{ "schema_version": "chamgap-public-criteria-1.0", "title": "Topical berberine gelatin 5 mg/g × Reduction of pain from minor recurrent aphthous ulcers", "language": "en", "translation_date": "2026-10-27", "criteria_version": "1.0", "criteria_date": "2026-10-05", "condition_origin": "Chamgap's own application conditions", "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": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "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": "Link studies and reports separately; do not omit studies solely because results are unreported.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "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 result and effect of interest when examining randomization, deviations, missingness, measurement and selective reporting.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "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": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "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 different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." } ], "status_dictionary": { "Met": "The row’s narrow record, attribution, boundary or actual fact was checked. This does not certify efficacy, precision or safety.", "Partly verified": "Some required information is available, but actual exposure, definitions, denominators or other necessary material remain missing.", "Unverified": "The criterion cannot be established within the retained scope. This does not mean 0 effect, 0 studies or failed access.", "Not applicable": "Used only with a reason that an item is outside the actual scope of the selected question. It does not replace unverified or unread status.", "Not reported": "Nonreporting is limited to a specific material or section actually read. This work did not assign a reporting status to the entire full paper.", "Inaccessible": "Used only for an actual access failure. Distinguish it from external access not attempted in this work." }, "requirements": [ { "item_id": "N01", "question_type": "Evidence condition", "question": "Which topical formulation, population and pain comparison does this checklist address?", "needed": "Fixed identity of the original claim, application site/formulation/route, population, comparator, pain outcome and time.", "role": "Required (claim identity)", "role_reason": "The ingredient name alone does not justify combining oral use or other ulcer outcomes.", "application_exception": "Do not automatically create separate new efficacy cases for pain, size, erythema and exudation.", "criterion": "Link the original claim and exclusion boundaries for 5 mg/g berberine gelatin applied topically to oral ulcers in adults with minor recurrent aphthous disease, over 5 days, for pain versus vehicle.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare the actual intervention, population, outcome, comparator and time in subsequent documents with this question." }, { "item_id": "N02", "question_type": "Evidence condition", "question": "Are diagnosis, eligibility and baseline characteristics of minor recurrent aphthous stomatitis verified?", "needed": "Diagnostic criteria, age, baseline ulcer/pain values, eligibility criteria and characteristics by arm.", "role": "Required (population directness)", "role_reason": "Do not transfer the findings to oral ulcers of other causes, severe disease or children.", "application_exception": "Unverified eligibility criteria do not establish lack of effect in other diseases.", "criterion": "Check the adult/minor recurrent aphthous population record against actual diagnostic methods, age, eligibility criteria and baseline ulcer/pain data.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link eligibility criteria and baseline tables to examine whether the actual analysis population comprises adults with minor recurrent aphthous disease." }, { "item_id": "N03", "question_type": "Evidence condition", "question": "Are the actual batch, composition and manufacturing specifications of purified berberine 5 mg/g gelatin verified?", "needed": "Trial-product composition, batch, salt form, manufacturing/assay records and vehicle composition.", "role": "Required (intervention identity)", "role_reason": "Do not treat botanical extracts, berberine hydrochloride tablets or derivatives as the same trial product.", "application_exception": "Do not fill the unverified plant source with an invented plant species or another salt specification.", "criterion": "Compare the retained 5 mg/g berberine-gelatin, purified-ingredient and topical-route record with actual batch/salt form/vehicle composition and manufacturing specifications.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link product/batch documents to the actual trial product to check agreement in ingredient concentration and gelatin composition." }, { "item_id": "N04", "question_type": "Evidence condition", "question": "Are actual amount, adherence and swallowed exposure with 4 daily applications verified?", "needed": "Amount per application, use records, returns/adherence and swallowed/retained exposure.", "role": "Required (actual exposure)", "role_reason": "Do not convert the 5 mg/g concentration into a total daily dose or systemic absorption.", "application_exception": "Verification of nominal frequency does not establish an optimal application amount or a safe amount to swallow.", "criterion": "Check the nominal frequency of 4 daily applications against actual gelatin amount per application, adherence and retention/swallowing measurements.