{ "schema_version": "chamgap-public-criteria-1.0", "title": "Ordinary thiamine (vitamin B1), single-ingredient oral use × Whether usual gait speed improves in older adults with objectively impaired physical function", "criteria_version": "v3118-ORAL-THIAMINE-USUAL-GAIT-1.0", "criteria_date": "2026-10-05", "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": "Historical reuse of the retained HTML copies/SHA for 1585 and the methodological principles from that time. This is not new reading of the full methodological sources, official implementation or clinical certification in this review." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish and link studies and reports, and do not omit a study solely because its outcomes are not reported.", "review_level": "Historical reuse of the retained HTML copies/SHA for 1585 and the methodological principles from that time. This is not new reading of the full methodological sources, official implementation or clinical certification in this review." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting.", "review_level": "Historical reuse of the retained HTML copies/SHA for 1585 and the methodological principles from that time. This is not new reading of the full methodological sources, official implementation or clinical certification in this review." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Historical reuse of the retained HTML copies/SHA for 1585 and the methodological principles from that time. This is not new reading of the full methodological sources, official implementation or clinical certification in this review." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Questions about harms may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence.", "review_level": "Historical reuse of the retained HTML copies/SHA for 1585 and the methodological principles from that time. This is not new reading of the full methodological sources, official implementation or clinical certification in this review." } ], "status_dictionary": { "Met": "The relevant identity, material attribution, retained scope or boundary has been verified. This is not confirmation of clinical benefit/safety or official certification.", "Partly verified": "Some populations, values or methods in the record are retained, but verification dimensions needed for the question remain unresolved.", "Unverified": "Required materials/values cannot be established within the retained scope read. This does not mean no studies, an effect of 0 or 0 events.", "Conflicting information": "Retain the record of notation/aggregation discrepancies in the relevant indirect original report. Do not create conflicts through new calculations or solely from numerical differences between different analyses.", "Not applicable": "An extension requirement that does not apply to the outcome conditions of the current narrow question; it does not replace unverified materials.", "Does not apply": "An extension requirement that does not apply to the outcome conditions of the current narrow question; it does not replace unverified materials.", "Not reported": "An information gap at the retained location actually read; not a declaration that the information is unreported throughout the external article.", "Inaccessible": "Requires an actual failed access attempt in the current review; lack of an attempt in this review must be distinguished from a historical failure.", "Review incomplete": "Individual review pending during table preparation, separate from unverified materials or unread source materials." }, "requirements": [ { "item_id": "N01", "question_type": "Claim identity", "question": "Is the distinct boundary of the gait-speed question clear?", "needed": "Precisely link the original /ko/effect to the boundaries of older adults with objective functional impairment, single-ingredient oral thiamine and usual gait speed. Required source materials: The original text and identity fields of the current distinct claim, and the complete previous version if changed.", "role": "Required", "role_reason": "This identity criterion is needed to avoid combining all evidence on the ingredient or related functional studies into a single efficacy claim.", "application_exception": "Do not automatically generate additional gait-speed claims from results for grip strength, fatigue, Barthel/FIM, falls or cardiac measures.", "criterion": "Precisely link the original /ko/effect to the boundaries of older adults with objective functional impairment, single-ingredient oral thiamine and usual gait speed.", "basis": "M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M03 §3.2.4; internally defined extension boundaries — this is an item-specific adaptation for claim identity, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Break the original question down into population, exposure, comparator, measure and time point, and reconsider its identity only when a new claim arises." }, { "item_id": "N02", "question_type": "Retained search scope", "question": "As of which date and within which search scope are direct results unverified?", "needed": "Distinguish the evidence cutoff, actual review date, whether a search was performed and whether absence was proven. Required source materials: Historical search strategies, periods, database-specific result sets, failure records and authorized updated-search records.", "role": "Required", "role_reason": "This criterion limits the timing and scope of verification conveyed by the term unverified.", "application_exception": "Do not claim that the latest retractions, corrections or unpublished studies have been checked merely by reusing an earlier search.", "criterion": "Distinguish the evidence cutoff, actual review date, whether a search was performed and whether absence was proven.", "basis": "M04 §4.5, §4.6.3; limitations on the current material conversion follow the user-defined scope and internal design; M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed — this is an item-specific adaptation for retained search scope, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "If an update is authorized, hold the eligibility criteria for the same question fixed, compare the search/selection flow and exclusion reasons, and retain the original record of 0." }, { "item_id": "N03", "question_type": "Reading level", "question": "Was reading the stored summary distinguished from reading the corresponding source material?", "needed": "Reading of the local summary must be consistent with current non-reading of external/historical separate materials and their historical access levels. Required source materials: Each material's original document, version, URL identity, directly read location/date and actually acquired bytes/SHA.", "role": "Required", "role_reason": "This is a required traceability criterion to prevent false reading badges and confusion about report types.", "application_exception": "Not attempting access is not an access failure, and the SHA of the stored source summary is not the SHA of an external PDF or registry document.", "criterion": "Reading of the local summary must be consistent with current non-reading of external/historical separate materials and