{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3070-s0", "verdict_number": "3070", "title": "Oral berberine alone or combined with letrozole × Cumulative live birth in infertility associated with PCOS", "view_version": "1.0", "view_created_date": "2026-10-27", "criteria_version": "1.0", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-08", "review_scope": { "materials_read": "Retained Korean/English summaries and case-specific condition/application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "Prepared from retained summaries and condition-application records. External abstracts, full texts, registration, protocols and analysis plans remain unread. Historical review records do not establish current independent clinical validation.", "date_meaning": "The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted." }, "claim_context": { "population": "The trial recruited 644 infertile women meeting Rotterdam PCOS criteria. The 644 describes the overall recruited population, not the analysis denominators of the selected two arms. Detailed diagnosis, age, infertility duration, other infertility causes, baseline prognosis and eligibility remain unverified.", "intervention": "The selected intervention is an oral berberine monotherapy strategy. Double-dummy tablets are described, but exact salt form, plant source, product, standardization and batch remain unverified. The combination arm provides context from the same trial and is not inherited as an observation of this monotherapy comparison.", "dose": "The planned berberine dose was 1.5 g/day. Comparator letrozole was planned at 2.5 mg on cycle days 3–7, increasing to 5 mg if needed. Actual administration, dose escalation, adherence, discontinuation and exposure after pregnancy remain unverified. This is not an instruction for personal use.", "comparator": "The comparator is an active letrozole monotherapy strategy. The overall study is described as a 3-arm double-blind, double-dummy randomized trial. Double-dummy placebos are not reinterpreted as a pure no-treatment control. The two derived comparisons share the letrozole arm.", "endpoint": "The endpoint is cumulative live birth during treatment. Retained reported rates are 36% with letrozole, 34% with the combination and 22% with berberine alone; the selected comparison is berberine 22% versus letrozole 36%. Event definition, arm-specific denominators/events and formal between-arm estimates/P/CI remain unverified. The original D grade, 34 points and Warning are retained as historical records, not a new assessment.", "duration": "Up to 6 months of treatment and pregnancy-outcome follow-up are described. Individual actual exposure, cycle counts, discontinuation and the length, end and completeness of follow-up through birth remain unverified. The maximum 6 months is not treated as every woman’s actual treatment duration or the end of birth follow-up.", "excluded_extensions": [ "Ovulation, pregnancy rates, insulin and weight outcomes do not replace a live-birth effect.", "Salt forms, plant extracts, combination products, dihydroberberine, other derivatives and topical products are not interchangeable.", "Do not generate arm denominators from 644/3 or back-calculate events from percentages. No new differences, RR, OR, NNT, CI or P are calculated.", "The same 3-arm trial and shared letrozole arm are not added as independent trials or independent participant populations.", "Retain the lower reported direction in the monotherapy arm without converting it into 0 effect, equivalence, noninferiority or formal between-arm precision.", "Retain the original pregnancy and fetal/neonatal bilirubin warning. Actual harm incidence, causation, post-pregnancy exposure and long-term safety remain unverified; no new personal dosing instruction is created.", "Distinguish ChiCTR-TRC-09000376 from the excluded NCT01116167 and retain the unverified entry in the original registration field.", "Reading retained summaries is not represented as current reading of external abstracts, full texts, registration, protocols or analysis plans." ] }, "requirements": [ { "item_id": "N01", "question_type": "Evidence condition", "question": "Is the question fixed to cumulative live birth with berberine alone versus letrozole alone?", "needed": "Linked records of the original claim, intervention, comparator and derived-comparison boundary", "role": "Required", "role_reason": "Separating a treatment-replacement question from an add-on question prevents monotherapy results from being read as combination effects.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Retain the original claim and explicitly identify berberine alone versus letrozole alone as a derived comparison.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If the boundary changes, redefine the actual intervention/comparator combination and review it in a separate version.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The original claim concerns cumulative live birth in infertile women with PCOS. This sheet concerns berberine alone versus letrozole alone; the original detailed-claim list is empty.", "condition_status": "Met", "status_reason": "The original claim and derived-comparison boundary match the current input and formal assignment. The derived ID was not turned into an index in the original detailed-claim list.", "missingness": "This is a boundary-record condition, separate from establishing a clinical effect.", "uncertainty": "This is a boundary-record condition, separate from establishing a clinical effect. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Linked records of the original claim, intervention, comparator and derived-comparison boundary" }, { "item_id": "N02", "question_type": "Evidence condition", "question": "Are the two monotherapy arms and the roles of double-dummy placebos distinguished in the retained account?", "needed": "Records of active ingredients, placebo allocation and actual comparator roles in the 3 arms", "role": "Required", "role_reason": "Changing the active letrozole comparator into a no-treatment comparator changes the meaning of the replacement strategy.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Select berberine alone and letrozole alone; do not read the double dummy as a pure no-treatment placebo arm.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If the full protocol is obtained, compare active/placebo allocation by arm and keep different strategies distinct.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The retained account describes double-dummy berberine/placebo and letrozole/placebo and a 3-arm RCT. The selected comparison is berberine alone versus letrozole alone.", "condition_status": "Met", "status_reason": "The selected arms’ roles can be distinguished in the current description. Actual success of blinding has not been established.", "missingness": "Detailed placebo implementation and successful blinding are separate gaps.", "uncertainty": "Detailed placebo implementation and successful blinding are separate gaps. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Records of active ingredients, placebo allocation and actual comparator roles in the 3 arms" }, { "item_id": "N03", "question_type": "Evidence condition", "question": "Are the trial berberine’s exact salt form, source, product and standardization established?", "needed": "Berberine product name, manufacturer, salt form, batch and standardization material", "role": "Required", "role_reason": "Product matching prevents monotherapy replacement results from being transferred to arbitrary berberine hydrochloride or plant products.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish the exact chemical form, product identifier, source, content standardization and application to the selected arm.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If original product material is obtained, compare composition and standardization and review unmatched products as separate questions.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The original claim conditions leave the exact salt form and plant source unverified. The retained account also keeps berberine hydrochloride, plant extracts, combination formulas and other derivatives distinct.", "condition_status": "Unverified", "status_reason": "The exact product form and standardization cannot be established from the retained material.", "missingness": "Product identifier, manufacturer, salt form and batch are absent.", "uncertainty": "Product identifier, manufacturer, salt form and batch are absent. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Berberine product name, manufacturer, salt form, batch and standardization material" }, { "item_id": "N04", "question_type": "Evidence condition", "question": "Are the planned oral berberine monotherapy dose, actual intake and adherence established?", "needed": "Arm-specific prescriptions, adherence, actual daily doses and discontinuation records", "role": "Required", "role_reason": "It is necessary to know whether actual exposure under the monotherapy strategy matched the planned dose.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Distinguish planned oral 1.5 g/day from actual intake, adherence, discontinuation and changes.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Use dosing records to distinguish planned from actual exposure and compare the effects of deviations with the predefined analysis.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The oral route and planned berberine 1.5 g/day are specified. Actual intake, adherence and discontinuation details are absent from current material.", "condition_status": "Partly verified", "status_reason": "The planned oral dose is established, while actual individual exposure is not.", "missingness": "Actual administration, adherence and the distribution of discontinuations remain unverified.", "uncertainty": "Actual administration, adherence and the distribution of discontinuations remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific prescriptions, adherence, actual daily doses and discontinuation records" }, { "item_id": "N05", "question_type": "Evidence condition", "question": "Are the active letrozole comparator’s planned dosing, escalation and actual administration established?", "needed": "Comparator-arm letrozole prescriptions by cycle, dose escalation and actual intake records", "role": "Required", "role_reason": "Unclear actual exposure to the active replacement comparator limits interpretation of the monotherapy-strategy comparison.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish planned comparator letrozole 2.5 mg on cycle days 3–7, increasing to 5 mg if needed, alongside actual escalation and administration.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare actual comparator dosing by cycle with the planned escalation criteria.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The plan of 2.5 mg on cycle days 3–7, increasing to 5 mg if needed, is retained. Actual escalation, cycle counts and adherence by arm are unverified.", "condition_status": "Partly verified", "status_reason": "The comparator drug’s plan is established, but actual administration records are unverified.", "missingness": "Actual arm-specific escalation and cycle counts are absent.", "uncertainty": "Actual arm-specific escalation and cycle counts are absent. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Comparator-arm letrozole prescriptions by cycle, dose escalation and actual intake records" }, { "item_id": "N06", "question_type": "Evidence condition", "question": "Are the actual population and Rotterdam PCOS/infertility eligibility criteria sufficiently established for the selected comparison?", "needed": "Diagnosis, age, infertility duration, inclusion/exclusion criteria and arm-specific population characteristics", "role": "Required", "role_reason": "Population conditions prevent extension of this monotherapy comparison to other infertility causes or women generally.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish the description of infertile women with Rotterdam PCOS and the detailed diagnostic, age and eligibility criteria.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If eligibility criteria and baseline tables are obtained, compare the target population with the actual trial population.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The recruited population is described as 644 infertile women meeting Rotterdam PCOS criteria. Detailed diagnosis, age, infertility duration and exclusions are absent from current material.", "condition_status": "Partly verified", "status_reason": "The principal population category is established, while detailed eligibility and arm-specific characteristics remain unverified.", "missingness": "The 644 describes the overall population, not the analysis denominator of either selected arm.", "uncertainty": "The 644 describes the overall population, not the analysis denominator of either selected arm. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Diagnosis, age, infertility duration, inclusion/exclusion criteria and arm-specific population characteristics" }, { "item_id": "N07", "question_type": "Evidence condition", "question": "Are baseline infertility causes, prior treatment and arm-specific prognostic characteristics established?", "needed": "Arm-specific baseline tables, investigations of infertility causes, prior treatment and medical histories", "role": "Required", "role_reason": "Actual data are needed to examine baseline prognostic balance when comparing the monotherapy replacement strategies.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish prognosis in the selected arms, including male/tubal factors, baseline ovulatory/metabolic status and previous treatment.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare baseline material with planned handling of prognostic variables and actual balance.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "Current material describes infertile women with Rotterdam PCOS but provides no tables of baseline causes, previous treatment or arm-specific characteristics.", "condition_status": "Unverified", "status_reason": "Material needed to establish baseline prognostic balance in the selected arms is absent.", "missingness": "Exclusion of other infertility causes and treatment histories remain unverified.", "uncertainty": "Exclusion of other infertility causes and treatment histories remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific baseline tables, investigations of infertility causes, prior treatment and medical histories" }, { "item_id": "N08", "question_type": "Evidence condition", "question": "Are actual random-sequence generation and implementation of the allocation ratio established in this multicenter trial?", "needed": "Random-sequence generation, stratification, site-specific allocation procedures and CONSORT flow material", "role": "Required", "role_reason": "More than the allocation description is needed to assess selection bias in the two monotherapy arms.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish not only the multicenter RCT and 1:1:1 description but also sequence generation, stratification and site-specific implementation.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare the protocol and allocation procedures to examine implementation of randomization for the selected arms.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "A multicenter double-blind 3-arm RCT with 644 participants and 1:1:1 allocation is described. Sequence generation, stratification and site-specific implementation remain unverified.", "condition_status": "Partly verified", "status_reason": "The design and allocation ratio are described, but actual randomization procedures are not established.", "missingness": "Detailed sequence generation, stratification and allocation by site are absent.", "uncertainty": "Detailed sequence generation, stratification and allocation by site are absent. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Random-sequence generation, stratification, site-specific allocation procedures and CONSORT flow material" }, { "item_id": "N09", "question_type": "Evidence condition", "question": "Are allocation concealment and recruitment procedures established for the two selected arms?", "needed": "Allocation concealment, enrollment timing, recruitment sequence and actual implementation material", "role": "Required", "role_reason": "Recruitment bias from predictable allocation also needs examination in an active-treatment replacement comparison.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish recruitment before allocation disclosure, concealment methods and actual implementation in the selected arms.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Obtain allocation/enrollment documents to examine concealment procedures in relation to recruitment timing.