{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v2940-s0", "verdict_number": "2940", "title": "ESA anemia correction × locoregional tumor control during head-and-neck radiotherapy — evidence checklist", "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": "The selected question and complete preserved parent-verdict summary were read for production. External abstracts, full texts, registrations, protocols/SAPs, review inclusion tables, original FDA warning texts and the page for other-indication verdict 2925 remain unread; access was not attempted. Existing methodological-application records and the status dictionary were reused; content review at the time of production was 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": "Head-and-neck squamous-cell carcinoma radiotherapy; original DAHANCA inclusion of Hb below 14.0 g/dL; stage and detailed eligibility remain unverified", "intervention": "Original studies of ESA anemia correction during radiotherapy; individual trial conditions for darbepoetin, epoetin beta and epoetin alfa", "dose": "Historical weekly darbepoetin exposure in DAHANCA; actual amount, route, target and adherence remain unverified. This is not medication, anticancer, anemia-correction or radiotherapy guidance.", "comparator": "Original trial-specific controls: ENHANCE placebo, RTOG ESA added or not added, and radiotherapy alone in the review; specific concomitant treatments remain unverified", "endpoint": "Existing question of improved locoregional tumor control; original time to failure and five-year cumulative failure are lower-is-better and showed worsening. Survival and Hb are separate outcomes.", "duration": "Original DAHANCA five-year cumulative outcomes and interim stopping; RTOG three- and five-year outcomes and follow-up and review-version context; detailed individual and endpoint follow-up remain unverified", "excluded_extensions": [ "Converting Hb correction into improved tumor control or survival", "Reversing failure-rate or HR direction into benefit", "Adding RTOG follow-up or review participants as independent groups", "Identical effects or harms in other cancers, populations or Hb targets, kidney disease or preterm-infant indications", "Current FDA-approval certification or medication, radiotherapy, anemia-correction or anticancer-treatment instructions" ] }, "requirements": [ { "item_id": "N01", "question_type": "Evidence condition", "question": "Is the selected original question improved locoregional tumor control?", "needed": "Link selected and parent claims, disease, exposure and failure direction", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: Is the selected original question improved locoregional tumor control?", "application_exception": "Do not arbitrarily rename the improvement question as a harm question or create a new verdict or split.", "criterion": "Preserve both the original positive question and the actual direction of its original results.", "basis": "M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are our own design / M03 §3.2.4; our own extension boundary", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If the question actually changes, separately record its original wording and excluded scope.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The selected existing question is improved locoregional tumor control. The parent describes harm from ESA anemia correction during head-and-neck radiotherapy. The question's improvement direction is distinguished from the observed worsening.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. The final count of independent claims remains undetermined.", "missingness": "The final count of independent claims remains undetermined.", "uncertainty": "Do not arbitrarily rename the improvement question as a harm question or create a new verdict or split. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Link selected and parent claims, disease, exposure and failure direction" }, { "item_id": "N02", "question_type": "Evidence condition", "question": "Are the subclaim's grade F and note separate from parent F12 and axes?", "needed": "Locations of actual and absent subclaim fields and original parent values", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: Are the subclaim's grade F and note separate from parent F12 and axes?", "application_exception": "Do not uniformly assign D to subclaims or copy parent 12 points, RX, I1, E-, B2/C0 as distinct subclaim values.", "criterion": "Distinguish the actual subclaim grade F from the parent verdict's scope.", "basis": "M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are our own design / M04 §4.5, §4.6.3; current material-conversion limits reflect review scope and our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If subclaim fields are actually added, distinguish the original version from the new event.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "Selected grade F and the note that five-year failure worsened to 47% versus 34% are preserved. Subclaim score, status and axes are absent and not recorded. Parent F12, safety Warning and axes belong to the parent.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. The original materials contain no distinct subclaim score, status or axes.", "missingness": "The original materials contain no distinct subclaim score, status or axes.", "uncertainty": "Do not uniformly assign D to subclaims or copy parent 12 points, RX, I1, E-, B2/C0 as distinct subclaim values. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Locations of actual and absent subclaim fields and original parent values" }, { "item_id": "N03", "question_type": "Evidence condition", "question": "Do repeated refutation, design limitations and cross-checking constitute current review?", "needed": "Korean and English wording, axes, verdict, corrections and methodological statements", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: Do repeated refutation, design limitations and cross-checking constitute current review?", "application_exception": "Do not inherit RX, the true large-hard-endpoint RCT indication or historical independence and cross-checking as current review or independence certification.", "criterion": "Separate original history from incomplete current content review.", "basis": "M04 §4.5, §4.6.3; current material-conversion limits reflect review scope and our own design / M08 §8.1–8.2.3; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If new evidence is requested, separate the original version from the new update event.", "current_reports": [ "R01", "R02", "R03", "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original parent describes F12 based on repeated refutation across three ESA trials, DAHANCA harm, early stopping at a planned interim analysis and open-label design. RX, cross-checking, true/false indications and empty values are historical records.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. No current RoB2/GRADE assessment, clinical reassessment or methodological certification was performed.", "missingness": "No current RoB2/GRADE assessment, clinical reassessment or methodological certification was performed.", "uncertainty": "Do not inherit RX, the true large-hard-endpoint RCT indication or historical independence and cross-checking as current review or independence certification. