{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v2938-s0", "verdict_number": "2938", "title": "Everolimus · advanced hepatocellular carcinoma after sorafenib · evidence check for improved overall survival", "view_version": "1.0", "view_created_date": "2026-10-11", "criteria_version": "1.0", "criteria_date": "2026-10-06", "review_date": null, "legacy_evidence_date": "2026-08-26", "review_scope": { "materials_read": "Existing review summaries and stored records of methodological application", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "Original results and gaps were documented from the specified preserved summary. External abstracts, full texts and registration remain unread and access was not attempted. Historical production records state that additional content review, testing, link or screen checks were not performed then. Existing content review remains incomplete.", "date_meaning": "This is the date the stored materials were checked, not the date of a new search of the clinical literature." }, "claim_context": { "population": "Child-Pugh A advanced hepatocellular carcinoma after sorafenib failure or intolerance; original selected population at 121 centers in 17 countries", "intervention": "Original trial intervention of everolimus plus best supportive care", "dose": "Historical research exposure of 7.5 mg/day; nominal or actual exposure, formulation and route details remain unverified; not dosing instructions", "comparator": "Original matching-placebo record; actual group-specific supportive or subsequent treatment remains unverified", "endpoint": "Primary overall survival; distinguish median OS, death counts and HR", "duration": "Original median OS 7.6/7.3 months and TTP 3.0/2.6 months are endpoint time values; total follow-up or exposure and DCR assessment times remain unverified", "excluded_extensions": [ "Transferring DCR or TTP into OS benefit", "Certifying non-significant OS as zero effect, equivalence or safety", "Extension to other Child-Pugh classes, treatment lines, doses, products or current treatment strategies", "Medication, treatment-choice, substitution or discontinuation instructions", "Adding the same two sheets or endpoints as new independent trials or participants" ] }, "requirements": [ { "item_id": "N01", "question_type": "Evidence condition", "question": "Which existing question is being transferred to this sheet?", "needed": "Preserved draft distinguishing the existing question, record location and parent and sibling scopes", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Which existing question is being transferred to this sheet.", "application_exception": "The original candidate's boundary-review pending state is historical; review of the existing question boundary remains incomplete. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Which existing question is being transferred to this sheet\" and link them to original locations. The original candidate's boundary-review pending state is historical; review of the existing question boundary remains incomplete.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C01.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: An updated draft retaining the original question and record relationship if additional reports for the same question are supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The selected existing question is ‘Improved overall survival’; the question and existing verdict record are distinguished. The parent overall-survival draft's context is preserved in the complete copy, and other subclaims are not separate clinical trials.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. The original candidate's boundary-review pending state is historical; review of the existing question boundary remains incomplete. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "The original candidate's boundary-review pending state is historical; review of the existing question boundary remains incomplete.", "uncertainty": "The original candidate's boundary-review pending state is historical; review of the existing question boundary remains incomplete.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Preserved draft distinguishing the existing question, record location and parent and sibling scopes" }, { "item_id": "N02", "question_type": "Evidence condition", "question": "How are the subclaim grade and note distinguished from the parent score and axes?", "needed": "Separate locations for the selected subclaim wording and parent verdict history", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: How are the subclaim grade and note distinguished from the parent score and axes.", "application_exception": "Do not uniformly change subclaim C or D to D or inherit the parent's 34 points as a subclaim score.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"How are the subclaim grade and note distinguished from the parent score and axes\" and link them to original locations. Direct values for the subclaim score, status and axes are absent from the original.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C01, C09.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: A preserved copy separating complete original wording from the change event when the selected subclaim verdict itself is corrected", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The selected subclaim grade is D, with the note ‘The result was null, HR 1.05, P=.68.’ Subclaim score, status and axes fields are absent; parent grade D, score 34 and safety Caution are parent history.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Direct values for the subclaim score, status and axes are absent from the original. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Direct values for the subclaim score, status and axes are absent from the original.", "uncertainty": "Direct values for the subclaim score, status and axes are absent from the original.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Separate locations for the selected subclaim wording and parent verdict history" }, { "item_id": "N03", "question_type": "Evidence condition", "question": "Do the two sheets concern the same EVOLVE-1 report, trial and population?", "needed": "Relationship table for bibliography, registration, shared cohort and individual outcomes", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Do the two sheets concern the same EVOLVE-1 report, trial and population.", "application_exception": "Do not add the two sheets' 546 participants, 362/184 or two questions as independent replications or new participants.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Do the two sheets concern the same EVOLVE-1 report, trial and population\" and link them to original locations. Other report versions, follow-up results and current unique study or participant totals have not been established.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C02, E07, H07.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: An outcome-specific material list preserving the same-trial relationship when original or follow-up reports are supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The parent's evidence and citation lists each contain 1 record linking Zhu AX et al. 2014 EVOLVE-1, PMID 25058218 and NCT01035229. The two existing outcomes, time to progression and safety share this preserved report's context.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Other report versions, follow-up results and current unique study or participant totals have not been established. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Other report versions, follow-up results and current unique study or participant totals have not been established.", "uncertainty": "Other report versions, follow-up results and current unique study or participant totals have not been established.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Relationship table for bibliography, registration, shared cohort and individual outcomes" }, { "item_id": "N04", "question_type": "Evidence condition", "question": "What materials were actually read during this work?", "needed": "Material records separating the preserved summary from external original materials", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What materials were actually read during this work.", "application_exception": "Summary reading is not labeled as reading clinical original materials, and no access attempt is not converted into access failure.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What materials were actually read during this work\" and link them to original locations. External availability, acquisition, reading and link operation were not verified during this work.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C03.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Material records distinguishing reading level and dates when follow-up work that actually obtains new materials is authorized", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The specified complete parent verdict summary was read for production and the original preserved. External articles, abstracts, registration and plans remain unread and access was not attempted. The PubMed URL is the existing citation link.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. External availability, acquisition, reading and link operation were not verified during this work. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "External availability, acquisition, reading and link operation were not verified during this work.", "uncertainty": "External availability, acquisition, reading and link operation were not verified during this work.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Material records separating the preserved summary from external original materials" }, { "item_id": "N05", "question_type": "Evidence condition", "question": "What is the selected population and previous sorafenib-treatment scope?", "needed": "Recruitment criteria, baseline tables, previous treatment and distinctions between failure and intolerance", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What is the selected population and previous sorafenib-treatment scope.", "application_exception": "Age, sex, etiology, baseline tumor burden, specific inclusion or exclusion criteria and the respective proportions of failure and intolerance are absent from the preserved summary. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What is the selected population and previous sorafenib-treatment scope\" and link them to original locations. Age, sex, etiology, baseline tumor burden, specific inclusion or exclusion criteria and the respective proportions of failure and intolerance are absent from the preserved summary.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C04, E08.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Comparative materials specifying prespecified population-specific outcomes and scope in the same indication", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "EVOLVE-1 concerned Child-Pugh A patients with advanced hepatocellular carcinoma who failed or could not tolerate sorafenib. This scope is not transferred to all other liver diseases or treatment lines.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Age, sex, etiology, baseline tumor burden, specific inclusion or exclusion criteria and the respective proportions of failure and intolerance are absent from the preserved summary. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Age, sex, etiology, baseline tumor burden, specific inclusion or exclusion criteria and the respective proportions of failure and intolerance are absent from the preserved summary.", "uncertainty": "Age, sex, etiology, baseline tumor burden, specific inclusion or exclusion criteria and the respective proportions of failure and intolerance are absent from the preserved summary.