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The current summary describes an RCT but lacks details of allocation concealment, enrollment sequence and recruitment implementation.", "condition_status": "Unverified", "status_reason": "The label randomized trial cannot substitute for actual implementation of allocation concealment.", "missingness": "Allocation-concealment documents and recruitment records remain unverified.", "uncertainty": "Allocation-concealment documents and recruitment records remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Allocation concealment, enrollment timing, recruitment sequence and actual implementation material" }, { "item_id": "N10", "question_type": "Evidence condition", "question": "Are actual double-dummy blinding and the independence of live-birth ascertainment established?", "needed": "Placebo matching, maintenance/breaking of blinding, outcome assessors and verification procedures", "role": "Required", "role_reason": "These conditions examine dosing, subsequent treatment and ascertainment deviations in the comparison of two different active drugs.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish the double-blind/double-dummy description, placebo matching, unblinding or guessability and birth-ascertainment procedures.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare protocol and ascertainment documents to examine implementation of blinding and independence of outcome assessment.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "Multicenter double blinding and a double dummy are described. Placebo appearance, actual maintenance of blinding and the persons/procedures confirming births remain unverified.", "condition_status": "Partly verified", "status_reason": "The planned design is described, but actual blinding and ascertainment implementation are not established.", "missingness": "Maintenance of blinding and outcome-verification procedures are absent.", "uncertainty": "Maintenance of blinding and outcome-verification procedures are absent. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Placebo matching, maintenance/breaking of blinding, outcome assessors and verification procedures" }, { "item_id": "N11", "question_type": "Evidence condition", "question": "Are concomitant/rescue treatments and deviations established in the two monotherapy-strategy arms?", "needed": "Arm-specific concomitant/rescue treatment, crossover, other infertility treatment and reasons for discontinuation", "role": "Required", "role_reason": "Different subsequent treatments can prevent attribution solely to replacement with the monotherapy drug.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish actual concomitant/rescue and other infertility treatments and differences between the two monotherapy arms.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Reconstruct arm-specific treatment pathways to examine the definition of the effect of interest and appropriate handling of deviations.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The current summary gives only selected-arm names and planned doses; actual concomitant/rescue treatment, crossover and reasons for discontinuation are absent.", "condition_status": "Unverified", "status_reason": "Material needed to establish differences in other treatments within the selected comparison is absent.", "missingness": "Actual concomitant/rescue treatments and deviations remain unverified.", "uncertainty": "Actual concomitant/rescue treatments and deviations remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific concomitant/rescue treatment, crossover, other infertility treatment and reasons for discontinuation" }, { "item_id": "N12", "question_type": "Evidence condition", "question": "Are the maximum 6-month plan, actual individual treatment/cycle counts and exposure after pregnancy established?", "needed": "Arm-specific actual treatment duration, cycle counts, discontinuation timing and dosing after pregnancy", "role": "Required", "role_reason": "Treatment duration under the monotherapy strategy must not be changed into the total length of pregnancy follow-up.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Distinguish the maximum 6-month plan from actual treatment duration, ovulatory cycle counts, discontinuation and exposure after pregnancy confirmation.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Distinguish the treatment calendar from pregnancy follow-up and examine actual exposure duration and discontinuation pathways.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "A maximum 6 months and pregnancy-outcome follow-up are described as a plan. Actual individual administration, cycle counts, discontinuation and exposure after pregnancy remain unverified.", "condition_status": "Partly verified", "status_reason": "The duration plan is established, but actual exposure length and discontinuation pathways are not.", "missingness": "The maximum 6 months is not read as every woman’s actual exposure or the end of pregnancy follow-up.", "uncertainty": "The maximum 6 months is not read as every woman’s actual exposure or the end of pregnancy follow-up. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific actual treatment duration, cycle counts, discontinuation timing and dosing after pregnancy" }, { "item_id": "N13", "question_type": "Evidence condition", "question": "Are the length, end and completeness of pregnancy follow-up for live-birth ascertainment established?", "needed": "Arm-specific pregnancy/birth follow-up schedules, last contact, follow-up end and completeness", "role": "Required", "role_reason": "The observation window for birth outcomes in the monotherapy comparison can differ from treatment duration.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Distinguish treatment end from follow-up after pregnancy through birth and establish arm-specific follow-up start, end and completeness.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare the observation window from pregnancy onset to birth confirmation with incomplete follow-up.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The original claim conditions state a maximum 6 months with pregnancy-outcome follow-up, but length through birth, arm-specific follow-up end and completeness are absent.", "condition_status": "Unverified", "status_reason": "The exact observation window used to establish birth outcomes cannot be determined from current material.", "missingness": "Pregnancy follow-up length and completeness remain unverified.", "uncertainty": "Pregnancy follow-up length and completeness remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific pregnancy/birth follow-up schedules, last contact, follow-up end and completeness" }, { "item_id": "N14", "question_type": "Evidence condition", "question": "Are the event definition, cumulative method and measurement unit of cumulative live birth sufficiently established?", "needed": "Endpoint definition, birth-verification procedures, cycle-accumulation rules and handling of multiple/repeated births", "role": "Required", "role_reason": "Ovulation, pregnancy or infant counts must not be substituted for cumulative live birth per woman in the monotherapy comparison.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish the cumulative-live-birth label, gestational-age criteria, woman/infant unit, accumulation across cycles, multiple-birth handling and verification procedures.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Obtain endpoint specifications to examine consistency of woman, cycle and infant units with cumulative counting.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "Cumulative live birth during treatment is specified as the principal endpoint. Gestational-age criteria, woman/infant units, multiple births and cumulative counting rules remain unverified.", "condition_status": "Partly verified", "status_reason": "The principal endpoint label is established, but actual event definition and unit are not sufficiently established.", "missingness": "Event definition, unit and verification procedures remain unverified.", "uncertainty": "Event definition, unit and verification procedures remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Endpoint definition, birth-verification procedures, cycle-accumulation rules and handling of multiple/repeated births" }, { "item_id": "N15", "question_type": "Evidence condition", "question": "Are the original reported rates of 22% versus 36% accurately attributed to the monotherapy comparison?", "needed": "Attribution records linking each arm’s reported rate, name, original statement and result location", "role": "Required", "role_reason": "This condition preserves observations for the monotherapy comparison without confusing reported rates across the three arms.