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Korean and English wording, axes, verdict, corrections and methodological statements" }, { "item_id": "N04", "question_type": "Evidence condition", "question": "Which materials were actually read, and which external materials remain unread?", "needed": "Acquisition and reading scope for preserved summaries and each external material", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: Which materials were actually read, and which external materials remain unread?", "application_exception": "Do not convert the presence of a URL or a statement about original-paper roles into current full-text reading, link verification or failed access.", "criterion": "Keep summary reading and external unread status separate for each material.", "basis": "M04 §4.5–4.6 material-collection and selection principles; separation of access and reading and hyperlink rules are our own design / M04 §4.5, §4.6.3; current material-conversion limits reflect review scope and our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If material and reading records are supplied, record only the actual level.", "current_reports": [ "R01", "R02", "R03", "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The selection and complete preserved summary were read for production. External abstracts, full texts, registrations, plans, original FDA warnings and verdict 2925's page and links remain unread; access was not attempted.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. No search of current external contents, all recent literature or regulatory materials was performed.", "missingness": "No search of current external contents, all recent literature or regulatory materials was performed.", "uncertainty": "Do not convert the presence of a URL or a statement about original-paper roles into current full-text reading, link verification or failed access. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Acquisition and reading scope for preserved summaries and each external material" }, { "item_id": "N05", "question_type": "Evidence condition", "question": "How are trials, the review and initial and follow-up reports linked?", "needed": "Original bibliography, review inclusion, initial and long-term reports and participant relationships", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: How are trials, the review and initial and follow-up reports linked?", "application_exception": "Do not add the review, original trials, two RTOG PMIDs or 2925 as new independent trials or participants.", "criterion": "Distinguish preserved report groups from undetermined unique totals and other indications.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort and outcome linking is our own application / M04 §4.6.1–4.6.2, M15 §15.3.1; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original lists are supplied, link each report to the same, different or uncertain study family.", "current_reports": [ "R01", "R02", "R03", "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "DAHANCA 10, ENHANCE, the same-trial initial and long-term RTOG 99-03 report group and the five-RCT review are distinguished. The reference to 2925 concerns another indication and is not a report of this cancer trial.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Unique trial and participant totals and review inclusion and overlap were not directly verified.", "missingness": "Unique trial and participant totals and review inclusion and overlap were not directly verified.", "uncertainty": "Do not add the review, original trials, two RTOG PMIDs or 2925 as new independent trials or participants. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original bibliography, review inclusion, initial and long-term reports and participant relationships" }, { "item_id": "N06", "question_type": "Evidence condition", "question": "What were DAHANCA's population and Hb eligibility conditions?", "needed": "Stage, site, inclusion and exclusion, Hb, anemia cause and baseline risk", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: What were DAHANCA's population and Hb eligibility conditions?", "application_exception": "Do not reuse the Hb eligibility threshold as an effect for all severe-anemia or other-cancer populations.", "criterion": "Record original population and Hb eligibility along with gaps in detailed conditions.", "basis": "M03 §3.2.1; detailed population conditions are our own design / M03 §3.2.1–3.2.4; dose, persistence and effect-modification details are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original population tables are supplied, distinguish the actual population from gaps for other cancers and goals.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The setting is head-and-neck squamous-cell carcinoma radiotherapy. The original DAHANCA condition included patients with Hb below 14.0 g/dL. Detailed stage, exact age and site and baseline anemia cause are absent from the summary.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Detailed stage, site, age, anemia cause and baseline risk remain unverified.", "missingness": "Detailed stage, site, age, anemia cause and baseline risk remain unverified.", "uncertainty": "Do not reuse the Hb eligibility threshold as an effect for all severe-anemia or other-cancer populations. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Stage, site, inclusion and exclusion, Hb, anemia cause and baseline risk" }, { "item_id": "N07", "question_type": "Evidence condition", "question": "What were darbepoetin exposure, goals and hematologic response in the trial?", "needed": "Nominal and actual drug exposure, Hb target, changes and discontinuation", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: What were darbepoetin exposure, goals and hematologic response in the trial?", "application_exception": "Do not write the historical weekly exposure as medication, anemia-correction, anticancer or radiotherapy-selection instructions.", "criterion": "Distinguish historical drug conditions from gaps in direct exposure and targets.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and assessment adaptations are our own design / M03 §3.2.3, M08 §8.2.2–8.2.3; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original exposure records are supplied, record trial conditions and actual use and goals.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The historical DAHANCA condition used weekly darbepoetin during radiotherapy. Exact dose, formulation, route, Hb target and stopping rules are absent from the summary.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Dose, route, actual adherence, achieved Hb and discontinuation details remain unverified.", "missingness": "Dose, route, actual adherence, achieved Hb and discontinuation details remain unverified.", "uncertainty": "Do not write the historical weekly exposure as medication, anemia-correction, anticancer or radiotherapy-selection instructions. