means and historical calculations; do not reuse them as the current 24-week median effect.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations are question-specific internal designs; M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M03 §3.2.1–3.2.4; detailed dose, persistence and effect-modification conditions are internally designed", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Prespecify on-treatment and post-treatment results as separate effects of interest; provide values and intervals for the same analysis." }, { "item_id": "N27", "question_type": "Direct replication", "question": "Are independent replication and study counts verified for the same CKD3/24-week question?", "needed": "Eligible-study identities, families, funding and results for the same question.", "role": "Supplementary; required for replication extensions", "role_reason": "Adjacent material or reports under the same registration must not be counted as independent replications.", "application_exception": "Do not discard a result merely because it belongs to a single direct family. Without an exhaustive search, do not claim that only 1 direct study exists worldwide.", "criterion": "Distinguish direct and adjacent trial families; limit unique-study and participant counts to what the stored material verifies.", "basis": "M04 §4.6.1–4.6.2 on distinguishing studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; Chamgap's own independence/attribution conditions. The referenced official sections do not certify every detail of these conditions", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Screen independent comparisons addressing the same question; compare condition differences and unfavourable findings by trial family." }, { "item_id": "N28", "question_type": "Funding and COI", "question": "Are S02's funding, product provision, author employment/patents and declared interests verified?", "needed": "The direct paper's funding, COI, product provision and author/patent information.", "role": "Supplementary; required for independence claims", "role_reason": "Unverified funding must not be described as independent research or manufacturer-only research.", "application_exception": "Unconfirmed funding or company product provision alone does not automatically exclude a result or establish the magnitude of bias.", "criterion": "Identify declarations, resources, product provision and unknowns by location; do not treat I1 as proof of actual mixed funding.", "basis": "Chamgap's own independence/attribution conditions. The referenced official sections do not certify every detail of these conditions", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "In independent comparisons disclosing funding and product provision, record each party's role and analytical involvement." }, { "item_id": "N29", "question_type": "Persistence and dose extensions", "question": "Can persistence beyond 24 weeks, an optimal dose or effects in particular subgroups be directly verified?", "needed": "Post-treatment CKD3 follow-up, direct dose comparisons and prespecified subgroup/interaction results.", "role": "Supplementary; required for extension claims", "role_reason": "The chosen main effect must not be extended to maintenance effects or an optimal dose.", "application_exception": "Do not make all extension studies mandatory for verifying the current narrow 24-week question.", "criterion": "Verify post-treatment/long-term, direct dose-comparison and prespecified stratum/interaction information separately; do not infer these from the main effect.", "basis": "M03 §3.2.1–3.2.4; detailed dose, persistence and effect-modification conditions are internally designed; M03 §3.2.1; detailed population conditions are internally designed", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Design post-treatment follow-up, dose comparisons and prespecified stratum analyses separately from the current question; report estimates for each." }, { "item_id": "N30", "question_type": "Extension to clinical events", "question": "Does HbA1c change also answer questions about preventing complications or death, or improving quality of life?", "needed": "Direct comparative evidence on clinical events and quality of life under the same population and exposure conditions.", "role": "Supplementary; required for clinical-event extensions", "role_reason": "A laboratory signal must not be converted into event prevention or replacement of existing medication.", "application_exception": "Unverified event trials are not a reason to delete the reported HbA1c value or assert no effect.", "criterion": "Separate the glycaemic laboratory surrogate from clinical-event questions; do not extend the claim without direct event outcomes.", "basis": "M03 §3.2.4; internally designed extension boundaries; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations are question-specific internal designs", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Evaluate clinical-event questions in studies with separately prespecified outcome definitions, durations and denominators." }, { "item_id": "N31", "question_type": "Adverse-event accounting", "question": "Can event definitions, collection and denominators underlying the statement that no serious adverse events were reported be verified?", "needed": "S02 adverse-event and serious-event definitions, arm-level counts, exposure denominators, collection and discontinuation tables.", "role": "Supplementary; required for safety claims", "role_reason": "Efficacy summaries and harm information have different verification levels.", "application_exception": "Do not delete the HbA1c value because of safety-data gaps or automatically use allocation of 18/17 as the safety-analysis denominator.", "criterion": "Distinguish a nonreporting statement from actual event counts, people, collection methods and duration; do not promote it to 0 events or a safety guarantee.", "basis": "M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed distinctions