{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v2938-s1", "verdict_number": "2938", "title": "Everolimus · advanced hepatocellular carcinoma after sorafenib · evidence check for increased disease control", "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": "Secondary disease control after the primary survival endpoint failed; definition, assessment times, denominators and CI details remain unverified", "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 increased-disease-control 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 increased disease control, with the question distinguished from its original verdict record. The parent overall-survival context is preserved in the complete copy; other subquestions 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 increased-disease-control 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 C. Its note states: 56.1% versus 45.1%, but a secondary endpoint after the primary survival endpoint failed. Subclaim score, status and axis fields are absent; parent grade D, 34 points and Caution safety status 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 definition and secondary hierarchy of disease control?", "needed": "DCR definition, response criteria, primary or secondary plans and result tables", "role": "Required", "role_reason": "This condition is needed to separately document the selected increased-disease-control question: What are the definition and secondary hierarchy of disease control.", "application_exception": "C is the selected subclaim's historical grade; it is not changed into parent D34 or a current clinical verdict.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What are the definition and secondary hierarchy of disease control\" and link them to original locations. Response or stable-disease components, imaging assessment criteria, duration conditions and definitions of comparable assessed populations 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 reports or appendices from the same trial specifying disease-control definitions and analysis scope", "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 increased disease control, grade C. Its note states 56.1% versus 45.1%, but a secondary endpoint after the primary survival endpoint failed.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Response or stable-disease components, imaging assessment criteria, duration conditions and definitions of comparable assessed populations remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Response or stable-disease components, imaging assessment criteria, duration conditions and definitions of comparable assessed populations remain unverified.", "uncertainty": "Response or stable-disease components, imaging assessment criteria, duration conditions and definitions of comparable assessed populations remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "DCR definition, response criteria, primary or secondary plans and result tables" }, { "item_id": "N22", "question_type": "Evidence condition", "question": "What original between-group values are 56.1% versus 45.1% and P=.01?", "needed": "Original DCR result tables, denominators, CI and testing or adjustment methods", "role": "Required", "role_reason": "This condition is needed to separately document the selected increased-disease-control question: What original between-group values are 56.1% versus 45.1% and P=.01.", "application_exception": "Do not back-calculate new responder counts, differences, OR/RR or CI from rounded proportions.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What original between-group values are 56.1% versus 45.1% and P=.01\" and link them to original locations. The summary does not contain CI for the estimate, analysis methods for the proportion difference, adjustments or multiplicity handling.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C06, C07, E05.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: The same DCR report jointly presenting proportions, effect intervals and plans", "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 for everolimus versus placebo was 56.1% versus 45.1% (P=.01). The existing counterpoint description of an 11%p difference is preserved as a value already in the preserved summary.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. The summary does not contain CI for the estimate, analysis methods for the proportion difference, adjustments or multiplicity handling. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "The summary does not contain CI for the estimate, analysis methods for the proportion difference, adjustments or multiplicity handling.", "uncertainty": "The summary does not contain CI for the estimate, analysis methods for the proportion difference, adjustments or multiplicity handling.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original DCR result tables, denominators, CI and testing or adjustment methods" }, { "item_id": "N23", "question_type": "Evidence condition", "question": "What are the DCR denominators and numbers of people with disease control?", "needed": "Original DCR sample and event tables, assessment flow and analysis-population definitions", "role": "Required", "role_reason": "This condition is needed to separately document the selected increased-disease-control question: What are the DCR denominators and numbers of people with disease control.", "application_exception": "OS denominators 362/184 are not transferred into verified DCR denominators, and responder counts are not calculated from proportions.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What are the DCR denominators and numbers of people with disease control\" and link them to original locations. Group-specific DCR denominators, numerators, completed imaging assessments, missing assessments and analysis-inclusion rules 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 result tables distinguishing randomized, analyzed, assessable and disease-control 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": "The overall randomized and analyzed denominator was 546 participants (362/184). These are the parent original sample records; DCR assessable or analysis denominators and participant counts are not separately given in the original summary.", "condition_status": "Unverified", "status_reason": "Direct details of this condition were not verified within the current preserved-summary and externally unread scope. Group-specific DCR denominators, numerators, completed imaging assessments, missing assessments and analysis-inclusion rules remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Group-specific DCR denominators, numerators, completed imaging assessments, missing assessments and analysis-inclusion rules remain unverified.", "uncertainty": "Group-specific DCR denominators, numerators, completed imaging assessments, missing assessments and analysis-inclusion rules remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original DCR sample and event tables, assessment flow and analysis-population definitions" }, { "item_id": "N24", "question_type": "Evidence condition", "question": "How are non-assessment, death, progression and stable disease handled in DCR?", "needed": "DCR analysis rules, response classification and missing-data or death-handling tables", "role": "Required", "role_reason": "This condition is needed to separately document the selected increased-disease-control question: How are non-assessment, death, progression and stable disease handled in DCR.", "application_exception": "Classification, missing-data handling and sensitivity analyses for non-assessment, early death, progression and incomplete imaging 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 non-assessment, death, progression and stable disease handled in DCR\" and link them to original locations. Classification, missing-data handling and sensitivity analyses for non-assessment, early death, progression and incomplete imaging remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E04, C07.