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Nominal and actual drug exposure, Hb target, changes and discontinuation" }, { "item_id": "N08", "question_type": "Evidence condition", "question": "What were control radiotherapy and shared or concurrent cancer treatments?", "needed": "Trial-specific controls, radiotherapy plans and shared or concomitant cancer and anemia treatment", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: What were control radiotherapy and shared or concurrent cancer treatments?", "application_exception": "Do not use the review's control label to certify that every trial had no concomitant treatment.", "criterion": "Separate original comparison wording from gaps in detailed conditions.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and assessment adaptations are our own design / M03 §3.2.3, M08 §8.2.2–8.2.3; our own application / M19 §19.2.2–19.2.4 design considerations; detailed confounding records are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original comparison materials are supplied, distinguish the added drug from shared and other treatments.", "current_reports": [ "R01", "R02", "R03", "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original comparison is radiotherapy with an ESA added versus control. The review describes radiotherapy plus EPO versus radiotherapy alone. Specific radiotherapy and other concomitant treatments in each trial are absent from the summary.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Concomitant treatment, radiotherapy conditions and their balance remain unverified for each trial.", "missingness": "Concomitant treatment, radiotherapy conditions and their balance remain unverified for each trial.", "uncertainty": "Do not use the review's control label to certify that every trial had no concomitant treatment. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Trial-specific controls, radiotherapy plans and shared or concomitant cancer and anemia treatment" }, { "item_id": "N09", "question_type": "Evidence condition", "question": "Are planned 600, randomized 522 and evaluable 513 different stages?", "needed": "Allocation and evaluation flow by arm, correspondence of 254/259 to arms, exclusions and missingness", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: Are planned 600, randomized 522 and evaluable 513 different stages?", "application_exception": "Do not subtract counts to calculate attrition counts or rates or use planned 600 as the actual analysis population.", "criterion": "Distinguish original stage-specific denominators from unverified flow.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design / M08 §8.2.2, M15 §15.3.1; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original flow diagrams are supplied, record stages and inclusion rules by arm.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "DAHANCA's planned 600, 522 randomized at stopping and 513 evaluable (254/259) are separately preserved. Planning, allocation and evaluation represent different denominators.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Reasons for differences between allocation and evaluation, original arm correspondence and endpoint-denominator details remain externally unread.", "missingness": "Reasons for differences between allocation and evaluation, original arm correspondence and endpoint-denominator details remain externally unread.", "uncertainty": "Do not subtract counts to calculate attrition counts or rates or use planned 600 as the actual analysis population. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Allocation and evaluation flow by arm, correspondence of 254/259 to arms, exclusions and missingness" }, { "item_id": "N10", "question_type": "Evidence condition", "question": "What are the locoregional-failure time, five-year values and HR?", "needed": "Failure definition, timepoint and time, denominator, HR model and interval", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: What are the locoregional-failure time, five-year values and HR?", "application_exception": "Do not calculate new risk differences, CIs or P values from original proportions or HRs.", "criterion": "Attribute the original endpoint, 47/34%, HR and 95% CI to the relevant comparison.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design / M15 §15.3.1–15.3.3; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original results and methods are supplied, link cumulative values to the time-to-event estimate.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The primary endpoint was time to locoregional failure. Original worsening results were five-year cumulative failure of 47% with darbepoetin versus 34% in controls, HR 1.53 (95% CI 1.16–2.02).", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Failure components and definition, population at risk, censoring and model remain unverified.", "missingness": "Failure components and definition, population at risk, censoring and model remain unverified.", "uncertainty": "Do not calculate new risk differences, CIs or P values from original proportions or HRs. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Failure definition, timepoint and time, denominator, HR model and interval" }, { "item_id": "N11", "question_type": "Evidence condition", "question": "How should lower-is-better failure and the improvement question be read?", "needed": "Endpoint direction and relationship between question and result", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: How should lower-is-better failure and the improvement question be read?", "application_exception": "Do not turn increased failure into improved tumor control or a positive benefit.", "criterion": "Clearly distinguish the original improvement question from the observed worsening direction.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is our own design / M03 §3.2.4; our own extension boundary", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original definitions are added, record actual directions and interpretations of other endpoints.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original reader answer explicitly states that lower locoregional failure is better. Failure of 47% versus 34% is originally described as worsening, rather than improvement.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Detailed endpoint-specific success and failure adjudication rules remain unverified.", "missingness": "Detailed endpoint-specific success and failure adjudication rules remain unverified.", "uncertainty": "Do not turn increased failure into improved tumor control or a positive benefit. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Endpoint direction and relationship between question and result" }, { "item_id": "N12", "question_type": "Evidence condition", "question": "Are the five-year cumulative proportion and time-to-failure HR the same measure?", "needed": "Cumulative estimation, censoring, HR estimand, time and competing events", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: Are the five-year cumulative proportion and time-to-failure HR the same measure?", "application_exception": "Do not convert 47/34 or the HR into a new risk ratio, effect size or individual probability.", "criterion": "Distinguish different original measures and gaps in their models.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M08 §8.2.2, M15 §15.3.1; our own application / M15 §15.3.1–15.3.3; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original statistical methods are supplied, distinguish definitions of cumulative estimation and hazard comparisons.