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link use records and administration procedures to distinguish nominal frequency from actual local exposure. Do not convert concentration into a systemic dose." }, { "item_id": "N05", "question_type": "Evidence condition", "question": "Are vehicle composition, matching appearance and additional treatment by arm verified?", "needed": "Comparator composition/appearance, concomitant oral treatment, rescue medication and changes by arm.", "role": "Required (intervention contribution)", "role_reason": "Do not attribute vehicle effects or differences in additional treatment to berberine.", "application_exception": "The existence of a vehicle comparator does not establish that all co-interventions were identical.", "criterion": "Check the vehicle-gelatin comparator without berberine against actual composition/appearance, additional oral care and rescue-treatment material by arm.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare the vehicle product and additional treatment by arm with intervention-product/adherence records to examine differences beyond the selected ingredient." }, { "item_id": "N06", "question_type": "Evidence condition", "question": "Were the original treatment and assessment time boundaries distinguished?", "needed": "Original records of treatment duration, assessment days and end of follow-up.", "role": "Required (time identity)", "role_reason": "Do not turn 5-day treatment into identical analysis across all assessment days or a long-term effect.", "application_exception": "Actual time-specific analyses remain unverified in other rows.", "criterion": "Distinguish the original record of 5-day application from assessments on days 1, 2, 4 and 6; do not add claims that actual results/denominators at each assessment were verified.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link subsequent schedules and result tables to distinguish application duration from measurement days and attribute only verified results to their assessment times." }, { "item_id": "N07", "question_type": "Evidence condition", "question": "Are random-sequence generation, allocation concealment and baseline balance verified?", "needed": "Sequence generation, allocation concealment, recruitment/allocation procedures and baseline tables.", "role": "Required (causal comparison)", "role_reason": "A randomized-trial label alone does not resolve allocation bias or baseline differences.", "application_exception": "Do not arbitrarily relabel the design as nonrandomized because allocation details remain unverified.", "criterion": "Check the randomized vehicle-trial record against actual sequence generation, concealment and baseline-balance material by arm.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link methods/allocation records to baseline tables to examine the actual allocation process and its unverified elements." }, { "item_id": "N08", "question_type": "Evidence condition", "question": "Whose masking and its actual maintenance are verified?", "needed": "Masking targets, product distinguishability, maintenance/testing and analyst procedures.", "role": "Required (subjective pain assessment)", "role_reason": "Do not extend the term double-blind to masking of every assessor and analyst.", "application_exception": "Unverified masking does not automatically negate the pain effect.", "criterion": "Check the double-blind record against actual masking targets among participants, clinicians, assessors and analysts, and material on maintenance/testing.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link methods and formulation-comparison material to examine the verified scope of actual masking targets and maintenance." }, { "item_id": "N09", "question_type": "Evidence condition", "question": "Are the pain scale, range, direction and collection method verified?", "needed": "Scale name/range/units, assessors, collection procedures and time-specific result tables.", "role": "Required (outcome measurement)", "role_reason": "Do not invent an exact VAS difference without a scale definition.", "application_exception": "Do not substitute ulcer size or healing duration for the pain score.", "criterion": "Check pain VAS/score against the actual scale range, direction, assessors, collection timing/method and measurement conditions by arm.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link the scale description and each result table to compare pain variables/units, the meaning of lower scores and agreement in assessment conditions." }, { "item_id": "N10", "question_type": "Evidence condition", "question": "Are analgesics, oral treatment and handling of adherence/rescue treatment by arm verified?", "needed": "Co-interventions/rescue treatment, adherence, changes/discontinuation and analytical handling by arm.", "role": "Required (effect of interest)", "role_reason": "Differences in rescue treatment may contribute to pain differences, so actual handling material is needed.", "application_exception": "Missing information does not mean that concomitant medication was absent.", "criterion": "Check actual analgesics, oral treatment, adherence, rescue treatment/discontinuation and analytical handling by arm.