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Recruitment criteria, baseline tables, previous treatment and distinctions between failure and intolerance" }, { "item_id": "N06", "question_type": "Evidence condition", "question": "How are 17 countries, 121 centers and participant distributions related?", "needed": "Center, country and recruitment flow and baseline distribution tables", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: How are 17 countries, 121 centers and participant distributions related.", "application_exception": "Recruitment counts by country or center, baseline balance, regional outcomes and follow-up differences remain unverified. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"How are 17 countries, 121 centers and participant distributions related\" and link them to original locations. Recruitment counts by country or center, baseline balance, regional outcomes and follow-up differences remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C04, E01, E07.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Link prespecified subgroup materials on regional or selection differences as outcomes within the same trial when available", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The preserved design is a randomized, double-blind, placebo-controlled phase 3 trial at 121 centers in 17 countries. Center and country counts are not participant or independent-trial counts.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Recruitment counts by country or center, baseline balance, regional outcomes and follow-up differences remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Recruitment counts by country or center, baseline balance, regional outcomes and follow-up differences remain unverified.", "uncertainty": "Recruitment counts by country or center, baseline balance, regional outcomes and follow-up differences remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Center, country and recruitment flow and baseline distribution tables" }, { "item_id": "N07", "question_type": "Evidence condition", "question": "What was the actual everolimus exposure and dose scope?", "needed": "Study product or formulation and nominal or actual exposure and change materials", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What was the actual everolimus exposure and dose scope.", "application_exception": "Nominal 7.5 mg/day is not converted into an individual dose or effects of other formulations or doses.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What was the actual everolimus exposure and dose scope\" and link them to original locations. Original formulation, detailed administration route, exposure duration, actual cumulative dose, dose reduction, discontinuation and adherence materials remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C05, E02, E08.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Research materials distinguishing exposure-specific results within the trial conditions when supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original study compared everolimus 7.5 mg/day plus best supportive care with placebo. This value is recorded only as historical research exposure, not medication or treatment instructions.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Original formulation, detailed administration route, exposure duration, actual cumulative dose, dose reduction, discontinuation and adherence materials remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Original formulation, detailed administration route, exposure duration, actual cumulative dose, dose reduction, discontinuation and adherence materials remain unverified.", "uncertainty": "Original formulation, detailed administration route, exposure duration, actual cumulative dose, dose reduction, discontinuation and adherence materials remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Study product or formulation and nominal or actual exposure and change materials" }, { "item_id": "N08", "question_type": "Evidence condition", "question": "How are placebo, supportive care and subsequent treatments distinguished?", "needed": "Group-specific concomitant and subsequent treatments, departures and analysis handling tables", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: How are placebo, supportive care and subsequent treatments distinguished.", "application_exception": "Matching placebo alone does not establish that all concomitant and subsequent treatments were identical.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"How are placebo, supportive care and subsequent treatments distinguished\" and link them to original locations. Actual supportive-care balance, subsequent anticancer or rescue therapy, departures, crossover and analysis handling remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C05, E02.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Follow-up materials linking subsequent-treatment or crossover information to the original randomized comparison", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The preserved summary records matching placebo and everolimus plus best supportive care as study conditions. Specific control-group and group-specific supportive care remain a separate scope to document.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Actual supportive-care balance, subsequent anticancer or rescue therapy, departures, crossover and analysis handling remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Actual supportive-care balance, subsequent anticancer or rescue therapy, departures, crossover and analysis handling remain unverified.", "uncertainty": "Actual supportive-care balance, subsequent anticancer or rescue therapy, departures, crossover and analysis handling remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Group-specific concomitant and subsequent treatments, departures and analysis handling tables" }, { "item_id": "N09", "question_type": "Evidence condition", "question": "What were randomization, full-analysis and group denominators?", "needed": "Allocation-to-exposure-to-analysis flow, endpoint denominators and exclusion reasons", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What were randomization, full-analysis and group denominators.", "application_exception": "The full-analysis description is not extended to complete observation of all imaging or safety data or current ITT certification.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What were randomization, full-analysis and group denominators\" and link them to original locations. Endpoint-specific measurable, completed, followed and safety-analysis denominators require separate tables.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C07, E04.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original reports distinguishing analysis populations for each outcome within the same allocated population", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Preserve the recorded sample of 546 randomized and analyzed participants: 362 everolimus versus 184 placebo. The existing research description records 2:1 allocation and inclusion of everyone in the full analysis population.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Endpoint-specific measurable, completed, followed and safety-analysis denominators require separate tables. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Endpoint-specific measurable, completed, followed and safety-analysis denominators require separate tables.", "uncertainty": "Endpoint-specific measurable, completed, followed and safety-analysis denominators require separate tables.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Allocation-to-exposure-to-analysis flow, endpoint denominators and exclusion reasons" }, { "item_id": "N10", "question_type": "Evidence condition", "question": "What is the scope of handling missingness, follow-up loss and discontinuation?", "needed": "Endpoint-specific missingness or censoring, discontinuation, analysis plans and sensitivity results", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What is the scope of handling missingness, follow-up loss and discontinuation.", "application_exception": "Group-specific follow-up loss, administrative censoring, missingness reasons, sensitivity analyses and observation after discontinuation are absent from the original summary. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What is the scope of handling missingness, follow-up loss and discontinuation\" and link them to original locations. Group-specific follow-up loss, administrative censoring, missingness reasons, sensitivity analyses and observation after discontinuation are absent from the original summary.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C07, E04, H06.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Supplementary reports of missingness or follow-up materials based on actual flow and original analysis assumptions", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Preserve the original summary stating that all 546 participants were included in the full analysis population. Death, progression, medication discontinuation and loss to follow-up are different events.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Group-specific follow-up loss, administrative censoring, missingness reasons, sensitivity analyses and observation after discontinuation are absent from the original summary. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Group-specific follow-up loss, administrative censoring, missingness reasons, sensitivity analyses and observation after discontinuation are absent from the original summary.", "uncertainty": "Group-specific follow-up loss, administrative censoring, missingness reasons, sensitivity analyses and observation after discontinuation are absent from the original summary.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Endpoint-specific missingness or censoring, discontinuation, analysis plans and sensitivity results" }, { "item_id": "N11", "question_type": "Evidence condition", "question": "What original record describes the allocation process?", "needed": "Original locations of allocation or concealment procedures and baseline tables", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What original record describes the allocation process.", "application_exception": "Original details of random-number generation, stratification variables, sequence access, operational roles and baseline balance remain externally unread. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What original record describes the allocation process\" and link them to original locations. Original details of random-number generation, stratification variables, sequence access, operational roles and baseline balance remain externally unread.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E01.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Materials linking allocation history and original analysis when registration, protocols or reports are actually supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The existing research description preserves the quotation that participants were registered using an interactive voice- or web-response system and randomized. The 2:1 allocation is the group allocation ratio within the same trial.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Original details of random-number generation, stratification variables, sequence access, operational roles and baseline balance remain externally unread. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Original details of random-number generation, stratification variables, sequence access, operational roles and baseline balance remain externally unread.", "uncertainty": "Original details of random-number generation, stratification variables, sequence access, operational roles and baseline balance remain externally unread.