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "Five-year cumulative locoregional failure and the time-to-failure HR are separate expressions. The original HR is not converted into a simple five-year risk ratio or difference in cumulative percentages.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Cumulative estimation, proportional hazards, competing risks and adjustment remain unverified.", "missingness": "Cumulative estimation, proportional hazards, competing risks and adjustment remain unverified.", "uncertainty": "Do not convert 47/34 or the HR into a new risk ratio, effect size or individual probability. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Cumulative estimation, censoring, HR estimand, time and competing events" }, { "item_id": "N13", "question_type": "Evidence condition", "question": "What are the actual analysis and risk denominators for locoregional outcomes?", "needed": "Endpoint-specific analysis and risk populations, events and people, censoring and missingness", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: What are the actual analysis and risk denominators for locoregional outcomes?", "application_exception": "Do not copy evaluable 513 into every timepoint, survival or safety denominator or back-calculate event counts.", "criterion": "Record the original evaluation size and gaps in direct outcome denominators.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design / M08 §8.2.2, M15 §15.3.1; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original risk tables or flow diagrams are supplied, distinguish evaluation from timepoint and endpoint denominators.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original evaluable 513 (254/259) and five-year failure percentages are preserved. The five-year population at risk, follow-up, censoring and actual analysis denominators for each endpoint are absent from the summary.", "condition_status": "Unverified", "status_reason": "Required direct details are absent from the preserved summary and remain unverified. External materials remain unread. Five-year risk population, event counts and endpoint-specific analyses and censoring remain unverified.", "missingness": "Five-year risk population, event counts and endpoint-specific analyses and censoring remain unverified.", "uncertainty": "Do not copy evaluable 513 into every timepoint, survival or safety denominator or back-calculate event counts. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Endpoint-specific analysis and risk populations, events and people, censoring and missingness" }, { "item_id": "N14", "question_type": "Evidence condition", "question": "What was the actual scope of open-label design and central blinded review?", "needed": "Failure diagnosis and adjudication, imaging and clinical pathways and blinding by role", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: What was the actual scope of open-label design and central blinded review?", "application_exception": "Do not expand the absence of uniform central blinded review into an absence of all adjudication or examinations.", "criterion": "Separate original open-label and review limitations from direct details.", "basis": "M08 Table 8.2.a, M03 §3.2.4; our own application / M08 §8.1–8.2.3; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original adjudication methods are supplied, record actual pathways and limitations by role.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original DAHANCA account describes open-label design and says locoregional failure was not uniformly adjudicated through central blinded imaging review for every patient.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Patient-specific adjudication pathways, partial central review and assessor and analyst roles remain unverified.", "missingness": "Patient-specific adjudication pathways, partial central review and assessor and analyst roles remain unverified.", "uncertainty": "Do not expand the absence of uniform central blinded review into an absence of all adjudication or examinations. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Failure diagnosis and adjudication, imaging and clinical pathways and blinding by role" }, { "item_id": "N15", "question_type": "Evidence condition", "question": "What is known about randomization, allocation concealment and baseline balance?", "needed": "Allocation procedures, concealment, baseline and stratification factors and treatment balance", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: What is known about randomization, allocation concealment and baseline balance?", "application_exception": "Do not certify fulfillment of all methodological conditions from the randomized label, B2 or a past verdict.", "criterion": "Separate original design from gaps in direct procedures.", "basis": "M08 §8.1–8.2.3; our own application / M03 §3.2.1; detailed population conditions are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original methods and baseline data are supplied, distinguish design labels from actual procedures.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original summary describes DAHANCA as a multicenter randomized phase 3 trial. Actual tables or methods for sequence generation, concealment, stratification, baseline and cancer-treatment balance are absent.", "condition_status": "Unverified", "status_reason": "Required direct details are absent from the preserved summary and remain unverified. External materials remain unread. Direct methods for allocation, concealment and baseline balance remain unverified.", "missingness": "Direct methods for allocation, concealment and baseline balance remain unverified.", "uncertainty": "Do not certify fulfillment of all methodological conditions from the randomized label, B2 or a past verdict. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Allocation procedures, concealment, baseline and stratification factors and treatment balance" }, { "item_id": "N16", "question_type": "Evidence condition", "question": "What does early stopping at the planned interim analysis preserve?", "needed": "Interim timing and thresholds, committee, alpha, stopping and subsequent follow-up", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: What does early stopping at the planned interim analysis preserve?", "application_exception": "Do not turn the original planned-analysis wording into direct certification of advance planning or an exact bias magnitude.", "criterion": "Preserve the original stopping event and direct gaps in planning and follow-up.", "basis": "M08 Table 8.2.a, M04 §4.6.3; our own application / M08 §8.2.2, M15 §15.3.1; our own application / M15 §15.3.1–15.3.3; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original plans and stopping records are supplied, record prior rules and actual stopping and follow-up.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original trial account states that inferiority of the experimental arm at a planned interim analysis led to stopping at 522, before the planned 600.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Interim thresholds, boundaries, multiplicity, committee and subsequent follow-up details remain unverified.", "missingness": "Interim thresholds, boundaries, multiplicity, committee and subsequent follow-up details remain unverified.", "uncertainty": "Do not turn the original planned-analysis wording into direct certification of advance planning or an exact bias magnitude. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Interim timing and thresholds, committee, alpha, stopping and subsequent follow-up" }, { "item_id": "N17", "question_type": "Evidence condition", "question": "Does hematologic correction constitute a tumor-control benefit?", "needed": "Hematologic response, achieved Hb, denominator, tumor oxygenation and direct events", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: Does hematologic correction constitute a tumor-control benefit?", "application_exception": "Do not treat increased Hb as a guarantee of oxygenation, tumor-control or survival improvement.", "criterion": "Preserve original hematologic statements separately from direct clinical worsening.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M03 §3.2.4; our own extension boundary", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original response data are supplied, record Hb measures and clinical outcomes separately.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original crux states that anemia measures improved but cancer control and survival worsened. Actual Hb changes, responders and target attainment are absent from the summary.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Quantitative Hb response, tumor oxygenation and mediation analyses remain unverified.", "missingness": "Quantitative Hb response, tumor oxygenation and mediation analyses remain unverified.", "uncertainty": "Do not treat increased Hb as a guarantee of oxygenation, tumor-control or survival improvement. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Hematologic response, achieved Hb, denominator, tumor oxygenation and direct events" }, { "item_id": "N18", "question_type": "Evidence condition", "question": "What is the original event-free-survival value?", "needed": "EFS definition and components, denominator, HR model and interval confidence level", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What is the original event-free-survival value?", "application_exception": "Do not automatically copy locoregional-failure values or its 95% CI designation into EFS.", "criterion": "Keep the original EFS HR, interval and direction separate.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is our own design / M03 §3.2.4; our own extension boundary", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original results and methods are supplied, link EFS components and estimand to that value.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "DAHANCA event-free survival HR 1.36 (1.09–1.69) is described in the original harmful direction. This is a different outcome from the locoregional-failure HR.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. EFS components, model, denominator and detailed interval confidence level remain unverified.", "missingness": "EFS components, model, denominator and detailed interval confidence level remain unverified.", "uncertainty": "Do not automatically copy locoregional-failure values or its 95% CI designation into EFS. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "EFS definition and components, denominator, HR model and interval confidence level" }, { "item_id": "N19", "question_type": "Evidence condition", "question": "What is the disease-specific-death result?", "needed": "Cause-of-death adjudication, events and time, denominator, model and interval", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What is the disease-specific-death result?", "application_exception": "Do not fill disease-specific death with another endpoint's HR or 95% designation.", "criterion": "Separate the original disease-specific HR from gaps in direct definitions.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is our own design / M03 §3.2.4; our own extension boundary", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original mortality outcomes are supplied, record causes, denominators and estimates separately.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "DAHANCA disease-specific-death HR 1.43 (1.08–1.90) points in the original harmful direction. It is separate from overall death and failure.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Cause-of-death adjudication, events, risk population and detailed interval confidence level remain unverified.", "missingness": "Cause-of-death adjudication, events, risk population and detailed interval confidence level remain unverified.", "uncertainty": "Do not fill disease-specific death with another endpoint's HR or 95% designation. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Cause-of-death adjudication, events and time, denominator, model and interval" }, { "item_id": "N20", "question_type": "Evidence condition", "question": "What is the original overall-death HR?", "needed": "Overall death, risk population and denominator, time, model and interval", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What is the original overall-death HR?", "application_exception": "Do not calculate death counts, absolute-risk differences or new intervals from the original HR.", "criterion": "Preserve original overall-death values and gaps.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is our own design / M03 §3.2.4; our own extension boundary", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original mortality tables are supplied, record the actual overall-death estimate, time and denominator.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "DAHANCA overall-death HR 1.30 (1.02–1.64) is described in the original harmful direction. It is not mixed with numbers from other survival or failure outcomes.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Original overall-death count, risk population and detailed interval confidence level remain unverified.", "missingness": "Original overall-death count, risk population and detailed interval confidence level remain unverified.", "uncertainty": "Do not calculate death counts, absolute-risk differences or new intervals from the original HR. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Overall death, risk population and denominator, time, model and interval" }, { "item_id": "N21", "question_type": "Evidence condition", "question": "Is the sibling survival-improvement question separate from the main tumor question?", "needed": "Existing sibling question, endpoint definitions and denominators and original-result links", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: Is the sibling survival-improvement question separate from the main tumor question?", "application_exception": "Do not count the sibling row as a new trial or participant group or copy failure values into survival outcomes.", "criterion": "Distinguish original survival context from the selected question.", "basis": "M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are our own design / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M03 §3.2.4; our own extension boundary", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If the original question changes, separately record each existing question and its links.