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link rescue-medication/co-intervention records to pain-assessment days and analysis populations to examine intervention contribution and the impact of treatment changes." }, { "item_id": "N11", "question_type": "Evidence condition", "question": "Are 84 completers and allocation/measurement/analysis denominators by arm verified?", "needed": "Allocation/measurement/completion/analysis flow and denominators by arm/assessment day.", "role": "Required (denominator attribution)", "role_reason": "Do not automatically substitute completers for randomized participants, ITT participants or denominators by arm.", "application_exception": "Do not split 84 equally between arms or calculate 0 missing participants.", "criterion": "Check the report of 84 completers against actual separate allocation, measurement and time-specific analysis denominators by arm.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link participant flow and denominators in each pain-result table without transferring the 84-completer count to another analysis population." }, { "item_id": "N12", "question_type": "Evidence condition", "question": "Are reasons for dropout/missingness and their handling in the pain analysis verified?", "needed": "Dropout/missingness reasons, timing, handling and sensitivity analyses by arm.", "role": "Required (missingness/selection)", "role_reason": "The information that 84 completed the trial does not establish absence of losses.", "application_exception": "Do not fill missing flow information with complete follow-up or 0 dropouts.", "criterion": "Check actual dropout, missingness by assessment day, reasons and pain-analysis/sensitivity handling by arm.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link participant flow to time-specific pain data to examine missingness-related selection and limitations in interpreting the effect of interest." }, { "item_id": "N13", "question_type": "Evidence condition", "question": "Are between-arm/within-arm contrasts, analytical models and effects of interest at each assessment verified?", "needed": "Contrast definitions, time-specific original results, models, ITT/PP and adjustment/repeated-measures handling.", "role": "Required (meaning of the estimate)", "role_reason": "Do not turn P values or directions from multiple assessment days into one integrated between-arm change.", "application_exception": "Do not invent ITT, change scores or time-integrated models when the original record does not identify the analysis.", "criterion": "Check actual arm order, final values/changes, between-arm/within-arm contrasts, repeated-measures models and analysis populations for each pain result.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare arm order, assessment time and analysis populations in pain-result tables with model descriptions to establish the actual estimated effect." }, { "item_id": "N14", "question_type": "Evidence condition", "question": "Are the reported lower pain scores and actual time-specific between-group values verified?", "needed": "Pain values by arm at each assessment, denominators, actual contrasts and P-test definitions.", "role": "Required (result attribution)", "role_reason": "Retain the favorable direction while preserving uncertainty about effect size.", "application_exception": "P<.05 alone does not establish a clinically large effect, cure or confirmed replication.", "criterion": "Retain the original lower-than-vehicle/P<.05 record and check actual assessment time, arm means/changes, denominators and contrast values.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Attribute each result to the same assessment time, scale, comparison and denominator to compare the original favorable direction with actual magnitude." }, { "item_id": "N15", "question_type": "Evidence condition", "question": "Are between-group pain differences, variance, denominators and 95% CI verified?", "needed": "Effect, variance type, denominators, 95% CI and analytical explanations for each actual contrast.", "role": "Required (precise effect)", "role_reason": "Neither 84 participants nor statistical significance substitutes for a precise effect.", "application_exception": "Do not invent a fixed minimum sample size or standard duration as a precision criterion.", "criterion": "Check pain differences, SD/SE, denominators and reported 95% CI for the selected actual contrast.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link original contrasts, variance, denominators and reported intervals to establish which effect the uncertainty concerns. Do not back-calculate in this work." }, { "item_id": "N16", "question_type": "Evidence condition", "question": "Are prespecified hierarchy and multiplicity handling across outcomes and assessment days verified?", "needed": "Outcome/time hierarchy, multiplicity and reasons for changes in the protocol, registration and SAP.", "role": "Required (selective-reporting review)", "role_reason": "Do not confuse the page’s selected pain question with the trial’s prespecified primary outcome.", "application_exception": "Do not inherit the original false coprimary-split flag as evidence that the prespecified hierarchy of the outcomes was verified.", "criterion": "Check the prespecified primary pain outcome, analytical hierarchy and multiplicity plans/handling among pain, size, erythema, exudation and assessment days.