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original locations of allocation or concealment procedures and baseline tables" }, { "item_id": "N12", "question_type": "Evidence condition", "question": "Whom and which procedures does the double-blinding record concern?", "needed": "Blinded parties, maintenance or unblinding and endpoint-specific assessment procedures", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Whom and which procedures does the double-blinding record concern.", "application_exception": "Specific blinding of participants, clinicians, outcome assessors and statisticians, unblinding, success and imaging interpretation remain unverified. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Whom and which procedures does the double-blinding record concern\" and link them to original locations. Specific blinding of participants, clinicians, outcome assessors and statisticians, unblinding, success and imaging interpretation remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E01, E03.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Distinguish blinding scope through original materials reporting actual assessment conditions for each outcome", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Preserve the original records ‘randomized, double-blind’ and ‘matching placebo’. A blinding description is not automatically identical to current outcome-specific measurement procedures.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Specific blinding of participants, clinicians, outcome assessors and statisticians, unblinding, success and imaging interpretation remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Specific blinding of participants, clinicians, outcome assessors and statisticians, unblinding, success and imaging interpretation remain unverified.", "uncertainty": "Specific blinding of participants, clinicians, outcome assessors and statisticians, unblinding, success and imaging interpretation remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Blinded parties, maintenance or unblinding and endpoint-specific assessment procedures" }, { "item_id": "N13", "question_type": "Evidence condition", "question": "Are randomized design and current bias judgments separated?", "needed": "Original details of design, allocation, missingness, measurement and selective reporting", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Are randomized design and current bias judgments separated.", "application_exception": "Parent B0 and the true large-hard-endpoint-RCT marker are not automatically inherited as fulfillment of conditions for both subclaims.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Are randomized design and current bias judgments separated\" and link them to original locations. Official outcome-specific risk assessment and original-document comparison remain within the user's review scope.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E01, E03, E04, E06.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: An updated draft documenting outcome-specific design information when additional original materials are supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The parent historically recorded a large randomized trial with a hard endpoint and four B0 evidence items. No RoB2 assessment or new bias grade is performed during this production work.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Official outcome-specific risk assessment and original-document comparison remain within the user's review scope. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Official outcome-specific risk assessment and original-document comparison remain within the user's review scope.", "uncertainty": "Official outcome-specific risk assessment and original-document comparison remain within the user's review scope.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original details of design, allocation, missingness, measurement and selective reporting" }, { "item_id": "N14", "question_type": "Evidence condition", "question": "What is the effect of interest for adherence, treatment changes and the randomized comparison?", "needed": "Effect of interest, analysis population and handling of adherence or treatment changes", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What is the effect of interest for adherence, treatment changes and the randomized comparison.", "application_exception": "PP or adherence effects, actual dose intensity and group-specific treatment-change or subsequent-treatment analyses remain unverified. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What is the effect of interest for adherence, treatment changes and the randomized comparison\" and link them to original locations. PP or adherence effects, actual dose intensity and group-specific treatment-change or subsequent-treatment analyses remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E02, E04.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Supplementary reports from the same trial explicitly linking analyses different from the randomized comparison", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Preserved values concern the randomized everolimus-versus-placebo comparison. Nominal research exposure is distinguished from actual medication use and maintenance effects.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. PP or adherence effects, actual dose intensity and group-specific treatment-change or subsequent-treatment analyses remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "PP or adherence effects, actual dose intensity and group-specific treatment-change or subsequent-treatment analyses remain unverified.", "uncertainty": "PP or adherence effects, actual dose intensity and group-specific treatment-change or subsequent-treatment analyses remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Effect of interest, analysis population and handling of adherence or treatment changes" }, { "item_id": "N15", "question_type": "Evidence condition", "question": "Do outcome collection and assessment procedures fit the actual endpoints?", "needed": "Endpoint-specific definitions, methods, assessors, schedules and missing measurements", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Do outcome collection and assessment procedures fit the actual endpoints.", "application_exception": "Death ascertainment routes, imaging criteria, assessment schedules, central review, assessor blinding and repeated assessments remain unverified. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Do outcome collection and assessment procedures fit the actual endpoints\" and link them to original locations. Death ascertainment routes, imaging criteria, assessment schedules, central review, assessor blinding and repeated assessments remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C06, E03.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original reports or appendices linking actual endpoint measurement procedures to reported values", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Overall survival, disease control and time to progression are different measured outcomes within the same trial. The double-blind design is preserved, but outcome-specific interpretation or ascertainment methods are separately required.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Death ascertainment routes, imaging criteria, assessment schedules, central review, assessor blinding and repeated assessments remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Death ascertainment routes, imaging criteria, assessment schedules, central review, assessor blinding and repeated assessments remain unverified.", "uncertainty": "Death ascertainment routes, imaging criteria, assessment schedules, central review, assessor blinding and repeated assessments remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Endpoint-specific definitions, methods, assessors, schedules and missing measurements" }, { "item_id": "N16", "question_type": "Evidence condition", "question": "Can analysis models, adjustment and between-group or within-group outcomes be distinguished?", "needed": "Estimate definitions in statistical methods, SAP and original outcome tables", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Can analysis models, adjustment and between-group or within-group outcomes be distinguished.", "application_exception": "HR models, adjustment variables, stratification, assumptions, proportion-comparison tests and sensitivity analyses remain unverified. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Can analysis models, adjustment and between-group or within-group outcomes be distinguished\" and link them to original locations. HR models, adjustment variables, stratification, assumptions, proportion-comparison tests and sensitivity analyses remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C06, E04, E05.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Additional materials publishing original models and distinguishing adjusted from unadjusted outcomes", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Preserved numbers are between-group HR and P comparisons and group-specific medians or proportions. Group-specific medians or proportions are not written as within-group changes.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. HR models, adjustment variables, stratification, assumptions, proportion-comparison tests and sensitivity analyses remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "HR models, adjustment variables, stratification, assumptions, proportion-comparison tests and sensitivity analyses remain unverified.", "uncertainty": "HR models, adjustment variables, stratification, assumptions, proportion-comparison tests and sensitivity analyses remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Estimate definitions in statistical methods, SAP and original outcome tables" }, { "item_id": "N17", "question_type": "Evidence condition", "question": "What is the history of prespecified primary overall survival and registration?", "needed": "Original locations of primary endpoints, analyses and times in registration versions, protocol, SAP and report", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What is the history of prespecified primary overall survival and registration.", "application_exception": "Original registration-agreement wording is not labeled as current registration reading or prespecification certification.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What is the history of prespecified primary overall survival and registration\" and link them to original locations. Current registration documents, change history, protocol and SAP were not read or compared.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E06, C09.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: A linked draft distinguishing prespecification and reasons for changes in follow-up work that receives actual plan materials", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Preserve the existing research description's quotation ‘The primary end point was overall survival’ and recorded agreement with NCT01035229. The registration number is the original identifier in the existing evidence list.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Current registration documents, change history, protocol and SAP were not read or compared. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Current registration documents, change history, protocol and SAP were not read or compared.", "uncertainty": "Current registration documents, change history, protocol and SAP were not read or compared.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original locations of primary endpoints, analyses and times in registration versions, protocol, SAP and report" }, { "item_id": "N18", "question_type": "Evidence condition", "question": "What is the scope of secondary positivity after primary failure and multiplicity?", "needed": "Complete primary or secondary outcome lists and multiplicity plans in protocol, SAP and registration", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What is the scope of secondary positivity after primary failure and multiplicity.", "application_exception": "P=.01 is not automatically promoted into confirmatory success, survival benefit or a new grade.