their historical access levels.", "basis": "M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limitations on the current material conversion follow the user-defined scope and internal design — this is an item-specific adaptation for reading level, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "If access is separately authorized, record attempts, successes, acquisition and reading separately for each document, and compare them with the summary links used in this review." }, { "item_id": "N04", "question_type": "Population selection", "question": "Were the criteria for older age and objective functional impairment verified?", "needed": "Verify the definition of objective functional impairment in the question's population and its match to or differences from actual study participants. Required source materials: Eligibility criteria, baseline functional testing, participant flow and actual age/comorbidity tables.", "role": "Required", "role_reason": "This is needed to avoid applying material with an unverified population match as direct efficacy evidence.", "application_exception": "Do not automatically establish objective functional impairment from older age or a diagnosis of heart failure or CKD alone.", "criterion": "Verify the definition of objective functional impairment in the question's population and its match to or differences from actual study participants.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M08 §8.1–8.2.3; internal application — this is an item-specific adaptation for population selection, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "In a comparative study of older adults with a prespecified functional-impairment instrument and cutoff, compare measurements at selection with the participants actually included." }, { "item_id": "N05", "question_type": "Baseline nutritional status", "question": "Was selection for deficiency distinguished from selection for functional impairment?", "needed": "Attribute baseline deficiency, functional impairment and measurement markers to their respective populations and analyses. Required source materials: Thiamine-status testing methods, baseline diet/nutrition tables, deficiency criteria and prespecified subgroup plans.", "role": "Supplementary; required for claims of applicability by deficiency status", "role_reason": "This supplementary criterion separates the question boundaries for deficiency management and additional supplementation.", "application_exception": "Selection for deficiency using criteria for a different specimen does not by itself establish eligibility as a population with functional impairment.", "criterion": "Attribute baseline deficiency, functional impairment and measurement markers to their respective populations and analyses.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are internally designed — this is an item-specific adaptation for baseline nutritional status, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Measure deficiency status separately in participants with functional impairment, and distinguish results for those requiring correction from those receiving additional supplementation." }, { "item_id": "N06", "question_type": "Molecular form and route", "question": "Were the salts and routes of ordinary thiamine accurately distinguished?", "needed": "Link the exact salt, number of active ingredients, formulation and route to the reasons for excluding other forms. Required source materials: Product ingredient lists, manufacturing/batch documents and records of the formulation and route administered in the study.", "role": "Required", "role_reason": "This is needed to avoid incorrectly merging exposure identities and result attribution.", "application_exception": "Retain evidence on derivatives, combinations and injections, but do not promote it to direct results for single-ingredient oral ordinary thiamine.", "criterion": "Link the exact salt, number of active ingredients, formulation and route to the reasons for excluding other forms.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed — this is an item-specific adaptation for molecular form and route, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Fix each formulation's identity and extract results for single-active-ingredient oral exposure separately." }, { "item_id": "N07", "question_type": "Dose and schedule", "question": "Were nominal dose, actual dose and thiamine-equivalent amount verified?", "needed": "Distinguish the extent to which the eligible preparation's nominal dose for 1 time/daily dose, actual exposure, equivalent amount and administration schedule have been verified. Required source materials: Administration logs, medication/ingredient documents, count/adherence records and the basis for the stated equivalent amount.", "role": "Required", "role_reason": "This is a required criterion for exposing gaps in dose identity and actual exposure.", "application_exception": "Do not designate another study's nominal dose as the optimal dose or minimum effective dose.", "criterion": "Distinguish the extent to which the eligible preparation's nominal dose for 1 time/daily dose, actual exposure, equivalent amount and administration schedule have been verified.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are internally designed — this is an item-specific adaptation for dose and schedule, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Record planned doses and actual administered doses separately in a single-ingredient comparison, and examine the relationship between adherence and the analysis population." }, { "item_id": "N08", "question_type": "Treatment and measurement times", "question": "Were treatment duration and the principal gait-speed measurement time point verified?", "needed": "State separately the actual extent of verification of treatment duration, the principal measurement time point and additional follow-up. Required source materials: Protocol schedule, actual administration/visit dates and the analysis plan for the principal time point.", "role": "Required", "role_reason": "This is needed to prevent automatic substitution of durations and effect-observation times.", "application_exception": "Do not require every form of long-term follow-up for the original question; review long-term maintenance separately if that claim is added.", "criterion": "State separately the actual extent of verification of treatment duration, the principal measurement time point and additional follow-up.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are internally designed — this is an item-specific adaptation for treatment and measurement times, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Fix treatment and measurement schedules separately, distinguishing final values, changes and post-discontinuation results in advance." }, { "item_id": "N09", "question_type": "Comparator and concomitant care", "question": "How did care other than thiamine actually differ?", "needed": "Separate between-arm intervention differences, shared care, deviations/rescue and the effect of interest. Required source materials: Arm-specific concomitant-treatment/change tables, diet and rehabilitation plans, and records of rescue treatment/dropout handling.", "role": "Required", "role_reason": "This criterion prevents attributing the contribution of a multicomponent formula or concomitant treatment to thiamine alone.", "application_exception": "Do not require complete identity of every individual change; verify the actual effect of interest and how changes are handled.", "criterion": "Separate between-arm intervention differences, shared care, deviations/rescue and the effect of interest.