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link prespecified plans and original result tables to compare pain selection/assessment times, analytical changes and multiplicity handling." }, { "item_id": "N17", "question_type": "Evidence condition", "question": "Are a justified important difference for aphthous pain and the actual interval verified?", "needed": "Scale-specific important-difference basis, actual contrasts/CI and patient-relevant interpretation.", "role": "Required (interpretation of pain magnitude)", "role_reason": "Do not automatically equate statistical significance with a magnitude experienced by patients.", "application_exception": "Do not adopt arbitrary VAS points, fulfilment proportions or trial-count criteria.", "criterion": "Check a justified important-difference criterion for this population/pain scale against actual between-group estimates and intervals.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare the important-difference basis with actual between-group estimates/intervals for the same scale, population and period to examine the interpretable scope." }, { "item_id": "N18", "question_type": "Evidence condition", "question": "Are the actual identity and specifications of trial registration, protocol and SAP verified?", "needed": "Registration number, original registration/protocol/SAP, registration date and change history.", "role": "Required (plan comparison)", "role_reason": "Unverified registration number does not establish lack of a prespecified plan or confirmed selective reporting.", "application_exception": "No new search or external registration access is performed in this work.", "criterion": "Separately from the unverified registration record, check actual registration/protocol/SAP identity, dates and outcome/analysis specifications.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Once identity is acquired, compare original outcomes/results/times with prespecified specifications and changes. Do not equate currently unverified registration with nonregistration." }, { "item_id": "N19", "question_type": "Evidence condition", "question": "Are the family link for this report and other direct independent replication materials verified?", "needed": "Report/trial-family map, registration links and identity of replication material for the same question.", "role": "Required (replication/duplication boundary)", "role_reason": "Do not count a paper and its PubMed entry point as separate independent evidence.", "application_exception": "Do not turn absence of a search in this work or unverified replication in the original into 0 worldwide trials or an exact replication count.", "criterion": "Check the linked Jiang report/PMID/DOI and identity/independence of other comparisons with the same formulation, population and pain outcome.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare the relationships among PMID/DOI/registration, recruitment cohorts and assessment times to distinguish repeat citations from independent replication. Do not conduct a new exhaustive search or sum participants." }, { "item_id": "N20", "question_type": "Evidence condition", "question": "Are all assessment times and null or unfavorable results for the same pain question verified?", "needed": "Complete pain-result tables, assessment times/denominators, supplementary material and selection criteria.", "role": "Required (result selection)", "role_reason": "A favorable P-value summary does not establish the same direction for every result or absence of contrary results.", "application_exception": "Do not automatically classify numerical differences in other ulcer outcomes as conflicting pain data.", "criterion": "Check actual time-specific favorable, null and unfavorable pain results, contrasts, denominators and reporting scope.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare all pain results by assessment time, scale and contrast to examine favorable-result selection without treating different outcomes as conflicts." }, { "item_id": "N21", "question_type": "Evidence condition", "question": "Are government support, product provision, author employment and full COI material verified?", "needed": "Funding details, product provision, author employment/disclosures and design/analysis roles.", "role": "Required (comparison with original independence records)", "role_reason": "Government-support wording does not establish absence of product/COI issues or proven independence.", "application_exception": "Do not infer absence of bias from the original I1 label or funding name alone.", "criterion": "Check the Chinese non-US government-support record against actual product provision, author employment, roles and full COI disclosures.