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What is the scope of secondary positivity after primary failure and multiplicity\" and link them to original locations. Complete secondary endpoint lists, hierarchical testing, multiplicity adjustment, prespecified confirmatory status and changes remain externally unread.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E06, C08, E09.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: A draft distinguishing the statistical scope of secondary outcomes when plan and result materials from the same trial are supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The existing reader answer and counterview record positive secondary disease control after failure of primary overall survival. Preserve the parent's primary-failed-secondary-positive marker as true.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Complete secondary endpoint lists, hierarchical testing, multiplicity adjustment, prespecified confirmatory status and changes remain externally unread. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Complete secondary endpoint lists, hierarchical testing, multiplicity adjustment, prespecified confirmatory status and changes remain externally unread.", "uncertainty": "Complete secondary endpoint lists, hierarchical testing, multiplicity adjustment, prespecified confirmatory status and changes remain externally unread.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Complete primary or secondary outcome lists and multiplicity plans in protocol, SAP and registration" }, { "item_id": "N19", "question_type": "Evidence condition", "question": "Are direct materials available for subgroups, responders, dose and persistence questions?", "needed": "Prespecified subgroup, interaction and exposure-specific original outcomes and plans", "role": "Supplementary; required for extension", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Are direct materials available for subgroups, responders, dose and persistence questions.", "application_exception": "Prespecified subgroups, interactions, molecular markers, direct dose comparisons and outcomes after treatment discontinuation remain unverified. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Are direct materials available for subgroups, responders, dose and persistence questions\" and link them to original locations. Prespecified subgroups, interactions, molecular markers, direct dose comparisons and outcomes after treatment discontinuation remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E08, E07.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Link additional research materials with explicit population or exposure, distinguishing the same from separate study families", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The parent's population is Child-Pugh A after sorafenib failure or intolerance, and research exposure is 7.5 mg/day. Molecular selection, responders and other-dose or persistence effects are not separately supplied.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Prespecified subgroups, interactions, molecular markers, direct dose comparisons and outcomes after treatment discontinuation remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Prespecified subgroups, interactions, molecular markers, direct dose comparisons and outcomes after treatment discontinuation remain unverified.", "uncertainty": "Prespecified subgroups, interactions, molecular markers, direct dose comparisons and outcomes after treatment discontinuation remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Prespecified subgroup, interaction and exposure-specific original outcomes and plans" }, { "item_id": "N20", "question_type": "Evidence condition", "question": "Can this scope be extended to other liver function, treatment lines or long-term harms?", "needed": "Direct comparisons and safety materials by extended population, exposure and duration", "role": "Supplementary; required for extension", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Can this scope be extended to other liver function, treatment lines or long-term harms.", "application_exception": "No new search was conducted for direct materials on other populations or exposures, longer observation, rare harms or current treatment combinations. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Can this scope be extended to other liver function, treatment lines or long-term harms\" and link them to original locations. No new search was conducted for direct materials on other populations or exposures, longer observation, rare harms or current treatment combinations.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C04, E08, H08.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Link materials for separate indications or durations with explicit differences in applicability from the existing results when supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The current draft is limited to historical EVOLVE-1: Child-Pugh A advanced hepatocellular carcinoma after sorafenib. Other liver function, populations, treatment lines and current strategies are outside this direct result's scope.", "condition_status": "Unverified", "status_reason": "Direct details of this condition were not verified within the current preserved-summary and externally unread scope. No new search was conducted for direct materials on other populations or exposures, longer observation, rare harms or current treatment combinations. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "No new search was conducted for direct materials on other populations or exposures, longer observation, rare harms or current treatment combinations.", "uncertainty": "No new search was conducted for direct materials on other populations or exposures, longer observation, rare harms or current treatment combinations.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Direct comparisons and safety materials by extended population, exposure and duration" }, { "item_id": "N21", "question_type": "Evidence condition", "question": "What are the selected overall-survival definition, hierarchy and time origin?", "needed": "OS definition, time origin, death ascertainment and planned or final follow-up materials", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What are the selected overall-survival definition, hierarchy and time origin.", "application_exception": "Time origin, death ascertainment, administrative closure, planned event counts and follow-up duration details remain unverified. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What are the selected overall-survival definition, hierarchy and time origin\" and link them to original locations. Time origin, death ascertainment, administrative closure, planned event counts and follow-up duration details remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C06, E06, E09.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original materials linking OS definitions, analyses and follow-up reports from the same trial", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The selected question is improved overall survival, and the existing evidence-list endpoint is primary overall survival. Disease control, time to progression and stomatitis are separate outcomes.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Time origin, death ascertainment, administrative closure, planned event counts and follow-up duration details remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Time origin, death ascertainment, administrative closure, planned event counts and follow-up duration details remain unverified.", "uncertainty": "Time origin, death ascertainment, administrative closure, planned event counts and follow-up duration details remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "OS definition, time origin, death ascertainment and planned or final follow-up materials" }, { "item_id": "N22", "question_type": "Evidence condition", "question": "What do median OS values of 7.6 versus 7.3 months represent?", "needed": "Group-specific median survival, CI, survival curves and data cutoff", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What do median OS values of 7.6 versus 7.3 months represent.", "application_exception": "Do not subtract the two medians to create a new benefit or harm duration or present them as study follow-up duration.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What do median OS values of 7.6 versus 7.3 months represent\" and link them to original locations. Median CIs, estimation methods, data cutoff and total follow-up duration are absent from the preserved summary.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C06, E05.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original OS tables publishing medians alongside between-group estimates", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Median overall survival for everolimus versus placebo was 7.6 versus 7.3 months. These are group-specific median survival times, not total follow-up duration or within-group improvement.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Median CIs, estimation methods, data cutoff and total follow-up duration are absent from the preserved summary. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Median CIs, estimation methods, data cutoff and total follow-up duration are absent from the preserved summary.", "uncertainty": "Median CIs, estimation methods, data cutoff and total follow-up duration are absent from the preserved summary.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Group-specific median survival, CI, survival curves and data cutoff" }, { "item_id": "N23", "question_type": "Evidence condition", "question": "What is the original direction of the OS HR, 95% CI and P?", "needed": "Original OS tables, SAP, HR analysis methods and intervals", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What is the original direction of the OS HR, 95% CI and P.", "application_exception": "HR is not converted into a survival proportion, RR or change in mean or median survival.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What is the original direction of the OS HR, 95% CI and P\" and link them to original locations. Complete original details of HR models, adjustment, stratification, assumption checks and prespecified judgment criteria remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C06, C07, C08, E04, E05.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Additional reports linking actual HR analysis definitions, plans and outcomes", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Preserve OS HR 1.05 (95% CI 0.86~1.27), P=.68. The original subclaim note and parent describe a null result for improved overall survival.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Complete original details of HR models, adjustment, stratification, assumption checks and prespecified judgment criteria remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Complete original details of HR models, adjustment, stratification, assumption checks and prespecified judgment criteria remain unverified.", "uncertainty": "Complete original details of HR models, adjustment, stratification, assumption checks and prespecified judgment criteria remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original OS tables, SAP, HR analysis methods and intervals" }, { "item_id": "N24", "question_type": "Evidence condition", "question": "What are the death events, participant denominators and original proportions?", "needed": "Death counts, timing, populations at risk, censoring and original tables", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What are the death events, participant denominators and original proportions.", "application_exception": "Do not add original death counts into new totals or risk differences or count participants without deaths as losses.