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application — this is an item-specific adaptation for comparator and concomitant care, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Specify the care shared by the arms, record actual changes and adherence, and link the intervention contrast of interest to the effect analyzed." }, { "item_id": "N10", "question_type": "Comparative design", "question": "Were allocation, blinding and analysis design for the direct gait-speed comparison verified?", "needed": "Link actual allocation, design and analysis information relevant to the selected result to verified source locations. Required source materials: Original methods, protocol, allocation records, baseline tables and analysis plan.", "role": "Required", "role_reason": "This is needed to distinguish the actual comparative design required for efficacy from design information in indirect studies.", "application_exception": "Retain nonrandomized data as well, but label their design limitations and do not promote them to an RCT of causal efficacy.", "criterion": "Link actual allocation, design and analysis information relevant to the selected result to verified source locations.", "basis": "M08 §8.1–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; M03 §3.2.1; detailed population criteria are internally designed — this is an item-specific adaptation for comparative design, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Select an eligible comparison first, then examine actual limitations in allocation, measurement, missing data and analysis for each gait-speed result of interest." }, { "item_id": "N11", "question_type": "Gait measurement", "question": "Was the actual testing procedure for usual gait speed verified?", "needed": "Link the actual test conditions required for usual gait speed to the reasons for excluding other functional endpoints. Required source materials: Test SOP, original gait-measurement tables, assessor/device records, protocol and arm-specific implementation information.", "role": "Required", "role_reason": "This is needed to distinguish similar functional-scale names from actual measurement of the same outcome.", "application_exception": "Do not automatically treat inability to blind as failure; verify limitations in the actual measurement procedures.", "criterion": "Link the actual test conditions required for usual gait speed to the reasons for excluding other functional endpoints.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4; internally defined extension boundaries — this is an item-specific adaptation for gait measurement, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Fix usual-speed instructions and distance/start conditions, and consistently record repeated measurements, assistive devices and assessor conditions." }, { "item_id": "N12", "question_type": "Effect definition", "question": "Were the between-group effect, final values and changes verified?", "needed": "Attribute the original result's between-group/within-group contrast, final value/change and analysis/adjustment to the corresponding endpoint and time point. Required source materials: Result tables, analysis plan, model output, ITT/PP definitions and prespecified primary contrasts.", "role": "Required", "role_reason": "This is needed to avoid confusing values from different analyses with the intended causal contrast.", "application_exception": "If the source does not specify the analysis, do not arbitrarily label it ITT or an adjusted effect.", "criterion": "Attribute the original result's between-group/within-group contrast, final value/change and analysis/adjustment to the corresponding endpoint and time point.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed — this is an item-specific adaptation for effect definition, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Link the between-group gait-speed contrast at the defined principal time point to the analysis population/model, and report it separately from within-group changes." }, { "item_id": "N13", "question_type": "Denominators and losses", "question": "Can the numbers allocated, completing and analyzed be distinguished from missing data?", "needed": "Link allocation, completion, analysis and arm-specific/outcome-specific denominators to the corresponding time points. Required source materials: Participant flow diagram, outcome-specific n, reasons for dropout/measurement failure and the handling plan.", "role": "Required", "role_reason": "This is needed to avoid incorrectly relabeling retained sample sizes as outcome-specific analysis denominators.", "application_exception": "Do not calculate unavailable dropout counts, denominators or CIs, or treat crossover observations as unique participants.", "criterion": "Link allocation, completion, analysis and arm-specific/outcome-specific denominators to the corresponding time points.", "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; M08 §8.1–8.2.3; internal application — this is an item-specific adaptation for denominators and losses, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Trace the flow from allocation to gait measurement and analysis, and examine the effects of missingness reasons and handling for each analysis population." }, { "item_id": "N14", "question_type": "Intervals and importance", "question": "Were the CI and a clinically important difference verified?", "needed": "Link the type of interval in the original report and the basis for importance only to the extent verified. Required source materials: Eligible estimates/CIs, variance types, denominators, the basis for clinical importance and a prespecified interpretation plan.", "role": "Required", "role_reason": "This is needed to distinguish significance and sample size from precision and clinical meaning.", "application_exception": "Do not invent new MCIDs, CIs, variances or sample sizes without a basis, or convert IQR/SD/SE into an interval.", "criterion": "Link the type of interval in the original report and the basis for importance only to the extent verified.", "basis": "M15 §15.3.1–15.3.3; internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed — this is an item-specific adaptation for intervals and importance, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Report CIs linked to their original estimates and denominators/variances, explaining separately the basis for applying an importance criterion and what remains unverified." }, { "item_id": "N15", "question_type": "Planning and registration", "question": "Were the primary gait endpoint and planned analysis compared with the actual registration?", "needed": "Distinguish the level of plans/registration obtained, the parts not actually