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Link berberine 22% and letrozole 36% to the selected comparison and retain combination 34% as original context.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "When new reports are obtained, first verify arm names for the same endpoint, denominator and time, then compare with existing attribution.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The original results are letrozole 36%, combination 34% and berberine 22%. The selected monotherapy comparison is berberine 22% versus letrozole 36%; no new difference or statistic was calculated.", "condition_status": "Met", "status_reason": "The narrow attribution of arm names and reported rates matches the retained account. This does not establish formal between-arm effects or precision.", "missingness": "Arm-specific events, denominators and formal effect estimates remain separately unverified.", "uncertainty": "Arm-specific events, denominators and formal effect estimates remain separately unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Attribution records linking each arm’s reported rate, name, original statement and result location" }, { "item_id": "N16", "question_type": "Evidence condition", "question": "Are randomized, analyzed, completed and endpoint-observed denominators established for the two selected arms?", "needed": "CONSORT counts, analysis populations, birth-endpoint denominators and missing-data flow for the two selected arms", "role": "Required", "role_reason": "Denominators for the two monotherapy arms must not be replaced by the overall 644 or by 644/3.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Distinguish the overall 644-participant allocation description from each selected arm’s randomized, analyzed, completed and endpoint-observed numbers.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare definitions of each denominator to distinguish overall allocation from the endpoint-analysis population.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "Only 644 participants overall and 1:1:1 allocation are described. Arm-specific randomized, analyzed, completed and birth-observed denominators are absent.", "condition_status": "Unverified", "status_reason": "The overall count and allocation ratio do not establish actual integer denominators for each arm.", "missingness": "Do not use a 644/3 calculation or denominators from the other sheet.", "uncertainty": "Do not use a 644/3 calculation or denominators from the other sheet. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "CONSORT counts, analysis populations, birth-endpoint denominators and missing-data flow for the two selected arms" }, { "item_id": "N17", "question_type": "Evidence condition", "question": "Are live-birth event counts and person/infant/cycle units established for the two selected arms?", "needed": "Original live-birth events, denominators, units and handling of repeated/multiple births", "role": "Required", "role_reason": "Reported percentages alone cannot generate birth events or women for the monotherapy arms.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish original event counts and the person/infant/cycle units of their denominators without back-calculating reported rates.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Obtain original result tables to examine the relation between events and person/cycle denominators.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The original results contain only three-arm percentages; original live-birth events, denominators and repeated/multiple-birth handling are absent.", "condition_status": "Unverified", "status_reason": "Percentages alone cannot establish actual event counts or units.", "missingness": "No new back-calculation, rounded event counts or application of a 644 denominator is performed.", "uncertainty": "No new back-calculation, rounded event counts or application of a 644 denominator is performed. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original live-birth events, denominators, units and handling of repeated/multiple births" }, { "item_id": "N18", "question_type": "Evidence condition", "question": "Are the effect of interest, ITT/PP and handling of intercurrent events established for the monotherapy-strategy comparison?", "needed": "Estimand specifications, ITT/PP populations and plans/results for intercurrent events and missing data", "role": "Required", "role_reason": "Replacement-strategy effects and effects of actual monotherapy intake can differ.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Define whether the effect concerns assigned monotherapy strategies or actual intake and establish handling of pregnancy, discontinuation, rescue treatment, missing data and ITT/PP.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "After establishing the estimand and analysis populations, examine how pregnancy, discontinuation and rescue treatment enter the definition.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The current summary gives only the principal endpoint and arm-level reported rates; estimand, ITT/PP and specifications for intercurrent events or missing data are absent.", "condition_status": "Unverified", "status_reason": "The effect of interest and actual analysis population for the selected comparison have not been established.", "missingness": "The distinction between monotherapy/add-on strategy effects and actual-intake effects remains unverified.", "uncertainty": "The distinction between monotherapy/add-on strategy effects and actual-intake effects remains unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Estimand specifications, ITT/PP populations and plans/results for intercurrent events and missing data" }, { "item_id": "N19", "question_type": "Evidence condition", "question": "Are the formal estimator, method, P and confidence interval for the selected between-arm effect established?", "needed": "Original between-arm effect estimates, model, P, confidence interval, denominator and endpoint time", "role": "Required", "role_reason": "Reported monotherapy rates must be distinguished from formal replacement-effect precision.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish original estimates, uncertainty, denominator and time from an appropriate unadjusted or adjusted between-arm model.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare original analysis tables and the SAP to establish comparison estimates and precision. Do not exclude an unadjusted analysis solely because it is unadjusted.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "Current material contains only arm-specific percentages; the formal effect estimator, model, P and confidence interval for the selected comparison are absent.", "condition_status": "Unverified", "status_reason": "Reported rates are established, but material needed to establish formal comparison estimates and confidence intervals is absent.", "missingness": "No new difference, RR, OR, NNT, CI or P is calculated.", "uncertainty": "No new difference, RR, OR, NNT, CI or P is calculated. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original between-arm effect estimates, model, P, confidence interval, denominator and endpoint time" }, { "item_id": "N20", "question_type": "Evidence condition", "question": "Are clinical importance and interpretation criteria for superiority, noninferiority or equivalence established for the selected comparison?", "needed": "Hypotheses, clinical-importance/noninferiority margins, effect confidence intervals and interpretation plans", "role": "Required", "role_reason": "The unfavorable monotherapy direction and the magnitude/precision of clinically important differences require separate examination.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Compare prespecified hypotheses and clinical-importance criteria with the corresponding confidence interval; do not convert nonsignificance or original no-benefit wording into equivalence.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Establish original hypotheses and margins, then examine how confidence intervals address clinically important differences.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The retained account describes a lower live-birth direction with monotherapy. Importance criteria, superiority/noninferiority/equivalence hypotheses and confidence intervals remain unverified.", "condition_status": "Unverified", "status_reason": "The original conclusion’s direction alone cannot newly establish clinical importance, equivalence or 0 effect.", "missingness": "Prespecified margins, confidence intervals and clinical-importance criteria are absent.", "uncertainty": "Prespecified margins, confidence intervals and clinical-importance criteria are absent. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Hypotheses, clinical-importance/noninferiority margins, effect confidence intervals and interpretation plans" }, { "item_id": "N21", "question_type": "Evidence condition", "question": "Are losses, missing data, incomplete birth follow-up and the effects of their handling established for the selected arms?", "needed": "Arm-specific losses, missing/incomplete pregnancy or birth follow-up, reasons, handling and sensitivity material", "role": "Required", "role_reason": "Reported monotherapy-strategy rates can depend on handling of women not followed up.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish arm-specific missing data, reasons for loss, unconfirmed births, analysis handling and sensitivity analyses.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Examine consistency between missing-data flow and planned handling and establish the scope of original sensitivity analyses.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The current summary lacks counts of losses, missing data and incomplete birth follow-up, their handling and sensitivity results.", "condition_status": "Unverified", "status_reason": "Material needed to establish how missing-data handling affects reported arm-level rates is absent.", "missingness": "Missing data are not treated as 0 events or complete follow-up.", "uncertainty": "Missing data are not treated as 0 events or complete follow-up. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific losses, missing/incomplete pregnancy or birth follow-up, reasons, handling and sensitivity material" }, { "item_id": "N22", "question_type": "Evidence condition", "question": "Is consistency of preregistration, protocol and SAP with actual reporting established for the selected comparison?", "needed": "Actual ChiCTR/WHO registration versions, change histories, protocol, SAP and original result tables", "role": "Required", "role_reason": "More than a registration number is needed to establish that this monotherapy comparison and analysis were prespecified.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Use the ChiCTR identifier as a lead to compare actual registration versions, timing, selected arms, endpoints and analysis plans with the original report.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If registration and SAP are obtained, compare registration timing, hypotheses, arms, endpoints and analyses with reporting.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "ChiCTR-TRC-09000376 and a historical statement matching the paper with WHO/ChiCTR are retained. Actual registration versions, SAP and change history have not currently been acquired or read.", "condition_status": "Unverified", "status_reason": "The identifier and historical matching statement alone do not establish consistency between actual prior plans and reporting.", "missingness": "Registration timing, protocol, SAP and change history remain unverified.", "uncertainty": "Registration timing, protocol, SAP and change history remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Actual ChiCTR/WHO registration versions, change histories, protocol, SAP and original result tables" }, { "item_id": "N23", "question_type": "Evidence condition", "question": "Are multiplicity handling and hypothesis hierarchy established for the two derived comparisons in the 3-arm trial?", "needed": "3-arm hypothesis hierarchy, multiplicity handling, comparison-specific SAP and reported results", "role": "Required", "role_reason": "Splitting a 3-arm trial into two sheets still requires establishing the monotherapy comparison’s hypothesis hierarchy.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish prespecified hierarchy and multiplicity handling for the monotherapy/add-on comparisons and examine reporting selection.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare the original SAP with complete results to examine comparison selection and multiplicity handling.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The original material describes a 3-arm RCT but lacks the two comparisons’ prespecified hierarchy, multiplicity handling and selection from all results.", "condition_status": "Unverified", "status_reason": "Producing two sheets does not establish the trial’s hypotheses or handling of multiplicity.", "missingness": "Comparison hierarchy and multiplicity handling remain unverified.", "uncertainty": "Comparison hierarchy and multiplicity handling remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "3-arm hypothesis hierarchy, multiplicity handling, comparison-specific SAP and reported results" }, { "item_id": "N24", "question_type": "Evidence condition", "question": "Are both the unfavorable monotherapy direction and the historical no-added-benefit statement retained?", "needed": "Preservation records of original results, counterviews, original assessment, axes and correction history", "role": "Required", "role_reason": "The unfavorable monotherapy observation must not be covered over by metabolic possibilities or add-on results.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Retain all three-arm rates, original conclusions, D 34 and all axes without alteration rather than selecting favorable results only.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If subsequent reports become available, compare favorable, unfavorable and no-benefit material under the same attribution rules and record changes as separate events.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The original three-arm rates, statements that monotherapy was lower and addition did not increase live birth, the separate metabolic counterview, D 34 and all axes are retained.", "condition_status": "Met", "status_reason": "The current input’s unfavorable direction, counterview and assessment were not deleted or recalculated. This is not new certification of clinical effects.", "missingness": "Formal comparison statistics and precision remain unverified.", "uncertainty": "Formal comparison statistics and precision remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Preservation records of original results, counterviews, original assessment, axes and correction history" }, { "item_id": "N25", "question_type": "Evidence condition", "question": "Are the ChiCTR link, exclusion of the wrong NCT and original unverified registration-field wording kept distinct?", "needed": "Linked records of PMID, DOI, ChiCTR, excluded NCT and the original registration field", "role": "Required", "role_reason": "These records prevent the monotherapy trial’s identity from being changed to an incorrect unrelated registration.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Distinguish ChiCTR-TRC-09000376/PMID/DOI from the excluded NCT01116167 and retain the original registration field’s “not established” wording.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If actual registration material is obtained, compare identifiers, population, 3 arms and endpoints and record discrepancies as separate correction events.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The bibliography lists PMID 27336209, DOI 10.1016/j.fertnstert.2016.05.022 and ChiCTR-TRC-09000376. The original central point excludes NCT01116167, while the evidence-table registration field remains “not established.”", "condition_status": "Met", "status_reason": "The established historical identifier link and the original field’s unverified label are retained separately. Current external registration verification is not complete.", "missingness": "Current comparison with original registration material was not attempted.", "uncertainty": "Current comparison with original registration material was not attempted. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Linked records of PMID, DOI, ChiCTR, excluded NCT and the original registration field" }, { "item_id": "N26", "question_type": "Evidence condition", "question": "Is it explicit that the two derived sheets concern the same 3-arm trial and shared letrozole arm?", "needed": "Relationship records linking one study family, two comparisons, the shared control and report identifiers", "role": "Required", "role_reason": "Displaying monotherapy and add-on comparisons as separate questions must not double-count one study’s control arm.