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link funding, product and author documents to design/analysis roles to examine actual disclosure levels and remaining uncertainty." }, { "item_id": "N22", "question_type": "Evidence condition", "question": "Are the short-term report on 84 people, actual safety denominators, event definitions and collection verified?", "needed": "All exposed/safety denominators, event/person counts by arm, collection methods and discontinuation reasons.", "role": "Supplementary; required for safety claims", "role_reason": "Do not extend an absence description from short-term completers to 0 events overall or to proven safety.", "application_exception": "Do not delete the retained pain observation because harm material is unverified or calculate a new incidence.", "criterion": "Check the short-term description of no obvious adverse effects against actual separate exposed/safety denominators, event definitions, collection and discontinuation reasons by arm.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link exposure by arm with safety tables/collection procedures to compare the scope of the completer-sample description with all actually exposed participants." }, { "item_id": "N23", "question_type": "Evidence condition", "question": "Are actual irritation, allergy and swallowed-exposure events, timing and alternative explanations verified?", "needed": "Irritation/allergy/swallowing events, exposure amount/timing, baseline/co-interventions and discontinuation/recovery.", "role": "Supplementary; required for the relevant harm", "role_reason": "Do not turn unverified safety issues into observed events or confirmed causality.", "application_exception": "Missing event material does not establish that irritation or allergy did not occur.", "criterion": "Check event definitions, exposure/onset, discontinuation/recovery, concurrent exposure and comparisons, distinguishing signal, frequency and causality.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link event records to actual local/swallowed exposure, timing and alternative explanations/comparators to examine the scope of what can be said." }, { "item_id": "N24", "question_type": "Evidence condition", "question": "Are pregnancy/lactation and safety/interaction materials beyond short follow-up verified?", "needed": "Direct exposure, events, duration and concomitant-use/interaction material by population.", "role": "Supplementary; required for expanded safety", "role_reason": "Do not extend 5-day general-adult material to pregnancy/lactation or overall long-term safety.", "application_exception": "Do not require every rare-harm study as a mandatory effect criterion for the original pain question.", "criterion": "Check direct exposure/event/comparison material on pregnancy, lactation, long-term/repeated application and concomitant medication.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare vulnerable-population/repeated-exposure material by formulation, route, population and follow-up, separating it from short-term general-adult material." }, { "item_id": "N25", "question_type": "Evidence condition", "question": "Were the pain effect and safety limitations retained as separate records?", "needed": "Links among pain observations, original safety text, denominators/duration and interpretation boundaries.", "role": "Required (description boundary)", "role_reason": "A favorable efficacy direction must not erase safety gaps.", "application_exception": "Meeting this record-separation criterion does not establish safety concerning irritation/allergy or pregnancy/lactation.", "criterion": "Link the original pain observation/P value and Caution/safety gaps separately; do not inherit efficacy reporting as safety verification.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "When subsequent efficacy/safety material arrives, compare outcome, denominator, period and actual reading scope separately and update the relevant links." }, { "item_id": "N26", "question_type": "Evidence condition", "question": "Does this checklist additionally require verification of optimal dosing or long-term persistence?", "needed": "For an extension claim: direct concentration/dose comparisons and long-term/withdrawal material.", "role": "Supplementary; required for the relevant extension", "role_reason": "Do not combine the narrow pain question with every dose-finding or persistence study.", "application_exception": "Actual nominal/application amount is covered in a separate row; unverified optimal amounts do not establish safe amounts.", "criterion": "Do not add optimal concentration/frequency, long-term persistence or withdrawal effects as mandatory confirmation beyond the selected 5 mg/g, 4-times-daily, 5-day scope.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If that extension is separately requested, examine designs comparing concentration/frequency and withdrawal/long-term results using the same pain definition." }, { "item_id": "N27", "question_type": "Evidence condition", "question": "Does the same effect question include size, erythema, exudation, healing, recurrence or infection treatment?", "needed": "For an extension: direct outcome definitions, comparisons, denominators, periods and results.", "role": "Supplementary; required for a separate outcome", "role_reason": "Do not extend a significant symptom score to cure or preventive effects.", "application_exception": "Retain other outcome observations, but do not invent values/effects absent from the retained source.", "criterion": "Separate the selected pain outcome from size/erythema/exudation, healing duration, recurrence and infection treatment; do not add those extensions as mandatory outcomes here.