compared and the reasons for changes. Required source materials: Eligible original registry history, protocol, SAP, endpoint/analysis change records and reported results.", "role": "Required", "role_reason": "This criterion reveals the extent to which planned outcomes can be compared with selective reporting of favorable results.", "application_exception": "Do not treat publication of a related trial's protocol as verification of preregistration for the target comparison.", "criterion": "Distinguish the level of plans/registration obtained, the parts not actually compared and the reasons for changes.", "basis": "M08 Table 8.2.a, M04 §4.6.3; internal application; M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limitations on the current material conversion follow the user-defined scope and internal design — this is an item-specific adaptation for planning and registration, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Compare planned gait endpoints, time points and analyses against initial and amended versions and actual reports, retaining the extent of discrepancies and their reasons." }, { "item_id": "N16", "question_type": "Study families", "question": "Were reports from the same study distinguished from direct independent replication?", "needed": "Link same/different/uncertain families to their original locations, leaving replication and unique-participant counts unresolved where unconfirmed. Required source materials: Report-registration-cohort linkage tables, directly eligible criteria/result tables and materials for identifying overlap.", "role": "Required", "role_reason": "This criterion distinguishes the number of reports from the number of direct independent comparisons.", "application_exception": "Do not erase unresolved candidates as not applicable, or count the same 24 HF participants as 4 studies or 48 people.", "criterion": "Link same/different/uncertain families to their original locations, leaving replication and unique-participant counts unresolved where unconfirmed.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed — this is an item-specific adaptation for study families, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Link reports to unique studies first, and compare only independent results verified to match in population, preparation, measure and time point." }, { "item_id": "N17", "question_type": "Funding and conflicts of interest", "question": "Does funding of indirect studies establish independence of the target efficacy evidence?", "needed": "Link the reported level of funding/conflict information, unverified information and applicability limitations to each study. Required source materials: Each study's original Funding/COI sections, provision/institution/employment documents and relationships among reports in the family.", "role": "Supplementary; required for independence claims", "role_reason": "This supplementary criterion prevents automatic inheritance of indirect studies' funding into the target efficacy axis.", "application_exception": "Do not automatically exclude a study because of a conflict of interest, or establish the absence of conflicts from a missing declaration.", "criterion": "Link the reported level of funding/conflict information, unverified information and applicability limitations to each study.", "basis": "Chamgap's own independence/attribution criteria. The official methodological sections used in this pilot do not guarantee all of these detailed items; M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application — this is an item-specific adaptation for funding and conflicts of interest, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Extract study-specific funding, product provision and declared conflicts separately from results, and compare them with the scope of independence claims." }, { "item_id": "N18", "question_type": "HF exposure and population", "question": "Does the single-ingredient oral trial in older HF patients match the target population?", "needed": "Distinguish the actual HF population, regimen and selection restrictions from the target population/exposure. Required source materials: Original HF methods, selection/baseline tables, formulation/administration records, adherence and original supplements.", "role": "Supplementary; required for attribution of indirect materials", "role_reason": "This is needed to preserve both what is known from closely related single-ingredient oral evidence and its gaps in directness.", "application_exception": "Do not generalize to all vulnerable older adults by omitting exclusions for dialysis/symptomatic deficiency or conditions involving caregiver assistance.", "criterion": "Distinguish the actual HF population, regimen and selection restrictions from the target population/exposure.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — this is an item-specific adaptation for HF exposure and population, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Link population, salt, route, adherence and exclusion criteria to the eligibility table, specifying differences from the target question." }, { "item_id": "N19", "question_type": "HF outcome boundaries", "question": "Were HF results showing no difference or unfavorable effects kept from being transferred to gait speed?", "needed": "Preserve the direction of other HF results and the absence of target gait results without conflating them. Required source materials: Original HF result tables, endpoint definitions, each analysis/denominator and the relevant location if a gait endpoint has been newly reported.", "role": "Supplementary; required for boundaries on transferring results", "role_reason": "This boundary criterion preserves contrary results and prevents automatic substitution of endpoints.", "application_exception": "Do not create a gait effect by selecting favorable results for other outcomes or deleting unfavorable results for other outcomes.", "criterion": "Preserve the direction of other HF results and the absence of target gait results without conflating them.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M03 §3.2.4; internally defined extension boundaries — this is an item-specific adaptation for HF outcome boundaries, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Attribute each endpoint's results to its definition, time point and denominator, and construct a table of directness for the target question." }, { "item_id": "N20", "question_type": "HF reporting discrepancies", "question": "Was the scope of discrepancies among abstracts, final reports and totals preserved?", "needed": "Retain the locations of actual recorded discrepancies together with unchecked details and explanations of versions/denominators. Required source materials: Original conference abstract, final original tables, adherence definitions, supplements/corrections and registry history.", "role": "Supplementary; required for handling conflicting information", "role_reason": "This is needed to limit the scope of conflicts, overlap and selective reporting to the relevant reports.", "application_exception": "Do not create additional conflicts solely from numerical differences across definitions/time points, or average original values together.", "criterion": "Retain the locations of actual recorded discrepancies together with unchecked details and explanations of versions/denominators.