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What are the death events, participant denominators and original proportions\" and link them to original locations. Cause-specific death categories, censored counts, populations at risk by time and completeness of death data remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C07, E04.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original OS materials publishing death and follow-up data for the same allocated population", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The existing reader answer records deaths of 303/362 (83.7%) versus 151/184 (82.1%). Preserve group-specific events, denominators and original proportions together.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Cause-specific death categories, censored counts, populations at risk by time and completeness of death data remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Cause-specific death categories, censored counts, populations at risk by time and completeness of death data remain unverified.", "uncertainty": "Cause-specific death categories, censored counts, populations at risk by time and completeness of death data remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Death counts, timing, populations at risk, censoring and original tables" }, { "item_id": "N25", "question_type": "Evidence condition", "question": "Does analysis of all 546 participants mean complete OS follow-up?", "needed": "OS analysis population, follow-up loss, censoring tables and sensitivity analyses", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Does analysis of all 546 participants mean complete OS follow-up.", "application_exception": "Do not subtract non-death participants or declare everyone missing or completely followed.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Does analysis of all 546 participants mean complete OS follow-up\" and link them to original locations. Specific survival, censoring, administrative closure and follow-up loss cannot be verified from the full-analysis description alone.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C07, E04.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original tables from the same trial specifying differences between full analysis and actual follow-up information", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Inclusion of everyone in the full analysis population records the original analysis population. Distinguish 303/362 and 151/184 death counts from inclusion in analysis.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Specific survival, censoring, administrative closure and follow-up loss cannot be verified from the full-analysis description alone. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Specific survival, censoring, administrative closure and follow-up loss cannot be verified from the full-analysis description alone.", "uncertainty": "Specific survival, censoring, administrative closure and follow-up loss cannot be verified from the full-analysis description alone.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "OS analysis population, follow-up loss, censoring tables and sensitivity analyses" }, { "item_id": "N26", "question_type": "Evidence condition", "question": "What were the survival risk sets, censoring and time models?", "needed": "Survival curves, risk-set tables, censoring rules, models and SAP", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What were the survival risk sets, censoring and time models.", "application_exception": "Proportional-hazards assumptions, censoring rules, stratification or adjustment variables, time-dependent effects and post hoc sensitivity remain unverified. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What were the survival risk sets, censoring and time models\" and link them to original locations. Proportional-hazards assumptions, censoring rules, stratification or adjustment variables, time-dependent effects and post hoc sensitivity remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E04, E05, C07.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Same-trial materials separately reporting original survival-analysis assumptions and sensitivity", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Original values are median OS and the between-group HR. Actual risk sets by time, censoring and model information are not separately available in the preserved summary.", "condition_status": "Unverified", "status_reason": "Direct details of this condition were not verified within the current preserved-summary and externally unread scope. Proportional-hazards assumptions, censoring rules, stratification or adjustment variables, time-dependent effects and post hoc sensitivity remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Proportional-hazards assumptions, censoring rules, stratification or adjustment variables, time-dependent effects and post hoc sensitivity remain unverified.", "uncertainty": "Proportional-hazards assumptions, censoring rules, stratification or adjustment variables, time-dependent effects and post hoc sensitivity remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Survival curves, risk-set tables, censoring rules, models and SAP" }, { "item_id": "N27", "question_type": "Evidence condition", "question": "Is non-significant OS being converted into zero effect or equivalence?", "needed": "Original intervals, test purpose, clinical importance and design limitations", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Is non-significant OS being converted into zero effect or equivalence.", "application_exception": "Null-result wording is not extended into exactly zero effect, equivalence or absence of harm.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Is non-significant OS being converted into zero effect or equivalence\" and link them to original locations. Equivalence or noninferiority plans, justified equivalence margins and exclusion of every effect magnitude have not been verified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C08, E05.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Statistical materials clearly publishing original judgment criteria and interval interpretation", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "HR 1.05 (95% CI 0.86~1.27), P=.68 records failure of the original improved-survival claim. The parent explicitly states that the confidence interval retained possible benefit.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Equivalence or noninferiority plans, justified equivalence margins and exclusion of every effect magnitude have not been verified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Equivalence or noninferiority plans, justified equivalence margins and exclusion of every effect magnitude have not been verified.", "uncertainty": "Equivalence or noninferiority plans, justified equivalence margins and exclusion of every effect magnitude have not been verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original intervals, test purpose, clinical importance and design limitations" }, { "item_id": "N28", "question_type": "Evidence condition", "question": "What is the threshold for an OS difference important to patients?", "needed": "Planned important difference, power or event-count assumptions and patient-outcome criteria", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What is the threshold for an OS difference important to patients.", "application_exception": "A sample of 546 or a hard endpoint does not by itself establish exclusion of every important effect.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What is the threshold for an OS difference important to patients\" and link them to original locations. Prespecified important differences, patient values, power and event-count assumptions remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E05.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Link justified importance criteria from the original plan with the relevant interval when supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Original materials present a hard overall-survival endpoint, HR and interval. A separate clinically important OS difference threshold is absent from this summary.", "condition_status": "Unverified", "status_reason": "Direct details of this condition were not verified within the current preserved-summary and externally unread scope. Prespecified important differences, patient values, power and event-count assumptions remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Prespecified important differences, patient values, power and event-count assumptions remain unverified.", "uncertainty": "Prespecified important differences, patient values, power and event-count assumptions remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Planned important difference, power or event-count assumptions and patient-outcome criteria" }, { "item_id": "N29", "question_type": "Evidence condition", "question": "Is positive secondary disease control kept from being transferred into OS benefit?", "needed": "Original DCR tables, definitions, plans and boundaries from OS", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Is positive secondary disease control kept from being transferred into OS benefit.", "application_exception": "No new difference beyond the original 11%p is calculated, and positive DCR is not changed into positive OS.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Is positive secondary disease control kept from being transferred into OS benefit\" and link them to original locations. DCR definitions, assessment times, denominators, CI, multiplicity and survival-prediction or mediation validation remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C08, E06, E09.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Reports linking DCR and OS within the same trial through their respective definitions, times and denominators", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Disease control was 56.1% versus 45.1% (P=.01); preserve the existing counterpoint's 11%p difference wording. This was a secondary result after failure of primary survival.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. DCR definitions, assessment times, denominators, CI, multiplicity and survival-prediction or mediation validation remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "DCR definitions, assessment times, denominators, CI, multiplicity and survival-prediction or mediation validation remain unverified.", "uncertainty": "DCR definitions, assessment times, denominators, CI, multiplicity and survival-prediction or mediation validation remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original DCR tables, definitions, plans and boundaries from OS" }, { "item_id": "N30", "question_type": "Evidence condition", "question": "How does time to progression differ from OS?", "needed": "TTP definitions, models, original results and distinction from OS", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: How does time to progression differ from OS.", "application_exception": "Time to progression is not converted into PFS, survival benefit or a new duration difference.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"How does time to progression differ from OS\" and link them to original locations. Progression definitions, ascertainment, censoring or death handling, denominators, original P and analysis plans remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C06, C08, E09.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Same-trial materials separately publishing progression or death analysis definitions and follow-up", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Time to progression was a separate original result: 3.0 versus 2.6 months, HR 0.93 (95% CI 0.75~1.15). Its name is not interchanged with overall survival, DCR or progression-free survival.