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Materials specifying original DCR analyses for non-assessment, death or discontinuation", "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": "DCR is a proportion outcome, while overall survival is a time-to-death outcome. The original record that everyone was included in the full analysis population does not mean that every DCR imaging or response status was known.", "condition_status": "Unverified", "status_reason": "Direct details of this condition were not verified within the current preserved-summary and externally unread scope. Classification, missing-data handling and sensitivity analyses for non-assessment, early death, progression and incomplete imaging remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Classification, missing-data handling and sensitivity analyses for non-assessment, early death, progression and incomplete imaging remain unverified.", "uncertainty": "Classification, missing-data handling and sensitivity analyses for non-assessment, early death, progression and incomplete imaging remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "DCR analysis rules, response classification and missing-data or death-handling tables" }, { "item_id": "N25", "question_type": "Evidence condition", "question": "What are the DCR assessment times and minimum duration?", "needed": "DCR definition, assessment schedule, minimum duration and data-cutoff date", "role": "Required", "role_reason": "This condition is needed to separately document the selected increased-disease-control question: What are the DCR assessment times and minimum duration.", "application_exception": "Median OS of 7.6/7.3 months or TTP of 3.0/2.6 months are not used to fill DCR assessment periods.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What are the DCR assessment times and minimum duration\" and link them to original locations. Whether this was best overall response or a particular time point, minimum stable-disease duration, imaging intervals and data cutoff remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C06, E03, E08.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Materials from the same trial linking time-specific or duration-specific DCR to original analyses", "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 materials give disease control of 56.1% versus 45.1%, but do not separately state the assessment time or duration for that proportion.", "condition_status": "Unverified", "status_reason": "Direct details of this condition were not verified within the current preserved-summary and externally unread scope. Whether this was best overall response or a particular time point, minimum stable-disease duration, imaging intervals and data cutoff remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Whether this was best overall response or a particular time point, minimum stable-disease duration, imaging intervals and data cutoff remain unverified.", "uncertainty": "Whether this was best overall response or a particular time point, minimum stable-disease duration, imaging intervals and data cutoff remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "DCR definition, assessment schedule, minimum duration and data-cutoff date" }, { "item_id": "N26", "question_type": "Evidence condition", "question": "What is the scope of imaging interpretation, central or local assessment and assessor blinding?", "needed": "DCR imaging criteria, assessors, original interpretation methods and appendices", "role": "Required", "role_reason": "This condition is needed to separately document the selected increased-disease-control question: What is the scope of imaging interpretation, central or local assessment and assessor blinding.", "application_exception": "The original double-blind design does not automatically certify completed central imaging interpretation or absence of measurement bias.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What is the scope of imaging interpretation, central or local assessment and assessor blinding\" and link them to original locations. Tumor-assessment criteria, measurement error, central or local interpretation, assessor blinding and response confirmation remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E03.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Materials from the same trial reporting actual DCR measurement or interpretation procedures and their agreement or differences", "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 trial design was double-blind with matching placebo. Separate information is needed on who interpreted disease-control imaging and how.", "condition_status": "Unverified", "status_reason": "Direct details of this condition were not verified within the current preserved-summary and externally unread scope. Tumor-assessment criteria, measurement error, central or local interpretation, assessor blinding and response confirmation remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Tumor-assessment criteria, measurement error, central or local interpretation, assessor blinding and response confirmation remain unverified.", "uncertainty": "Tumor-assessment criteria, measurement error, central or local interpretation, assessor blinding and response confirmation remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "DCR imaging criteria, assessors, original interpretation methods and appendices" }, { "item_id": "N27", "question_type": "Evidence condition", "question": "What are DCR effect intervals, clinical importance and multiplicity?", "needed": "DCR effect intervals, SAP, primary or secondary testing order and importance criteria", "role": "Required", "role_reason": "This condition is needed to separately document the selected increased-disease-control question: What are DCR effect intervals, clinical importance and multiplicity.", "application_exception": "P=.01 alone does not establish every effect size, current confirmatory success or individual clinical benefit.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What are DCR effect intervals, clinical importance and multiplicity\" and link them to original locations. CI for the DCR effect, prespecified importance, hierarchical or multiplicity adjustment and confirmatory status remain unverified.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E05, E06.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Materials linking planned and reported DCR intervals and testing scope", "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 DCR values and P=.01 are original records of a secondary result. The hierarchy restriction of positivity after survival failure is preserved alongside them.