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application — this is an item-specific adaptation for HF reporting discrepancies, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Compare report versions from the same cohort using the same definitions/denominators, distinguishing resolved differences from remaining conflicts." }, { "item_id": "N21", "question_type": "CKD multicomponent exposure", "question": "Can the CKD formula's gait results be attributed to B1 alone?", "needed": "Verify the actual formula, diet and comparison, and that individual component contributions have not been separated. Required source materials: Product ingredient lists, original administration/diet plans, actual intake and component-specific contrast data.", "role": "Supplementary; required for attribution of combination-product results", "role_reason": "This attribution criterion prevents a positive multicomponent-exposure result from erasing gaps in the single-ingredient B1 question.", "application_exception": "Preserving the combined effect does not mean deleting it or declaring it invalid, and it is not promoted to direct evidence for the target single ingredient.", "criterion": "Verify the actual formula, diet and comparison, and that individual component contributions have not been separated.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed — this is an item-specific adaptation for CKD multicomponent exposure, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "If B1's contribution is the question, design a separate single-ingredient add-on contrast with other care matched, while retaining the formula results." }, { "item_id": "N22", "question_type": "Attribution of CKD numerical values", "question": "Were medians, IQRs and within-group/between-group P values distinguished?", "needed": "Preserve the median, IQR and the hypothesis tested by each P value, leaving unverified between-group estimates unverified. Required source materials: Original result Table 3, models/tests, arm-specific change distributions and between-group estimates/CIs.", "role": "Supplementary; required for numerical attribution", "role_reason": "This criterion prevents attributing positive numerical results to the wrong ingredient, comparison or interval.", "application_exception": "Do not use arithmetic in this review to create an unavailable between-group magnitude or CI, or read an IQR as a precision interval.", "criterion": "Preserve the median, IQR and the hypothesis tested by each P value, leaving unverified between-group estimates unverified.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application — this is an item-specific adaptation for attribution of CKD numerical values, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Compare the arm-specific medians/distributions and the analysis definition of the between-group change test against the original table, explaining component attribution separately from the statistical contrast." }, { "item_id": "N23", "question_type": "CKD testing and denominators", "question": "Were actual CKD gait testing and the analysis population distinguished?", "needed": "Link CKD allocation/analysis flow and test conditions to differences from the target selection criteria. Required source materials: Baseline/selection tables, participant flow, gait SOP and outcome-specific analysis/missingness tables.", "role": "Supplementary; required for applicability/denominators", "role_reason": "This criterion accurately preserves the populations, tests and denominators behind the formula's numerical results.", "application_exception": "Do not establish functional impairment from a CKD diagnosis or age alone, or guarantee that the overall analysis n is the n for every test.", "criterion": "Link CKD allocation/analysis flow and test conditions to differences from the target selection criteria.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application — this is an item-specific adaptation for CKD testing and denominators, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Compare participant flow and measurement procedures for each outcome to limit the applicability of the formula results." }, { "item_id": "N24", "question_type": "CKD registration notation", "question": "Were registration-date conflicts distinguished from original tables not compared?", "needed": "Separate the record of conflicting registration-date notation from the scope of original tables/registration not compared. Required source materials: Initial/amended registry history, original registration-date sections, Table 2/3 and explanations of corrections.", "role": "Supplementary; required for registration/conflicts", "role_reason": "This criterion retains historical access limitations and actual reported conflicts within their precise scope.", "application_exception": "Do not label a current lack of attempt as a current access failure, or automatically fill detailed dates from other files.", "criterion": "Separate the record of conflicting registration-date notation from the scope of original tables/registration not compared.", "basis": "M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application — this is an item-specific adaptation for CKD registration notation, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Compare the meaning and version of registration dates with the source materials, recording main-text/table access limitations alongside the scope of numerical extraction." }, { "item_id": "N25", "question_type": "Nursing-home observations", "question": "Was the observed direction for deficiency and ability to walk kept from being reversed into a supplementation effect?", "needed": "Accurately preserve the observational population, deficiency/feeding routes, walking denominators and causal limitations. Required source materials: Original Table 2/3, feeding route/care level/walking denominators, design and adjustment data.", "role": "Supplementary; required for attribution of observations", "role_reason": "This criterion prevents reversing deficiency associations into treatment directions or mixing denominators.", "application_exception": "Do not convert ability to walk into speed, or treat tube/intravenous feeding in the nondeficient group as an oral B1 intervention.", "criterion": "Accurately preserve the observational population, deficiency/feeding routes, walking denominators and causal limitations.