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Group the same PMID/DOI/ChiCTR into one study family and do not add the two sheets/shared control as independent trials or independent participants.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare report populations, recruitment and identifiers to link the same family and duplicated controls.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The retained original set contains 1 3-arm RCT report. Both sheets share the same 644-participant trial and letrozole control and are not counted as independent repeated trials or two participant populations.", "condition_status": "Met", "status_reason": "The two comparisons and shared-control relationship within the same report are explicit.", "missingness": "Exact comparison-specific analysis denominators and covariance remain separately unverified.", "uncertainty": "Exact comparison-specific analysis denominators and covariance remain separately unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Relationship records linking one study family, two comparisons, the shared control and report identifiers" }, { "item_id": "N27", "question_type": "Evidence condition", "question": "Are independent replication of the same question and the scope of access established?", "needed": "Identities, reports, search scope and original material for independently recruited studies", "role": "Required", "role_reason": "Splitting the same 3-arm report into two sheets does not establish replication of the monotherapy replacement comparison.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Establish separately recruited studies of the same population, exposure, comparator and live-birth endpoint and the actual reading/search scope.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If new-material review is authorized, assess question-specific eligibility and compare independent recruitment and report overlap.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The current retained set contains 1 direct 3-arm trial report, and no new clinical search was performed. Material establishing independent replication is absent.", "condition_status": "Unverified", "status_reason": "Having one retained report does not prove that only one human study, or no human studies, exist worldwide.", "missingness": "Independent replication of the same question and comprehensive search scope remain unverified.", "uncertainty": "Independent replication of the same question and comprehensive search scope remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Identities, reports, search scope and original material for independently recruited studies" }, { "item_id": "N28", "question_type": "Evidence condition", "question": "Is there an applicable set for examining heterogeneity between distinct independent trials in the current retained material?", "needed": "Differences in populations, interventions, endpoints and analyses if additional independent families are established", "role": "Supplementary; required when synthesizing multiple independent study families", "role_reason": "The one family retained for the monotherapy comparison is not synthesized as multiple independent trials.", "application_exception": "With only one family in the current retained set, between-trial heterogeneity is not applicable. Differences between comparisons within the study and dependence from the shared control remain subject to examination.", "criterion": "Do not treat two comparisons in the same study family as between-trial heterogeneity; examine differences between trials when another eligible family is established.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If a separate family is obtained, compare question matching and design, population and estimator differences to examine whether synthesis is appropriate.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The current retained report set contains only 1 direct 3-arm trial, and the two derived sheets belong to the same family. Multiple families needed for between-independent-trial heterogeneity are absent from this set.", "condition_status": "Not applicable", "status_reason": "There is no narrow applicable set for between-independent-trial heterogeneity in the current retained material. Unverified replication, denominators or precision are not changed to not applicable.", "missingness": "Whether other studies exist remains separately unverified.", "uncertainty": "Whether other studies exist remains separately unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Differences in populations, interventions, endpoints and analyses if additional independent families are established" }, { "item_id": "N29", "question_type": "Evidence condition", "question": "Are monotherapy dose response, longer-term effects and subgroup effects beyond the trial dose/duration established?", "needed": "Direct comparisons and interaction data for additional doses, durations, products and subgroups", "role": "Supplementary; required when extending to other doses, durations or subgroups", "role_reason": "The berberine 1.5 g/day monotherapy trial is not extended to replacement effects for all doses, forms and long-term exposures.", "application_exception": "The narrow selected comparison does not always require evidence for every dose. Direct evidence is needed only for the extension being considered.", "criterion": "Establish extensions beyond actual trial dose, duration and population using direct material and prespecified subgroup/interaction evidence.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "When an extension question is needed, review its material as a separate question; do not read simple subgroup differences as interactions.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "Current material describes berberine 1.5 g/day, a maximum 6-month plan and results in specific infertile women with PCOS. Direct material for other doses, longer durations and subgroups is absent.", "condition_status": "Unverified", "status_reason": "Current material does not establish extended effects. This gap differs from the formal effect of the narrow selected comparison.", "missingness": "Extensions beyond the trial dose, duration and population remain unverified.", "uncertainty": "Extensions beyond the trial dose, duration and population remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Direct comparisons and interaction data for additional doses, durations, products and subgroups" }, { "item_id": "N30", "question_type": "Evidence condition", "question": "Is the boundary between live birth and ovulation, pregnancy, metabolic or weight outcomes maintained?", "needed": "Records of endpoint hierarchy and attribution boundaries for other outcomes", "role": "Required", "role_reason": "Birth results in the monotherapy arm must not be replaced by other intermediate outcomes.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Fix the selected comparison to cumulative live birth; do not replace it with possible effects on ovulation, pregnancy rates, insulin or weight.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If material on other outcomes is obtained, review those questions separately and interpret their relationship to live birth only where direct linking evidence exists.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The original explanation and summary state that only live birth is assessed and that ovulation, pregnancy rates, insulin and weight are separate. This sheet maintains that boundary.", "condition_status": "Met", "status_reason": "The narrow record condition of keeping the principal birth endpoint distinct from other intermediate outcomes is established.", "missingness": "Actual effects on other outcomes are not newly assessed in this sheet.", "uncertainty": "Actual effects on other outcomes are not newly assessed in this sheet. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Records of endpoint hierarchy and attribution boundaries for other outcomes" }, { "item_id": "N31", "question_type": "Evidence condition", "question": "Are funding, product support, author relationships and conflicts specifically established?", "needed": "Funding bodies, research funding, berberine/letrozole supply, author relationships and conflict declarations", "role": "Required", "role_reason": "Funding/product influence on monotherapy replacement results must be examined through actual arm-specific support details.