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "When separately examining an extension, design analyses separating its prespecified definition, direct results, denominators and period from pain." }, { "item_id": "N28", "question_type": "Evidence condition", "question": "Were the local summary, historical bibliography/abstract checks and currently unread external material distinguished?", "needed": "Material identity, links/original locations, actual reading scope, dates and original-document SHA.", "role": "Required (reading traceability)", "role_reason": "A PubMed link or an original bibliography/abstract-check statement does not establish full-text reading in this work.", "application_exception": "Do not assign inaccessible status to external material when access was not attempted.", "criterion": "Distinguish actual reading of the retained summary, the historical bibliography/abstract-check narrative, absent individual access records and external access not attempted/unread in this work.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Link actual access/reading events, locations, dates and SHA for subsequent material, keeping them separate from historical access." }, { "item_id": "N29", "question_type": "Evidence condition", "question": "Were the original types and records for C46, axes/flags and corrections retained?", "needed": "Original verdict, score/axes, flags, original decisions/corrections and whole-input SHA.", "role": "Required (original-text identity)", "role_reason": "Do not confuse the earlier clinical verdict with preparation of the current evidence checklist.", "application_exception": "Do not fill absent grade-revalidation, evidence-status or access fields with false values or new verification claims.", "criterion": "Link grade C, score 46, original axes/false flags, empty strings/arrays, grade decisions and corrections/dates to the exact input; do not inherit them as new condition scores.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If changes are requested, preserve the full previous text and case/version records to compare actual differences. This work does not reassess the verdict." }, { "item_id": "N30", "question_type": "Evidence condition", "question": "Were the original evidence date, current review date and scope of searches/checks distinguished?", "needed": "Original review date, case-review date, inputs used and actual search/calculation/access events.", "role": "Required (scope description)", "role_reason": "Do not turn the original evidence date into a date claiming completion of a current exhaustive literature search.", "application_exception": "Do not invent an original evidence-cutoff field or claim that it was the same field as the recorded review date.", "criterion": "Link the original review date with the case-review date, inputs used and the record of 0 new searches, calculations or external accesses in this work.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "When additional events occur, distinguish their performed scope/dates from historical records and link them to the relevant rows." }, { "item_id": "N31", "question_type": "Evidence condition", "question": "Were original search strategies, dates, screening/exclusions and unpublished/correction-check logs acquired?", "needed": "Historical search strategies/dates, search results, screening/exclusions and registration/unpublished/correction-check logs.", "role": "Required (scope of insufficiency/absence statements)", "role_reason": "Reading a retained abstract does not establish verification of all clinical literature.", "application_exception": "Unverified logs do not establish 0 human studies, 0 effect or 0 retractions.", "criterion": "Beyond the bibliography/abstract checks and oral/other-outcome exclusions, check actual search strategies/dates, results/screening and unpublished/registration/correction logs.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If historical logs are acquired, compare formulation/route/population/pain eligibility with search, screening and exclusion reasons. Do not conduct a new search in this work." }, { "item_id": "N32", "question_type": "Evidence condition", "question": "Were update criteria distinguishing new material from condition-version changes recorded?", "needed": "Actual subsequent originals, reading/dates, locations/values/SHA, full previous versions and condition versions/reasons for changes.", "role": "Required (record updates)", "role_reason": "Material additions or display changes must not automatically become clinical confirmation.", "application_exception": "Recording this update rule does not perform subsequent checks, reassessment or deployment.", "criterion": "Provide rules recording evidence additions with actual identity/reading/locations/values/SHA separately from revisions of the question or criteria.", "basis": "Existing method principles distinguish population, topical formulation, application, vehicle, pain scale, assessment days, denominators, allocation, missingness, plans, study families, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These topical berberine-gelatin and aphthous-ulcer pain conditions were developed with knowledge of the retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare actual subsequent material with question eligibility, outcome/time, denominators and comparator, then review the relevant rows. Freeze a separate version before applying condition revisions." } ] }