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M08 §8.1–8.2.3; internal application; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application — this is an item-specific adaptation for nursing-home observations, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Compare the observational definitions of exposure and outcome with feeding route/care selection, distinguishing them from a separate question about assigned treatment." }, { "item_id": "N26", "question_type": "Inpatient functional observations", "question": "Was Barthel recovery distinguished from a treatment effect on gait speed?", "needed": "Attribute the inpatient observation's scale, population, nutritional markers and material-access level to its own result. Required source materials: Original methods/results, marker criteria, adjustment, functional-recovery tables and an eligible comparison.", "role": "Supplementary; required for attribution of observations", "role_reason": "This criterion prevents an observed result for another form of functional recovery from substituting for target efficacy.", "application_exception": "Do not generalize the abstract's association or 0 deficiency cases into an oral B1 treatment effect or to all nondeficient older adults.", "criterion": "Attribute the inpatient observation's scale, population, nutritional markers and material-access level to its own result.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.1–8.2.3; internal application; M03 §3.2.4; internally defined extension boundaries — this is an item-specific adaptation for inpatient functional observations, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Link the Barthel association to exposure, time and confounding, and assess it separately from the causal gait-speed question." }, { "item_id": "N27", "question_type": "Observations on other B vitamins", "question": "Do dietary data on other B vitamins answer the B1 functional-impairment question?", "needed": "Identify differences in B6/B12/folate exposure, a population with unimpaired function and self-reported outcomes. Required source materials: Original exposure, selection/baseline function, measure definitions and an eligible B1 comparison.", "role": "Supplementary; required for boundaries concerning other nutrients", "role_reason": "This criterion keeps the presence or absence of positive findings for other ingredients/observational questions from erasing the direct B1 evidence gap.", "application_exception": "Do not promote an indexed abstract to newly read full text or record it as a successful current PubMed search.", "criterion": "Identify differences in B6/B12/folate exposure, a population with unimpaired function and self-reported outcomes.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.1–8.2.3; internal application — this is an item-specific adaptation for observations on other B vitamins, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Extract differences in each nutrient and functional definition, indicating relevance without pooling them as causal B1 effects." }, { "item_id": "N28", "question_type": "Registry candidates", "question": "Were the composition, population and results of registry leads actually verified?", "needed": "Record each of the two candidates' verified identities and unresolved composition, eligibility and results separately. Required source materials: Original structured registry content, amendment history, protocol and linked result reports.", "role": "Supplementary; required for candidate eligibility", "role_reason": "This criterion separates the existence of a candidate from acquisition of efficacy results.", "application_exception": "Do not replace an unresolved candidate with confirmed exclusion from eligibility, an effect of 0 or not applicable.", "criterion": "Record each of the two candidates' verified identities and unresolved composition, eligibility and results separately.", "basis": "M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application — this is an item-specific adaptation for registry candidates, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Check exposure/population/outcome eligibility for each candidate first, linking it to a family only when a result is verified." }, { "item_id": "N29", "question_type": "Grip-strength trial in deficiency", "question": "Was Wilkinson's deficiency/grip-strength trial kept from being transferred to gait speed?", "needed": "Limit deficiency selection, grip strength and the oral regimen to the relevant family and extraction level. Required source materials: Original eligibility/administration, grip and gait measurements/results, and exact-salt data.", "role": "Supplementary; required for attribution of prior extractions", "role_reason": "This criterion clarifies reuse of prior extractions and attribution to a different distinct claim.", "application_exception": "Do not inherit a previous verdict/score or a dose for another endpoint as fulfillment of new gait-speed criteria.", "criterion": "Limit deficiency selection, grip strength and the oral regimen to the relevant family and extraction level.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed — this is an item-specific adaptation for grip-strength trial in deficiency, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Compare the questions and measures in the prior extraction and original report, but reconsider separate eligibility only if a gait result was actually reported." }, { "item_id": "N30", "question_type": "IBD fatigue trial", "question": "Is the TARIF fatigue trial a gait-speed comparison in older adults?", "needed": "Distinguish TARIF's population/results and the original extraction level from the gait-speed question. Required source materials: Original population, endpoint/analysis tables, exposure form and eligible gait results.", "role": "Supplementary; required for boundaries concerning other endpoints", "role_reason": "This criterion separates the different population and endpoint of a closely related oral trial.", "application_exception": "Do not adopt a previous fatigue verdict or another endpoint's results as a new direct gait-speed effect.", "criterion": "Distinguish TARIF's population/results and the original extraction level from the gait-speed question.", "basis": "M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed — this is an item-specific adaptation for IBD fatigue trial, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Attribute results to their respective questions using an eligibility table that distinguishes disease-related fatigue, grip strength and gait." }, { "item_id": "N31", "question_type": "Trial in healthy older adults", "question": "Was Smidt's healthy/marginal-deficiency population kept separate from the target population?", "needed": "Link the applicability limitations concerning healthy women, marginal deficiency and unverified function/gait. Required source materials: Original selection, sex/baseline status, administration and actual functional-measurement/analysis tables.", "role": "Supplementary; required for population boundaries", "role_reason": "This criterion prevents expanding population directness based on the label older adults.", "application_exception": "Do not reclassify a study of healthy older adults as a study of objective functional impairment.", "criterion": "Link the applicability limitations concerning healthy women, marginal deficiency and unverified function/gait.