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Progression definitions, ascertainment, censoring or death handling, denominators, original P and analysis plans remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Progression definitions, ascertainment, censoring or death handling, denominators, original P and analysis plans remain unverified.", "uncertainty": "Progression definitions, ascertainment, censoring or death handling, denominators, original P and analysis plans remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "TTP definitions, models, original results and distinction from OS" }, { "item_id": "N31", "question_type": "Evidence condition", "question": "What was the original all-grade stomatitis comparison?", "needed": "Original stomatitis tables, safety population, grading criteria and duration", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What was the original all-grade stomatitis comparison.", "application_exception": "Stomatitis event counts, safety denominators, collection or classification, times, CI and P remain unverified. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What was the original all-grade stomatitis comparison\" and link them to original locations. Stomatitis event counts, safety denominators, collection or classification, times, CI and P remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E10, H01, H03, H04.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original safety materials linking stomatitis in the same exposed population with denominators and duration", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original record reports all-grade stomatitis of 39.6% versus 4.9%. This is a safety outcome distinct from tumor control or survival.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Stomatitis event counts, safety denominators, collection or classification, times, CI and P remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Stomatitis event counts, safety denominators, collection or classification, times, CI and P remain unverified.", "uncertainty": "Stomatitis event counts, safety denominators, collection or classification, times, CI and P remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original stomatitis tables, safety population, grading criteria and duration" }, { "item_id": "N32", "question_type": "Evidence condition", "question": "What were the grade 3 or 4 anemia comparison and original statistical level?", "needed": "Anemia safety tables, denominators or duration, classification and baseline status", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What were the grade 3 or 4 anemia comparison and original statistical level.", "application_exception": "Descriptive proportions are not newly calculated into significant risk increases, no-difference tests or incidence rates.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What were the grade 3 or 4 anemia comparison and original statistical level\" and link them to original locations. Anemia event counts, denominators, baseline anemia, grading criteria, between-group CI or P and timing remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E10, H01, H03, H04.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Materials publishing hematologic harms from the same trial at the original population, timing and analysis level", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Grade 3 or 4 anemia was 7.8% versus 3.3%, with the original safety comparison recorded as descriptive statistics.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Anemia event counts, denominators, baseline anemia, grading criteria, between-group CI or P and timing remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Anemia event counts, denominators, baseline anemia, grading criteria, between-group CI or P and timing remain unverified.", "uncertainty": "Anemia event counts, denominators, baseline anemia, grading criteria, between-group CI or P and timing remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Anemia safety tables, denominators or duration, classification and baseline status" }, { "item_id": "N33", "question_type": "Evidence condition", "question": "What were the original grade 3 or 4 asthenia and decreased-appetite values?", "needed": "Original tables, denominators, grading, collection and timing for each safety event", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What were the original grade 3 or 4 asthenia and decreased-appetite values.", "application_exception": "Do not merge the two symptoms into a new composite event, participant total or risk difference.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What were the original grade 3 or 4 asthenia and decreased-appetite values\" and link them to original locations. Event-specific denominators, participants versus event counts, co-occurring events, causes or timing, CI or P and classifications remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions H01, H03, H04, E10.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Safety materials reporting asthenia and decreased appetite as separate events under the same exposure", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Preserve grade 3 or 4 asthenia of 7.8% versus 5.5% and decreased appetite of 6.1% versus 0.5% separately. Original safety comparisons were descriptive statistics.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Event-specific denominators, participants versus event counts, co-occurring events, causes or timing, CI or P and classifications remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Event-specific denominators, participants versus event counts, co-occurring events, causes or timing, CI or P and classifications remain unverified.", "uncertainty": "Event-specific denominators, participants versus event counts, co-occurring events, causes or timing, CI or P and classifications remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original tables, denominators, grading, collection and timing for each safety event" }, { "item_id": "N34", "question_type": "Evidence condition", "question": "How are asymptomatic hepatitis B reactivation and discontinuation distinguished?", "needed": "HBV testing criteria, populations at risk, group denominators or follow-up and original discontinuation tables", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: How are asymptomatic hepatitis B reactivation and discontinuation distinguished.", "application_exception": "Do not divide 29/10 or 3 discontinuations by full allocated denominators to calculate new proportions or risks.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"How are asymptomatic hepatitis B reactivation and discontinuation distinguished\" and link them to original locations. Reactivation criteria, baseline HBV or at-risk denominators, testing times, prophylaxis, discontinuation timing or attribution and CI or P remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions H01, H02, H03, H04, H05.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Safety materials linking HBV reactivation and discontinuation under the same exposure with populations at risk", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original record reports asymptomatic hepatitis B reactivation by central laboratory testing in 29 versus 10 participants, and discontinuation in 3 everolimus participants. Asymptomatic test results and medication discontinuation are separate events.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Reactivation criteria, baseline HBV or at-risk denominators, testing times, prophylaxis, discontinuation timing or attribution and CI or P remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Reactivation criteria, baseline HBV or at-risk denominators, testing times, prophylaxis, discontinuation timing or attribution and CI or P remain unverified.", "uncertainty": "Reactivation criteria, baseline HBV or at-risk denominators, testing times, prophylaxis, discontinuation timing or attribution and CI or P remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "HBV testing criteria, populations at risk, group denominators or follow-up and original discontinuation tables" }, { "item_id": "N35", "question_type": "Evidence condition", "question": "What is the scope of safety denominators, exposure duration and complete collection?", "needed": "Safety analysis definitions, exposure, all-event tables and collection or follow-up materials", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What is the scope of safety denominators, exposure duration and complete collection.", "application_exception": "Safety populations, actual exposure durations, event-specific populations at risk, collection or follow-up, post-discontinuation events, losses and rare harms remain unverified. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What is the scope of safety denominators, exposure duration and complete collection\" and link them to original locations. Safety populations, actual exposure durations, event-specific populations at risk, collection or follow-up, post-discontinuation events, losses and rare harms remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions H02, H04, H06, H08.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original reports from the same trial specifying safety populations, timing and missingness", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The parent records stomatitis, hematologic or hepatic outcomes and Caution status. Distinguish the full randomized-analysis denominator from safety exposure or assessment denominators.", "condition_status": "Unverified", "status_reason": "Direct details of this condition were not verified within the current preserved-summary and externally unread scope. Safety populations, actual exposure durations, event-specific populations at risk, collection or follow-up, post-discontinuation events, losses and rare harms remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Safety populations, actual exposure durations, event-specific populations at risk, collection or follow-up, post-discontinuation events, losses and rare harms remain unverified.", "uncertainty": "Safety populations, actual exposure durations, event-specific populations at risk, collection or follow-up, post-discontinuation events, losses and rare harms remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Safety analysis definitions, exposure, all-event tables and collection or follow-up materials" }, { "item_id": "N36", "question_type": "Evidence condition", "question": "What are baseline disease, concurrent treatment and alternative causes of harms?", "needed": "Baseline risks, concomitant or subsequent treatments, event attribution and original analyses", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What are baseline disease, concurrent treatment and alternative causes of harms.", "application_exception": "Do not newly assert that other causes were absent or all events were caused by everolimus.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What are baseline disease, concurrent treatment and alternative causes of harms\" and link them to original locations. Baseline liver disease or HBV, anemia, concurrent medications, subsequent treatment, alternative causes and group-specific adjustment remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions H05, E02, E10.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Supplementary safety materials separately publishing baseline disease and exposure or event relationships", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Advanced hepatocellular carcinoma, Child-Pugh A, prior sorafenib failure or intolerance and supportive care are the original population or exposure context. Detailed medication attribution of recorded events is separate.