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Distinguish the public-research-network description from actual supporting institutions, product supply, author relationships and conflict declarations.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare original support and conflict statements to establish research funding, product provision and author relationships separately.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The original funding field says “public research network; details of product support to be checked.” Exact institutions, product providers, author relationships and conflict details are absent from current material.", "condition_status": "Partly verified", "status_reason": "The support category is described, while product-support and conflict details are not established. Generic English wording does not replace actual declaration content.", "missingness": "Detailed supporting institutions, providers, author relationships and declarations remain unverified.", "uncertainty": "Detailed supporting institutions, providers, author relationships and declarations remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Funding bodies, research funding, berberine/letrozole supply, author relationships and conflict declarations" }, { "item_id": "N32", "question_type": "Evidence condition", "question": "Are actual maternal, pregnancy and fetal/neonatal harm collection and results established for the selected comparison?", "needed": "Arm-specific maternal/pregnancy/fetal/neonatal harm definitions, active collection, event/person denominators, timing, exposure, discontinuation and concomitant-treatment material", "role": "Supplementary; required when explaining pregnancy safety or personal-use decisions", "role_reason": "The monotherapy live-birth comparison alone cannot establish pregnancy safety, so separate harm information is needed.", "application_exception": "The principal question concerns live-birth efficacy. Harm incidence is not imposed as an efficacy condition, while safety explanation and personal application require separate direct material.", "criterion": "Establish arm-specific harm definitions, collection methods, exposure/follow-up timing, event/person denominators, discontinuations, concomitant treatment and actual results.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If original safety material is obtained, compare harm definitions, collection, follow-up, denominators and discontinuation/concomitant treatment to distinguish signals from comparative risks.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The retained account contains warnings about trying to conceive and fetal/neonatal bilirubin. Actual harm events, person denominators, timing, collection, discontinuation and comparative risks for the selected arms are absent.", "condition_status": "Unverified", "status_reason": "Warning statements do not replace confirmation of actual trial harm collection and incidence.", "missingness": "Actual harms, incidence, exposure after pregnancy and long-term safety remain unverified; no new calculation is performed.", "uncertainty": "Actual harms, incidence, exposure after pregnancy and long-term safety remain unverified; no new calculation is performed. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific maternal/pregnancy/fetal/neonatal harm definitions, active collection, event/person denominators, timing, exposure, discontinuation and concomitant-treatment material" }, { "item_id": "N33", "question_type": "Evidence condition", "question": "Are historical warnings, actual trial harms and personal-use decisions kept distinct?", "needed": "Records distinguishing the roles of original safety warnings and actual event material", "role": "Required", "role_reason": "The monotherapy strategy’s live-birth result and the original pregnancy warning have different roles in the evidence.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Retain original warnings without promoting them to actual risk estimates, established causation, long-term safety or new personal dosing instructions.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If original safety material is added, establish the warning’s basis, population and events and examine these separately from comparative risk.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The original safety warning and advice to consult a clinician are retained as historical text. This sheet does not turn them into new incidence estimates, established causation, safety at every dose or personal dosing instructions.", "condition_status": "Met", "status_reason": "The narrow record condition distinguishing historical warnings from this sheet’s material-verification scope is established.", "missingness": "Actual risk estimates and personal-application decisions remain unverified.", "uncertainty": "Actual risk estimates and personal-application decisions remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Records distinguishing the roles of original safety warnings and actual event material" }, { "item_id": "N34", "question_type": "Evidence condition", "question": "Are the original review date, correction date, current sheet-review date and search/reading limits distinguished?", "needed": "Original review date, correction date, current review date, search scope and actual access records", "role": "Required", "role_reason": "Currency of the monotherapy comparison cannot be established by changing the original review date into a new search date.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Retain original review and correction dates, do not infer absent cutoff/individual access dates, and distinguish whether current new searches or external reading occurred.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "When new evidence updating is authorized, record search dates, scope and access events as new records without backdating historical dates.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The original verdict review date is 2026-09-08 and the correction date is 2026-09-14. This sheet’s record-review date is 2026-10-05; no new clinical search or external reading was performed. Original search-cutoff and report-specific access-date fields are absent.", "condition_status": "Met", "status_reason": "Different dates and the actual current reading scope are recorded separately. This does not establish a completed comprehensive current search.", "missingness": "Individual external access dates and search cutoff are not inferred where original fields are absent.", "uncertainty": "Individual external access dates and search cutoff are not inferred where original fields are absent. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original review date, correction date, current review date, search scope and actual access records" }, { "item_id": "N35", "question_type": "Evidence condition", "question": "Are English correction history, remaining generic wording and original null/empty values retained?", "needed": "Preservation records of original corrections, bilingual fields, empty values, absent fields and types", "role": "Required", "role_reason": "Generic English wording must not be read as new denominator, confidence-interval or funding facts for the monotherapy comparison.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Do not fill the 1 correction or remaining generic verification wording with specific clinical values; retain empty detailed-claim lists/review notes, original axes and original types.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If a new bilingual correction is needed, establish corresponding original values and the correction event and preserve the entire text before change.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The record describes a 2026-09-14 correction of 1 generic English field while retaining grade, score and date. Remaining generic sample-size, funding and result English wording, empty detailed-claim lists/review notes and the complete original material are retained.", "condition_status": "Met", "status_reason": "Specific translations remain distinguished from generic verification wording, without generating absent numbers, confidence intervals or funding declarations.", "missingness": "Remaining generic wording does not establish the corresponding actual clinical values.", "uncertainty": "Remaining generic wording does not establish the corresponding actual clinical values. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Preservation records of original corrections, bilingual fields, empty values, absent fields and types" }, { "item_id": "N36", "question_type": "Evidence condition", "question": "Are current retained-summary reading, unread external materials and historical matching statements separated by material type?", "needed": "Material-specific current acquisition/reading, URL, version, historical access date/level and original-location records", "role": "Required", "role_reason": "Reading a monotherapy-comparison summary must not be represented as rereading the paper’s full text.", "application_exception": "This condition concerns actual material for the selected comparison. Information from another known comparison, a non-live-birth endpoint or a different product does not substitute for it; no arbitrary sample-size threshold is imposed.", "criterion": "Distinguish actual reading of retained summaries from current unattempted/unread PubMed, DOI, paper, registration and SAP materials; do not inherit access levels/dates from a containing document.", "basis": "Existing method principles distinguish population, active treatment, actual exposure, cumulative live birth, follow-up, denominators, analysis, shared controls, funding and harms. Detailed conditions are Chamgap’s own application.", "condition_origin": "These conditions concern cumulative live birth with berberine alone versus letrozole alone and were developed with knowledge of the retained content. They were frozen before application; this does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If external material is actually obtained, verify its own access event, version and original locations and update only the current reading record.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.", "observation": "The complete bilingual account, evidence, bibliography and corrections in the current input were read. The original research-review statement about matching the paper with WHO/ChiCTR is historical; all current external access and reading remain unattempted. Individual access dates/levels are null because the original fields are absent.", "condition_status": "Met", "status_reason": "Actual current local reading, unread external materials and historical statements are separated by physical material type.", "missingness": "Individual external access levels/dates and current full-text versions remain unverified.", "uncertainty": "Individual external access levels/dates and current full-text versions remain unverified. No new difference/CI/denominator/incidence/grade calculation or reassessment.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Material-specific current acquisition/reading, URL, version, historical access date/level and original-location records" } ], "reports": [ { "report_id": "S01", "title": "Wu 2016 PCOS double-dummy 3-arm cumulative live-birth report", "url": "https://pubmed.ncbi.nlm.nih.gov/27336209/", "report_type": "Retained bibliographic and result summary of the same 3-arm randomized trial. The selected question is monotherapy versus active letrozole.", "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "study_family": "The same Wu 2016/ChiCTR-TRC-09000376 study family with a shared letrozole control", "observed_result": "Described as a multicenter double-blind 3-arm trial with 644 participants overall and 1:1:1 allocation. Reported cumulative live-birth rates are 36% with letrozole, 34% with the combination and 22% with berberine. This sheet concerns monotherapy: berberine 22% versus letrozole 36%. The lower monotherapy direction is retained, while arm-specific n/events, formal effects/P/CI, pregnancy follow-up length, product support and actual harms remain unverified. The original planned berberine 1.5 g/day, letrozole 2.5 mg on cycle days 3–7 increasing to 5 mg if needed, and maximum 6 months are not converted into actual individual exposure or the end of birth follow-up.", "result_level": "Arm-level reported rates and the historical direction of conclusions in the retained summary. The paper, registration and analysis plan are currently unread; no separate effect calculation or reassessment was performed.", "source_evidence_date": "2026-09-08", "materials": [ { "material_type": "Retained Korean/English bibliographic and research summary", "public_status": "Retained copy acquired; summary read", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Stored existing review summary read", "as_of": "2026-10-05", "qualification": "The currently retained summary was read. It is distinguished from the paper’s full text. Retained bilingual bibliographic and result summaries were read. Historical statements about matching the paper with WHO/ChiCTR are not inherited as current full-text or registration reading. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted." }, { "material_type": "PubMed bibliographic/abstract entry", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Only a bibliographic entry is linked; current availability, abstract version and text were not checked. Retained bilingual bibliographic and result summaries were read. Historical statements about matching the paper with WHO/ChiCTR are not inherited as current full-text or registration reading. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted." }, { "material_type": "DOI/publisher entry", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "This DOI entry comes from retained bibliography. The current publisher page, full-text availability and version were not checked. Retained bilingual bibliographic and result summaries were read. Historical statements about matching the paper with WHO/ChiCTR are not inherited as current full-text or registration reading. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted." }, { "material_type": "Original paper full text", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The physical full text’s direct URL, version and retained original remain unverified. A bibliographic link does not mean the full text was read. Retained bilingual bibliographic and result summaries were read. Historical statements about matching the paper with WHO/ChiCTR are not inherited as current full-text or registration reading. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted." }, { "material_type": "Original WHO/ChiCTR registration material", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Only the identifier and historical matching statement are retained. The actual registration version, timing and change history remain currently unverified. Retained bilingual bibliographic and result summaries were read. Historical statements about matching the paper with WHO/ChiCTR are not inherited as current full-text or registration reading. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted." }, { "material_type": "Original protocol, analysis plan and supplementary material", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Identity, existence, direct URLs and versions of the protocol, analysis plan and supplementary material remain unverified. Retained bilingual bibliographic and result summaries were read. Historical statements about matching the paper with WHO/ChiCTR are not inherited as current full-text or registration reading. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/27336209/" } ], "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted." } ], "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": "The condition has no applicable subject within the current retained set and narrow question. This does not replace a material gap or unread status.", "Not reported": "Limited to the particular material or section actually read. It is not extended to the entirety of an unread external paper.", "Review incomplete": "A status for external original-material comparison not yet performed, distinguished from review of locally retained content." }, "study_overlap": { "state": "Unverified", "unique_trial_count": null, "unique_participant_count": null, "reason": "The retained set contains 1 3-arm report linked to PMID 27336209, DOI 10.1016/j.fertnstert.2016.05.022 and ChiCTR-TRC-09000376. The two derived comparisons share the same study family and letrozole arm. Comparison-specific analysis denominators, covariance and unique participant totals remain unverified. This does not establish independent replication or a new sum of participants." }, "history": [ { "date": "2026-10-27", "kind": "Separation of public-facing pages and materials", "view_version": "1.0", "change": "The public view and materials were prepared from the existing 36 items. No new clinical search, verification-state change or scoring was performed." } ], "language": "en", "translation_date": "2026-10-27" }