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed — this is an item-specific adaptation for trial in healthy older adults, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Distinguish health/functional-impairment and deficiency criteria, and compare direct-gait-comparison eligibility with the original results." }, { "item_id": "N32", "question_type": "CMT mixed-form observations", "question": "Were uncontrolled mixed-form CMT data kept from being promoted to direct results?", "needed": "Preserve boundaries concerning mixed forms/ages, lack of controls, correction extractions and unverified target results. Required source materials: Original observations/corrections, individual forms/routes/ages, gait results and comparative data.", "role": "Supplementary; required for attribution of mixed observations", "role_reason": "This criterion prevents overinterpretation of mixed uncontrolled observations and original corrections.", "application_exception": "Do not label an error resolved merely because metadata indicate a correction, or combine derivative effects as ordinary-thiamine effects.", "criterion": "Preserve boundaries concerning mixed forms/ages, lack of controls, correction extractions and unverified target results.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.1–8.2.3; internal application; M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed — this is an item-specific adaptation for CMT mixed-form observations, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Separate form/population/route and the content before and after the original correction, examining applicability to the gait comparison." }, { "item_id": "N33", "question_type": "Deficiency neuropathy", "question": "Was FIM functional improvement kept from being relabeled as usual gait speed?", "needed": "Separate FIM, deficiency neuropathy and treatment extractions from a direct gait-speed comparison. Required source materials: Original population, administration/route, FIM/gait measurement, comparator and results by time point.", "role": "Supplementary; required for scale boundaries", "role_reason": "This criterion prevents automatically exchanging outcomes because functional scales use similar wording.", "application_exception": "Do not generalize the need to correct deficiency or FIM improvement into a gait effect in nondeficient older adults.", "criterion": "Separate FIM, deficiency neuropathy and treatment extractions from a direct gait-speed comparison.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.1–8.2.3; internal application; M03 §3.2.4; internally defined extension boundaries; M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed — this is an item-specific adaptation for deficiency neuropathy, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Attribute deficiency-treatment scales and exposures to their original reports, examining separately whether a target gait comparison is established." }, { "item_id": "N34", "question_type": "Injection case reports", "question": "Are intramuscular observations in muscular dystrophy oral-comparison data?", "needed": "Identify differences between intramuscular case reports and single-ingredient oral gait comparisons. Required source materials: Original case diseases, routes/preparations, time points/function definitions and an eligible oral comparison.", "role": "Supplementary; required for route boundaries", "role_reason": "This criterion prevents overstepping disease/route/design boundaries and falsely promoting the existence of a link.", "application_exception": "Do not convert a public PMC URL into a badge of current full-text reading or a result for an oral preparation.", "criterion": "Identify differences between intramuscular case reports and single-ingredient oral gait comparisons.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.1–8.2.3; internal application; M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed — this is an item-specific adaptation for injection case reports, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Separate results by route and disease, distinguishing case observations from effect estimates in controlled trials." }, { "item_id": "N35", "question_type": "Direct harm-data gap", "question": "Were adverse events/discontinuations in the same population and regimen verified?", "needed": "Separate collection methods, denominators, duration and unverified scope for direct harms/discontinuations. Required source materials: AE/discontinuation tables for the same population/preparation, exposure/follow-up flow, collection methods and original event records.", "role": "Supplementary; required for the relevant harm/safety claims", "role_reason": "This supplementary criterion displays the efficacy gap separately from the gap in direct safety data.", "application_exception": "Do not delete indirect efficacy sources because of a harm-data gap, or automatically assign the same status as the efficacy criteria.", "criterion": "Separate collection methods, denominators, duration and unverified scope for direct harms/discontinuations.", "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, M04 §4.6.3; internal application — this is an item-specific adaptation for direct harm-data gap, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Plan harm collection separately within an eligible efficacy comparison, reporting events, people, exposure periods and discontinuation reasons distinctly." }, { "item_id": "N36", "question_type": "HF harm signal", "question": "Were diarrhea improvement after discontinuation and event totals kept from being converted into risk estimates?", "needed": "Preserve the 1 diarrhea event, improvement after discontinuation and original discrepancies in totals at the level of the report. Required source materials: Original HF AE/SAE tables, original discontinuation records, exposure by arm/period, alternative causes and correction materials.", "role": "Supplementary; required for attribution of harm signals", "role_reason": "This criterion is needed to preserve harm signals while preventing their promotion to incidence or causality.", "application_exception": "Do not automatically use all 24 randomized participants or the 19 completers as AE denominators, or correct table totals through new calculations.", "criterion": "Preserve the 1 diarrhea event, improvement after discontinuation and original discrepancies in totals at the level of the report.", "basis": "M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed distinctions are internally designed; M19 §19.2 design-specific harm questions; temporal-relationship details are internally designed; M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed; Chamgap's own interpretation boundaries. M19 principles are referenced; no official causality tool is implemented; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed — this is an item-specific adaptation for HF harm signal, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Compare the original event's timing, discontinuation, alternative explanations and event/person totals, distinguishing signals, comparative risk and causal statements." }, { "item_id": "N37", "question_type": "Official product-information boundaries", "question": "Were the absence of a UL and product wording kept from becoming a general safety guarantee?", "needed": "Distinguish the absence of a UL, product-specific salts/wording, route-specific risks and current non-reading. Required source materials: Exact ingredients/excipients of the relevant study product, product-information