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Baseline liver disease or HBV, anemia, concurrent medications, subsequent treatment, alternative causes and group-specific adjustment remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Baseline liver disease or HBV, anemia, concurrent medications, subsequent treatment, alternative causes and group-specific adjustment remain unverified.", "uncertainty": "Baseline liver disease or HBV, anemia, concurrent medications, subsequent treatment, alternative causes and group-specific adjustment remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Baseline risks, concomitant or subsequent treatments, event attribution and original analyses" }, { "item_id": "N37", "question_type": "Evidence condition", "question": "Who supplied research funding, study medication and placebo?", "needed": "Original funding, product supply, contracts and disclosed interests", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Who supplied research funding, study medication and placebo.", "application_exception": "Original contracts, funding details, complete individual-interest disclosures and current changes remain externally unread. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Who supplied research funding, study medication and placebo\" and link them to original locations. Original contracts, funding details, complete individual-interest disclosures and current changes remain externally unread.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C10.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original materials publishing actual-report funding, product supply and roles together", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Preserve Novartis Pharmaceuticals sponsorship, study medication or placebo supply, data management, statistical analysis and writing support from original funding information and narrative.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Original contracts, funding details, complete individual-interest disclosures and current changes remain externally unread. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Original contracts, funding details, complete individual-interest disclosures and current changes remain externally unread.", "uncertainty": "Original contracts, funding details, complete individual-interest disclosures and current changes remain externally unread.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original funding, product supply, contracts and disclosed interests" }, { "item_id": "N38", "question_type": "Evidence condition", "question": "How did the sponsor participate in design, data collection and analysis?", "needed": "Design, collection and analysis role declarations, data access and statistical responsibility", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: How did the sponsor participate in design, data collection and analysis.", "application_exception": "Sponsor involvement alone does not justify deleting original numbers or deriving a new null effect or bias magnitude.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"How did the sponsor participate in design, data collection and analysis\" and link them to original locations. Specific scope of full data access, original statistical responsibility, independent reanalysis and operational contracts remains unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C10, E04.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original declarations or supplementary materials specifying reported roles and the scope of actual analysis disclosure", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The existing research description records Novartis participation in design, collection through its data-management system and analysis by its statistical team.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Specific scope of full data access, original statistical responsibility, independent reanalysis and operational contracts remains unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Specific scope of full data access, original statistical responsibility, independent reanalysis and operational contracts remains unverified.", "uncertainty": "Specific scope of full data access, original statistical responsibility, independent reanalysis and operational contracts remains unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Design, collection and analysis role declarations, data access and statistical responsibility" }, { "item_id": "N39", "question_type": "Evidence condition", "question": "What were employee-author, writing and submission-decision roles?", "needed": "Author employment or COI, contributions, writing and publication-role declarations", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What were employee-author, writing and submission-decision roles.", "application_exception": "Complete individual-author COI, writing or approval and submission-authority contracts and role changes remain unverified. Preserve both relevant summary information and unverified matters; empty values are not filled with new numbers or verdicts.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What were employee-author, writing and submission-decision roles\" and link them to original locations. Complete individual-author COI, writing or approval and submission-authority contracts and role changes remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C10.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Materials linking original author or sponsor roles and disclosed interests", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The preserved summary records employee authors participating in interpretation, writing and submission decisions, and Novartis paying ApotheCom's medical-writing costs.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Complete individual-author COI, writing or approval and submission-authority contracts and role changes remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Complete individual-author COI, writing or approval and submission-authority contracts and role changes remain unverified.", "uncertainty": "Complete individual-author COI, writing or approval and submission-authority contracts and role changes remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Author employment or COI, contributions, writing and publication-role declarations" }, { "item_id": "N40", "question_type": "Evidence condition", "question": "What is the actual scope of independent replication or separate safety materials?", "needed": "Reports, study families, COI, shared outcomes and contrary-material lists", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: What is the actual scope of independent replication or separate safety materials.", "application_exception": "One literature record or two existing sheets are not converted into current worldwide trial totals or confirmed independent replication.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What is the actual scope of independent replication or separate safety materials\" and link them to original locations. No new search was conducted for independent trials, additional report or cohort lists, duplicate events or external safety or regulatory materials.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C02, C10, E07, H07.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Relationship records specifying repeated citation, shared populations or separate populations when separate materials are actually supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "The preserved evidence or citation list contains 1 EVOLVE-1 report record; parent replication R1 and independence I0 are historical axes. The two sheets or repeated safety citations are not counted as separate replications.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. No new search was conducted for independent trials, additional report or cohort lists, duplicate events or external safety or regulatory materials. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "No new search was conducted for independent trials, additional report or cohort lists, duplicate events or external safety or regulatory materials.", "uncertainty": "No new search was conducted for independent trials, additional report or cohort lists, duplicate events or external safety or regulatory materials.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Reports, study families, COI, shared outcomes and contrary-material lists" }, { "item_id": "N41", "question_type": "Evidence condition", "question": "At what level are efficacy outcomes and descriptive harms described?", "needed": "Original efficacy and safety tables, definitions, denominators or times and interpretive scope", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: At what level are efficacy outcomes and descriptive harms described.", "application_exception": "Non-significant survival or positive DCR does not erase harms, and descriptive statistics alone do not create a new causal safety verdict.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"At what level are efficacy outcomes and descriptive harms described\" and link them to original locations. Current synthesis of event-specific comparative estimates, causal attribution and long-term or rare harms remains unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E10, H09, C08.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original reports separately specifying the different analysis levels for efficacy and harms", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Retain null OS, positive secondary DCR and descriptive harms as their respective original results. Parent safety Caution is historical and does not confirm safety or absence of all harms.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Current synthesis of event-specific comparative estimates, causal attribution and long-term or rare harms remains unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Current synthesis of event-specific comparative estimates, causal attribution and long-term or rare harms remains unverified.", "uncertainty": "Current synthesis of event-specific comparative estimates, causal attribution and long-term or rare harms remains unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original efficacy and safety tables, definitions, denominators or times and interpretive scope" }, { "item_id": "N42", "question_type": "Evidence condition", "question": "How are parent grade, score, false or empty axis values and Korean or English drafts preserved?", "needed": "Separate copies preserving subclaim and parent values, Korean or English drafts, axes and historical verdict", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: How are parent grade, score, false or empty axis values and Korean or English drafts preserved.", "application_exception": "The parent's 34 points, B0/C0 or cross-check-applied history are not inherited as subclaim scores or axes, new fulfillment or review completion.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"How are parent grade, score, false or empty axis values and Korean or English drafts preserved\" and link them to original locations. Original cross-checking, grades and axes were not automatically applied as current review completion or selected subclaim values.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C01, C09, E06.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Preserved records separating complete pre-change originals, events, versions and decisions when verdict corrections are actually supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Preserve parent D, 34, Caution and axes B/H/R1/I0/E0/B0/C0; coprimary split false, large hard-endpoint RCT true, no-human-study false, primary-failed-secondary-positive true and empty override reasons. Complete Korean and English drafts and historical synthesis or grade decisions are context.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Original cross-checking, grades and axes were not automatically applied as current review completion or selected subclaim values. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Original cross-checking, grades and axes were not automatically applied as current review completion or selected subclaim values.", "uncertainty": "Original cross-checking, grades and axes were not automatically applied as current review completion or selected subclaim values.