are internally designed; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality tool was applied", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "For the same exposure and population, report systematic harm collection, exposure time, event/person counts and discontinuation reasons." }, { "item_id": "N32", "question_type": "Interactions", "question": "Are interactions and assay effects of concurrent exposures, including diabetes medications, verified?", "needed": "Arm-level concomitant exposures and relevant interaction or assay-effect information.", "role": "Supplementary; required for concomitant-use safety extensions", "role_reason": "Effects of concurrent medication and underlying disease must not be attributed to a single exposure.", "application_exception": "Do not turn a search not performed into confirmed interaction or absence of risk.", "criterion": "Specify separate interaction searches, actual concomitant exposure and review scope; do not interpret an unperformed search as no risk.", "basis": "M19 §19.1.2–19.2.4; internal application; M19 §19.2.2–19.2.4 on design considerations; detailed confounding records are internally designed; M19 §19.1.2–19.2.4; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "In safety studies collecting concomitant exposures, distinguish underlying disease and assay effects in the assessment." }, { "item_id": "N33", "question_type": "Long-term and rare harm", "question": "Can long-term or rare harms beyond 24 weeks and safety in vulnerable groups be directly verified?", "needed": "Long-term and rare-event data, vulnerable-group exposure/collection data and suitable comparisons.", "role": "Supplementary; required for broader safety claims", "role_reason": "Limited observations must not be extended to overall safety.", "application_exception": "Do not require every rare-harm study as an additional prerequisite for reporting the HbA1c value.", "criterion": "Distinguish harm duration and extensions for the direct exposure/population; do not rule out rare risks because the sample is limited.", "basis": "M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; internal application", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Collect rare events and vulnerable-group events through long-term follow-up or suitable observational designs; report denominators and concomitant exposures." }, { "item_id": "N34", "question_type": "Current versus historical reading", "question": "Was reading the stored summary in this work distinguished from each paper's historical access level?", "needed": "Stored manuscript summary, bibliography, historical access levels, source locations and individual access-date records.", "role": "Required", "role_reason": "Links, summaries and historical access records must not be recast as current full-text reading.", "application_exception": "Do not copy S20's historical HTML access to S01/S02 full papers or current successful HTML access.", "criterion": "Distinguish the stored manuscript actually read here from historical abstract/HTML access by material and date; retain current external full-text unread status.", "basis": "M04 §4.5–4.6 on collecting/selecting material; access/reading separation and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; the limits of this material conversion follow the user's scope and internal design", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "Maintain collection records identifying attempts, acquisition and reading levels by material, linked to original locations and versions." }, { "item_id": "N35", "question_type": "Search and update scope", "question": "What are the stored evidence date, current review date and search/correction scope?", "needed": "Historical search records, correction/retraction/registration-check scope, and dates and identities of new material.", "role": "Required", "role_reason": "Absence of studies outside the search scope must not be claimed.", "application_exception": "Historical search and numeric records and the original reused162 material were not opened here; only their reference strings are retained.", "criterion": "Distinguish the 2026-09-15 evidence date from the 2026-10-05 conversion review; qualify non-exhaustive searches and update triggers by scope.", "basis": "M04 §4.5, §4.6.3; the limits of this material conversion follow the user's scope and internal design; M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "For separately authorized updates, record eligible searches and registration/correction tracking; preserve previous values and reasons for changes." }, { "item_id": "N36", "question_type": "Original assessment preservation", "question": "Were original C46, axes, blank values/empty lists and corrections distinguished from new condition-status judgments?", "needed": "The current manuscript's grade/score/axes, original observed-evidence/nutrition fields, corrections and existing calculation records.", "role": "Required", "role_reason": "The original grade and model statuses must not be merged into a single quality or efficacy score.", "application_exception": "A structural PASS and model review do not constitute official method execution, independent clinical certification or completed publication.", "criterion": "Link original values, historical assessments and calculations unchanged; do not automatically inherit them as condition statuses, new scores or probabilities.", "basis": "M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed; M04 §4.5, §4.6.3; the limits of this material conversion follow the user's scope and internal design", "condition_origin": "Individually designed for the known development case in the stored 3084 records; family definitions are model-review inputs, not a fixed row-count form", "proposed_research": "When a change is needed, separately preserve the entire original text, version, reason and date; distinguish clinical regrading from display conversion." } ], "language": "en", "translation_date": "2026-10-29" }