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. CI for the DCR effect, prespecified importance, hierarchical or multiplicity adjustment and confirmatory status remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "CI for the DCR effect, prespecified importance, hierarchical or multiplicity adjustment and confirmatory status remain unverified.", "uncertainty": "CI for the DCR effect, prespecified importance, hierarchical or multiplicity adjustment and confirmatory status remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "DCR effect intervals, SAP, primary or secondary testing order and importance criteria" }, { "item_id": "N28", "question_type": "Evidence condition", "question": "Are positive DCR and the null primary overall-survival result distinguished?", "needed": "Definitions, denominators, estimates and plans for each endpoint and their same-trial relationship", "role": "Required", "role_reason": "This condition is needed to separately document the selected increased-disease-control question: Are positive DCR and the null primary overall-survival result distinguished.", "application_exception": "Positive DCR is not transferred into increased OS, and the null OS result does not justify deleting preserved DCR values.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Are positive DCR and the null primary overall-survival result distinguished\" and link them to original locations. External materials directly verifying differences in models, times or denominators between the two endpoints and the DCR-OS relationship remain unread.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions C08, E09.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Original same-trial result tables presenting DCR and OS together without merging them", "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": "In the same trial, median OS was 7.6 versus 7.3 months, with 303/362 (83.7%) versus 151/184 (82.1%) deaths; HR 1.05 (95% CI 0.86 to 1.27; P=.68). The parent verdict and overall-survival sheet preserve the failure to increase survival.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. External materials directly verifying differences in models, times or denominators between the two endpoints and the DCR-OS relationship remain unread. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "External materials directly verifying differences in models, times or denominators between the two endpoints and the DCR-OS relationship remain unread.", "uncertainty": "External materials directly verifying differences in models, times or denominators between the two endpoints and the DCR-OS relationship remain unread.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Definitions, denominators, estimates and plans for each endpoint and their same-trial relationship" }, { "item_id": "N29", "question_type": "Evidence condition", "question": "What are the units and directions of time to progression and DCR?", "needed": "TTP definition and original results, DCR definition and separation of the two analyses", "role": "Required", "role_reason": "This condition is needed to separately document the selected increased-disease-control question: What are the units and directions of time to progression and DCR.", "application_exception": "TTP is not converted into PFS, DCR duration or survival benefit, and no difference between medians is calculated.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"What are the units and directions of time to progression and DCR\" and link them to original locations. Progression assessment, censoring or death handling, denominators, P and links to DCR assessment times 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: The same report linking original tumor assessments to progression-time 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": "TTP was a separate result of 3.0 versus 2.6 months, HR 0.93 (95% CI 0.75 to 1.15). DCR proportions and TTP time or HR use different units and analyses.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. Progression assessment, censoring or death handling, denominators, P and links to DCR assessment times remain unverified. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "Progression assessment, censoring or death handling, denominators, P and links to DCR assessment times remain unverified.", "uncertainty": "Progression assessment, censoring or death handling, denominators, P and links to DCR assessment times remain unverified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "TTP definition and original results, DCR definition and separation of the two analyses" }, { "item_id": "N30", "question_type": "Evidence condition", "question": "Does disease control answer questions about patient symptoms, quality of life or long-term outcomes?", "needed": "Direct DCR and patient-centered outcome materials, times, denominators and original analyses", "role": "Required", "role_reason": "This condition is needed to separately document the selected increased-disease-control question: Does disease control answer questions about patient symptoms, quality of life or long-term outcomes.", "application_exception": "Survival success is not imposed as mandatory for DCR itself, but DCR is not automatically extended into other patient benefits.", "criterion": "Distinguish preserved values, direct scope and unverified matters relevant to \"Does disease control answer questions about patient symptoms, quality of life or long-term outcomes\" and link them to original locations. This summary does not contain patient-reported symptoms, quality of life, tumor-control duration, individual benefit or mediation or surrogate validation.", "basis": "Own question-specific conditions informed by the preserved summary's original locations and family definitions E09, E08.", "condition_origin": "Case-specific question conditions; review of the existing content incomplete", "proposed_research": "Proposal: Materials separately reporting tumor control and patient-centered outcomes in the same or an appropriate separate study", "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 central explanation states that a higher tumor-control proportion did not translate into longer life. The selected question concerns DCR itself; survival, symptoms and quality of life are separate.", "condition_status": "Partly verified", "status_reason": "Some information for this item exists in the preserved summary and has been linked. This summary does not contain patient-reported symptoms, quality of life, tumor-control duration, individual benefit or mediation or surrogate validation. Existing content review remains incomplete; this does not establish clinical-condition fulfillment, zero effect or absence of materials.", "missingness": "This summary does not contain patient-reported symptoms, quality of life, tumor-control duration, individual benefit or mediation or surrogate validation.", "uncertainty": "This summary does not contain patient-reported symptoms, quality of life, tumor-control duration, individual benefit or mediation or surrogate validation.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Direct DCR and patient-centered outcome materials, times, denominators and original analyses" }, { "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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control 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 increased-disease-control question: Do the cutoff date, corrections and empty values differ from current production dates.", "application_exception": "Empty correction history is 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 increased-disease-control 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": "Disease control for everolimus versus placebo was 56.1% versus 45.1% (P=.01). The existing counterpoint description of an 11%p difference is preserved as a value already in the preserved summary.", "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": "2026-10-06T18:13:24.986687+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" }