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Separate copies preserving subclaim and parent values, Korean or English drafts, axes and historical verdict" }, { "item_id": "N43", "question_type": "Evidence condition", "question": "Do the cutoff date, corrections and empty values differ from current production dates?", "needed": "Distinguishing original cutoff, correction, retraction or search history from production events", "role": "Required", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Do the cutoff date, corrections and empty values differ from current production dates.", "application_exception": "Empty corrections are not certified as no current corrections, and the original verification date is not changed into the current review date.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Do the cutoff date, corrections and empty values differ from current production dates\" and link them to original locations. Original additional-cutoff and detailed-classification fields are absent; no new search, registration, correction or retraction comparison or external reading was performed.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C09, C03.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Update records distinguishing historical scope from current additional events when materials or corrections are actually supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "Preserve original cutoff 2026-08-26 and empty correction and deliberation values. Bibliography or registration-agreement descriptions in the original Korean and English drafts are historical, while the current writing time is a production event.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Original additional-cutoff and detailed-classification fields are absent; no new search, registration, correction or retraction comparison or external reading was performed. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Original additional-cutoff and detailed-classification fields are absent; no new search, registration, correction or retraction comparison or external reading was performed.", "uncertainty": "Original additional-cutoff and detailed-classification fields are absent; no new search, registration, correction or retraction comparison or external reading was performed.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Distinguishing original cutoff, correction, retraction or search history from production events" }, { "item_id": "N44", "question_type": "Evidence condition", "question": "Is the scope kept from extending to current applicability, products or treatment decisions?", "needed": "Appropriate direct materials for extended questions and applicability differences from the original trial", "role": "Supplementary; required for extending applicability", "role_reason": "This condition is needed to separately document the selected improved-overall-survival question: Is the scope kept from extending to current applicability, products or treatment decisions.", "application_exception": "No new medication or dosing instructions, substitution or discontinuation of sorafenib or other treatments, or anticancer-treatment choices are created.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Is the scope kept from extending to current applicability, products or treatment decisions\" and link them to original locations. Current clinical practice, product or regulatory status, individual suitability and direct superiority of other treatments were not verified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C09, E08, E09, H08, H09.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Research-gap updates distinguishing selected scope, outcomes and harms when additional materials are authorized and supplied", "current_reports": [ "R01" ], "existence": "Relevant preserved-summary descriptions; existence or acquisition of detailed original materials remains unverified", "acquired_read": "Summary read; external materials not read", "observation": "This sheet documents the specified existing claim and EVOLVE-1's historical comparison, outcomes and gaps. Other products or doses, current treatment lines and individual treatment choice are outside this production scope.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Current clinical practice, product or regulatory status, individual suitability and direct superiority of other treatments were not verified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Current clinical practice, product or regulatory status, individual suitability and direct superiority of other treatments were not verified.", "uncertainty": "Current clinical practice, product or regulatory status, individual suitability and direct superiority of other treatments were not verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Appropriate direct materials for extended questions and applicability differences from the original trial" } ], "reports": [ { "report_id": "R01", "title": "Zhu AX, Kudo M, Assenat E, et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA. 2014;312:57-67. PMID: 25058218.", "url": "https://pubmed.ncbi.nlm.nih.gov/25058218/", "report_type": "Original summary of the same randomized, double-blind, placebo-controlled phase 3 trial report", "existence": "Report slot in the specified review summary's evidence/citation lists", "acquired_read": "Summary read; external abstracts, full texts and registrations unread", "study_family": "F01", "independent_replication": false, "observed_result": "Preserve OS HR 1.05 (95% CI 0.86~1.27), P=.68. The original subclaim note and parent describe a null result for improved overall survival.", "source_evidence_date": "2026-08-26", "materials": [ { "material_type": "Stored summary", "public_status": "Preserved complete summary copy", "access_status": "Preserved summary copy acquired; summary read", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-06T18:13:24.969435+09:00", "qualification": "Parent Korean and English drafts, two existing questions, bibliography, registration and original values were read for production; this is not reading clinical original materials." }, { "material_type": "External abstract", "public_status": "External material unread; no access attempts", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "The original PubMed bibliographic URL was linked. Abstract reading, material acquisition and operation tests were not performed." }, { "material_type": "External full text", "public_status": "External material unread; no access attempts", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "The original bibliographic URL links identity; it does not certify a direct full-text acquisition or reading URL." }, { "material_type": "External registration", "public_status": "External material unread; no access attempts", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Preserve the registration-ID record and original agreement wording. No registration URL absent from the existing summary was constructed, and current registration was not read." }, { "material_type": "Required protocol", "public_status": "Not acquired; detailed existence unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Original details of OS definitions, DCR or progression criteria, assessment times, exposure and blinding are required. Lack of acquisition is not converted into confirmed non-registration or selective reporting." }, { "material_type": "Required analysis plan", "public_status": "Not acquired; detailed existence unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Original OS HR analysis, DCR intervals or tests, hierarchy, multiplicity and missing-data handling materials are required. No new CI or verdict is created." }, { "material_type": "Required result tables and safety material", "public_status": "Not acquired; detailed existence unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Original tables are required to distinguish allocation or full analysis from DCR assessment, OS censoring, safety or at-risk denominators and descriptive harms." }, { "material_type": "Required sponsorship and competing-interest materials", "public_status": "Not acquired; detailed existence unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Original sponsorship, design, collection, analysis, writing and submission-role descriptions are preserved; complete COI, contracts and original declarations remain unread." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/25058218/" } ] } ], "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, and distinguish variations in interventions.", "review_level": "Methodological principles stated in existing pilot materials and condition templates were referenced. The methodological text was not reviewed again in this work." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish studies from reports and link them; do not omit a study solely because results are unreported.", "review_level": "Methodological principles stated in existing pilot materials and condition templates were referenced. The methodological text was not reviewed again in this work." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Define the outcome and effect of interest, then examine randomization, deviations, missing data, measurement and selective reporting.", "review_level": "Methodological principles stated in existing pilot materials and condition templates were referenced. The methodological text was not reviewed again in this work." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Methodological principles stated in existing pilot materials and condition templates were referenced. The methodological text was not reviewed again in this work." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence rates.", "review_level": "Methodological principles stated in existing pilot materials and condition templates were referenced. The methodological text was not reviewed again in this work." } ], "status_dictionary": { "Met": "The original content has been reviewed as meeting the conditions. This status is not used in this preparation.", "Partly verified": "Some information in the stored summary was linked during preparation; clinical verification or review is not complete.", "Unverified": "Required direct values, definitions or materials have not been established within the current storage and reading scope. This does not mean zero effect, no papers or failed access.", "Review incomplete": "Review of existing content or actual review incomplete.", "Not reported": "Used only when original materials were actually read and the outcome was judged unreported. Not used for external materials unread in this work.", "Inaccessible": "Used only when an actual access attempt has a recorded failure. Not used for access that was not attempted in this work.", "Insufficient evidence for the conditions": "Indicates insufficient direct materials for the relevant scope or conditions; it is not a new grade.", "Not applicable": "Used when the reason it does not apply to the original question is stated.", "Conflicting data": "Retains the scope of conflicting statements in original materials; it is not an arbitrary reassessment." }, "study_overlap": { "state": "Unverified", "unique_trial_count": null, "unique_participant_count": null, "reason": "The overall-survival and disease-control sheets share the same EVOLVE-1, PMID25058218, NCT01035229 and 546 participants (362/184). OS, DCR, TTP and safety are separated as outcome units; no additional trials or new participants are added." }, "history": [ { "date": "2026-10-11", "kind": "Separation of public-facing pages and materials", "view_version": "1.0", "change": "A public view and materials were prepared from the existing 44 items. No new clinical search, verification-status change or scoring was performed." } ], "language": "en", "translation_date": "2026-10-11" }