versions and original harm data for the same route/population.", "role": "Supplementary; required for safety-interpretation boundaries", "role_reason": "This criterion prevents mistaking the existence of an official fact sheet/label for established efficacy or safety, or for identity of products.", "application_exception": "Do not transfer oral-product-specific pregnancy/lactation or excipient cautions to all nutritional exposures/other salts.", "criterion": "Distinguish the absence of a UL, product-specific salts/wording, route-specific risks and current non-reading.", "basis": "M19 §19.1.2–19.2.4; internal application; M03 §3.2.2–3.2.3; reverse-direction labeling and testing adaptations are internally designed; M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; Chamgap's own interpretation boundaries. M19 principles are referenced; no official causality tool is implemented — this is an item-specific adaptation for official product-information boundaries, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Compare applicability by product/route/dose, separating official wording from actually collected events and frequencies." }, { "item_id": "N38", "question_type": "Vulnerable groups and refeeding", "question": "Were the limited HF/refeeding contexts kept from being applied to all older adults?", "needed": "Distinguish original exclusions/vulnerable groups and the purpose of refeeding from direct/long-term safety gaps. Required source materials: Vulnerable-group selection/exposure, concomitant medications, long-term follow-up/harm data and the exact refeeding-guideline version.", "role": "Supplementary; required for vulnerable-group/long-term safety claims", "role_reason": "This supplementary criterion prevents generalizing safety from selected populations or exceeding the scope of clinically supervised contexts.", "application_exception": "Do not require every rare-harm study for the current narrow gait-speed question, or convert refeeding wording into a personal prescription.", "criterion": "Distinguish original exclusions/vulnerable groups and the purpose of refeeding from direct/long-term safety gaps.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M19 §19.1.2–19.2.4; internal application; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are internally designed — this is an item-specific adaptation for vulnerable groups and refeeding, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Link population-specific exclusions and clinical-supervision purposes to the eligibility table; if long-term/vulnerable-group claims are needed, review materials within those scopes separately." }, { "item_id": "N39", "question_type": "Extended applicability", "question": "Were falls, optimal dose and maintained effects made mandatory parts of the gait-speed question?", "needed": "Clarify why separate questions about events, dose and maintained effects do not apply as conditions for the gait-speed result. Required source materials: The exact original wording of the extended claim, relevant event/dose/follow-up comparisons and results.", "role": "Supplementary; required for the relevant extended claims", "role_reason": "This supplementary criterion separates requirements for the narrow subject of the verdict from separate extension criteria.", "application_exception": "Do not require an event trial for the numerical-change question itself; keep unresolved candidate/eligible materials unverified in other rows.", "criterion": "Clarify why separate questions about events, dose and maintained effects do not apply as conditions for the gait-speed result.", "basis": "M03 §3.2.1–3.2.4; dose, duration and effect-modification details are internally designed; M03 §3.2.4; internally defined extension boundaries; M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed — this is an item-specific adaptation for extended applicability, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "If an extension is requested, first establish the distinct question boundary, then review direct results separately from the existing gait-speed table." }, { "item_id": "N40", "question_type": "Original verdict and history", "question": "Were ?/null, the calculation exception, document quality and historical deployment distinguished?", "needed": "Separate the original ?/null, unscored axes, invalid suggestion, document self-assessment and historical deployment from what was produced in this review. Required source materials: Original verdict/calculation-exception records, identity/deployment history, authorized change decisions and complete versions before and after changes.", "role": "Required", "role_reason": "This is a required preservation criterion to prevent automatic inheritance of scores/statuses or historical completion metadata.", "application_exception": "Do not use general code-structure checks as a new clinical score, implementation of an official method or certification of study absence.", "criterion": "Separate the original ?/null, unscored axes, invalid suggestion, document self-assessment and historical deployment from what was produced in this review.", "basis": "M04 §4.5, §4.6.3; limitations on the current material conversion follow the user-defined scope and internal design; M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed — this is an item-specific adaptation for original verdict and history, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "Record verdict, document, calculation and publication events separately; if subsequent evidence is authorized, review any change to the current value through a separate process." }, { "item_id": "N41", "question_type": "Historical local documents", "question": "Were S20/S21 kept from being labeled as rule files read in this review?", "needed": "Separate historical reading of S20/S21 from reading their bibliographic summaries and not reading the source documents in this review. Required source materials: Historical local source documents, versions, bytes/SHA and application/access records from the time.", "role": "Supplementary; required for tracing local materials", "role_reason": "This traceability criterion distinguishes current summary access from source-document access for local rule documents as well.", "application_exception": "Do not create current file links from original relative paths without safe actual files, or count them as external clinical results.", "criterion": "Separate historical reading of S20/S21 from reading their bibliographic summaries and not reading the source documents in this review.", "basis": "M04 §4.5–4.6 data-collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limitations on the current material conversion follow the user-defined scope and internal design — this is an item-specific adaptation for historical local documents, not implementation/certification of an official method.", "condition_origin": "Development criteria individually designed with knowledge of the current retained content for 3118. Neither blinded nor preregistered.", "proposed_research": "If separate verification is needed, first check actual file identity, distinguishing historical application from access events in this review." } ] }