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The sibling survival question is improved survival, grade F, with a note about harmful disease-specific and overall death. It is preserved as context and remains separate from the selected locoregional question.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. This record also contains no distinct score, status or axes for the sibling.", "missingness": "This record also contains no distinct score, status or axes for the sibling.", "uncertainty": "Do not count the sibling row as a new trial or participant group or copy failure values into survival outcomes. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Existing sibling question, endpoint definitions and denominators and original-result links" }, { "item_id": "N22", "question_type": "Evidence condition", "question": "What are the details of follow-up, treatment deviations, missingness and censoring?", "needed": "Endpoint-specific flow, follow-up and censoring, treatment deviations and missing-data handling", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: What are the details of follow-up, treatment deviations, missingness and censoring?", "application_exception": "Do not calculate or infer new attrition or analysis rules from differences in allocation and evaluation counts.", "criterion": "Record direct gaps in original flow and time.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design / M08 §8.2.2, M15 §15.3.1; our own application / M19 §19.1.2–19.2.4, M04 §4.6.3; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original flow and analyses are supplied, distinguish allocation, evaluation, risk populations and losses.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "Evaluable 513, five-year cumulative results and early stopping are preserved. Individual follow-up, treatment deviation or crossover, exclusions, censoring and ITT/PP details are absent from the summary.", "condition_status": "Unverified", "status_reason": "Required direct details are absent from the preserved summary and remain unverified. External materials remain unread. Individual follow-up and deviations, ITT/PP and censoring and missing-data handling details remain unverified.", "missingness": "Individual follow-up and deviations, ITT/PP and censoring and missing-data handling details remain unverified.", "uncertainty": "Do not calculate or infer new attrition or analysis rules from differences in allocation and evaluation counts. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Endpoint-specific flow, follow-up and censoring, treatment deviations and missing-data handling" }, { "item_id": "N23", "question_type": "Evidence condition", "question": "What history underlies the original registration-absence statements?", "needed": "Original registration, timing, contemporaneous records and plans and changes", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: What history underlies the original registration-absence statements?", "application_exception": "Do not turn the historical absence wording into current certification of exhaustive registry absence or a new identifier.", "criterion": "Distinguish original values from the current unqueried scope.", "basis": "M04 §4.5–4.6 material-collection and selection principles; separation of access and reading and hyperlink rules are our own design / M04 §4.5, §4.6.3; current material-conversion limits reflect review scope and our own design / M08 Table 8.2.a, M04 §4.6.3; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original registration and planning materials are supplied, distinguish actual existence and contents from original history.", "current_reports": [ "R01", "R02", "R03", "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original DAHANCA and ENHANCE registration values say absent because they predate registration requirements; RTOG records NCT00004917, and the review says not applicable. These original expressions are preserved; external registration existence was not currently verified.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. External registration existence and prior plans remain unread.", "missingness": "External registration existence and prior plans remain unread.", "uncertainty": "Do not turn the historical absence wording into current certification of exhaustive registry absence or a new identifier. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original registration, timing, contemporaneous records and plans and changes" }, { "item_id": "N24", "question_type": "Evidence condition", "question": "Were prior endpoints, interim plans and the hierarchy of multiple outcomes read?", "needed": "Original plans, prior hierarchy, interim and final testing and changes", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: Were prior endpoints, interim plans and the hierarchy of multiple outcomes read?", "application_exception": "Do not certify every prior definition solely from the original primary-endpoint or planned-analysis labels.", "criterion": "Separate original roles from gaps in planning details.", "basis": "M08 Table 8.2.a, M04 §4.6.3; our own application / M04 §4.5–4.6 material-collection and selection principles; separation of access and reading and hyperlink rules are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original plans are supplied, distinguish contemporaneous roles from reports and follow-up.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original account includes primary failure, a planned interim analysis and major survival outcomes. Protocols, SAPs, all secondary and exploratory hierarchies, multiplicity and changes remain unread.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Direct documents for prior hierarchies, testing and changes remain unverified.", "missingness": "Direct documents for prior hierarchies, testing and changes remain unverified.", "uncertainty": "Do not certify every prior definition solely from the original primary-endpoint or planned-analysis labels. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original plans, prior hierarchy, interim and final testing and changes" }, { "item_id": "N25", "question_type": "Evidence condition", "question": "What are the clinical thresholds, individual effects and subgroups?", "needed": "Prior importance thresholds and subgroup hypotheses, interactions, denominators and intervals", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What are the clinical thresholds, individual effects and subgroups?", "application_exception": "Do not copy original effects into every stage, Hb target, dose or individual outcome.", "criterion": "Record overall original results and gaps in subgroup effects and clinical importance.", "basis": "M15 §15.3.1–15.3.3; our own application / M03 §3.2.1–3.2.4; dose, persistence and effect-modification details are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original plans or subgroup data are supplied, distinguish overall estimates from separate conditions.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "Original failure and HR intervals and harmful-survival statements are available. Clinical-success thresholds, individual-response criteria and Hb, stage or population interactions are absent from the summary.", "condition_status": "Unverified", "status_reason": "Required direct details are absent from the preserved summary and remain unverified. External materials remain unread. Prior clinical thresholds and direct subgroup effects and denominators remain unverified.", "missingness": "Prior clinical thresholds and direct subgroup effects and denominators remain unverified.", "uncertainty": "Do not copy original effects into every stage, Hb target, dose or individual outcome. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Prior importance thresholds and subgroup hypotheses, interactions, denominators and intervals" }, { "item_id": "N26", "question_type": "Evidence condition", "question": "What are ENHANCE's original population, design and RR results?", "needed": "PFS and survival definitions, adjusted model, actual denominators, ITT and intervals", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What are ENHANCE's original population, design and RR results?", "application_exception": "Do not change original RRs into DAHANCA HRs or probabilities of improvement.", "criterion": "Preserve each original RR, interval and P value and trial-specific denominator and hierarchy.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design / M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is our own design / M08 §8.1–8.2.3; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original ENHANCE methods and tables are supplied, record RR notation, estimand and endpoint-specific analyses.", "current_reports": [ "R02" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original ENHANCE notation is 351 patients (epoetin beta 180, placebo 171), ITT. Primary locoregional progression-free survival adjusted RR 1.62 (95% CI 1.22–2.14), P=.0008, and survival RR 1.39 (1.05–1.84) point in the original harmful direction.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Adjustment variables, actual endpoints and ITT handling and detailed survival-interval confidence level remain unverified.", "missingness": "Adjustment variables, actual endpoints and ITT handling and detailed survival-interval confidence level remain unverified.", "uncertainty": "Do not change original RRs into DAHANCA HRs or probabilities of improvement. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "PFS and survival definitions, adjusted model, actual denominators, ITT and intervals" }, { "item_id": "N27", "question_type": "Evidence condition", "question": "How do epoetin beta, epoetin alfa and darbepoetin exposures differ?", "needed": "Drug-specific formulation, amount and targets, shared and different treatments and populations", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: How do epoetin beta, epoetin alfa and darbepoetin exposures differ?", "application_exception": "Do not fill different drugs or targets with the same dose or conditions or extend them to every other indication.", "criterion": "Record shared claim context together with actual drug and exposure differences.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and assessment adaptations are our own design / M03 §3.2.3, M08 §8.2.2–8.2.3; our own application / M03 §3.2.1–3.2.4; dose, persistence and effect-modification details are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original intervention data are supplied, record drugs, targets and trial-specific conditions separately.", "current_reports": [ "R01", "R02", "R03" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original verdict concerns three ESAs in the same head-and-neck radiotherapy setting, rather than one drug alone. Trial-specific doses, Hb targets, actual exposures and combinations are not detailed in the summary.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Direct details of trial-specific targets, exposures, combinations and actual Hb remain unverified.", "missingness": "Direct details of trial-specific targets, exposures, combinations and actual Hb remain unverified.", "uncertainty": "Do not fill different drugs or targets with the same dose or conditions or extend them to every other indication. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Drug-specific formulation, amount and targets, shared and different treatments and populations" }, { "item_id": "N28", "question_type": "Evidence condition", "question": "What are RTOG's initial and long-term endpoint values?", "needed": "Timepoint-specific failure and OS, denominators, estimates, CIs and analysis plans", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What are RTOG's initial and long-term endpoint values?", "application_exception": "Do not turn nonsignificance into zero effect, equivalence or guaranteed individual survival.", "criterion": "Keep original timepoints, proportions and P values attached to their respective endpoints.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is our own design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original RTOG tables are supplied, link each timepoint and endpoint to its original intervals and denominators.", "current_reports": [ "R03" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "RTOG's 148 patients are described as showing no epoetin alfa benefit. Three-year failure 44% versus 36% (P=.56), five-year failure 46.2% versus 39.4% (P=.42) and OS 36.9% versus 38.2% (P=.54) are separately preserved.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Actual analysis denominators, original CIs and models and detailed OS timepoint definitions remain unverified.", "missingness": "Actual analysis denominators, original CIs and models and detailed OS timepoint definitions remain unverified.", "uncertainty": "Do not turn nonsignificance into zero effect, equivalence or guaranteed individual survival. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Timepoint-specific failure and OS, denominators, estimates, CIs and analysis plans" }, { "item_id": "N29", "question_type": "Evidence condition", "question": "Do the two RTOG PMIDs refer to reports of the same trial?", "needed": "Initial and follow-up populations, timepoints and analysis and report relationships", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: Do the two RTOG PMIDs refer to reports of the same trial?", "application_exception": "Do not add two PMIDs or timepoints as two groups of 148 participants or independent replications.", "criterion": "Preserve the original report group, bibliography and same-population relationship.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort and outcome linking is our own application / M04 §4.6.1–4.6.2, M15 §15.3.1; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original reports are supplied, distinguish same-cohort follow-up from separate trials.", "current_reports": [ "R03" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The RTOG citation preserves initial PMID 17716826 and long-term PMID 25670542 together. Its original flag groups reports of the same trial as one. The URL identifies the long-term report's bibliography.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Actual follow-up and denominators of the follow-up report and each original full text remain unread.", "missingness": "Actual follow-up and denominators of the follow-up report and each original full text remain unread.", "uncertainty": "Do not add two PMIDs or timepoints as two groups of 148 participants or independent replications. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Initial and follow-up populations, timepoints and analysis and report relationships" }, { "item_id": "N30", "question_type": "Evidence condition", "question": "Can the five-RCT, 1,397-participant review be added to original trials?", "needed": "Inclusion and contribution lists, trial identities, populations and timepoints and overlap", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: Can the five-RCT, 1,397-participant review be added to original trials?", "application_exception": "Do not add review 1,397 and individual trials or follow-up to create new participant or trial totals.", "criterion": "Distinguish original review counts from undetermined unique totals.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort and outcome linking is our own application / M04 §4.6.1–4.6.2, M15 §15.3.1; our own application / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original inclusion tables are supplied, link the review to unique original study families.", "current_reports": [ "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original review size is five RCTs and 1,397 participants. Report and included-trial lists and overlap with current original trials and follow-up were not directly read.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Review inclusion, contributions and unique trial and participant totals remain undetermined.", "missingness": "Review inclusion, contributions and unique trial and participant totals remain undetermined.", "uncertainty": "Do not add review 1,397 and individual trials or follow-up to create new participant or trial totals. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Inclusion and contribution lists, trial identities, populations and timepoints and overlap" }, { "item_id": "N31", "question_type": "Evidence condition", "question": "What is the event direction of the review's ORs?", "needed": "Review event and success coding, models and endpoint-specific contributions and intervals", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What is the event direction of the review's ORs?", "application_exception": "Do not reverse OR<1 into reduced death or failure with ESA or convert it into an HR or RR.", "criterion": "Preserve the original review direction, measures and intervals at their stated level.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is our own design / M15 §15.3.1–15.3.3; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original review tables are supplied, record OR coding, estimands and contributions.", "current_reports": [ "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "OS Peto OR 0.73 (95% CI 0.58–0.91) and locoregional PFS OR 0.63 (0.49–0.80) are originally described as worse with radiotherapy plus EPO and favoring radiotherapy alone.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. OR coding, synthesis model and detailed PFS-interval confidence level remain unverified.", "missingness": "OR coding, synthesis model and detailed PFS-interval confidence level remain unverified.", "uncertainty": "Do not reverse OR<1 into reduced death or failure with ESA or convert it into an HR or RR. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Review event and success coding, models and endpoint-specific contributions and intervals" }, { "item_id": "N32", "question_type": "Evidence condition", "question": "What are the review's timing, subsets, heterogeneity and direct comparisons?", "needed": "Review version, inclusion timing, endpoint subsets, synthesis, heterogeneity and conditions", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What are the review's timing, subsets, heterogeneity and direct comparisons?", "application_exception": "Do not assume every recent report was included in the review or arbitrarily correct years or identities.", "criterion": "Preserve original dates and bibliography and gaps in actual inclusion.", "basis": "M04 §4.6.1–4.6.2, M15 §15.3.1; our own application / M08 §8.2.2, M15 §15.3.1; our own application / M03 §3.2.1–3.2.4; dose, persistence and effect-modification details are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original review tables are supplied, record versions and actual included families and conditions.", "current_reports": [ "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The review's original bibliography is from 2009, whereas the original DAHANCA report is from 2018. Actual inclusion and updates, contributions by drug, target and timepoint, heterogeneity and subgroup analyses are absent from the summary.", "condition_status": "Unverified", "status_reason": "Required direct details are absent from the preserved summary and remain unverified. External materials remain unread. Temporal relationships between versions and inclusion, subsets and quantitative heterogeneity remain unverified.", "missingness": "Temporal relationships between versions and inclusion, subsets and quantitative heterogeneity remain unverified.", "uncertainty": "Do not assume every recent report was included in the review or arbitrarily correct years or identities. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Review version, inclusion timing, endpoint subsets, synthesis, heterogeneity and conditions" }, { "item_id": "N33", "question_type": "Evidence condition", "question": "Are repeated refutation in the same indication and other goals distinguished?", "needed": "Direct questions, exposures and endpoints for each indication and goal", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: Are repeated refutation in the same indication and other goals distinguished?", "application_exception": "Do not merge 2925 as tumor-control benefit, safety evidence or a separate anticancer trial here.", "criterion": "Preserve only the original link context for another goal and do not create treatment-selection instructions.", "basis": "M03 §3.2.1; detailed population conditions are our own design / M03 §3.2.2–3.2.3; reverse-direction labeling and assessment adaptations are our own design / M03 §3.2.4; our own extension boundary", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If materials for another requested question are supplied, record its original unit and population separately.", "current_reports": [ "R01", "R02", "R03", "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original scope is limited to improved tumor control during cancer radiotherapy. Kidney-disease anemia and transfusion reduction in very-low-birth-weight preterm infants, verdict 2925 B72, concern different populations and goals.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Pages and original materials for other indications remain unread.", "missingness": "Pages and original materials for other indications remain unread.", "uncertainty": "Do not merge 2925 as tumor-control benefit, safety evidence or a separate anticancer trial here. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Direct questions, exposures and endpoints for each indication and goal" }, { "item_id": "N34", "question_type": "Harm information", "question": "What is the original statement of no differences in ancillary safety?", "needed": "Safety definitions and collection, individual events and denominators, estimates and intervals", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What is the original statement of no differences in ancillary safety?", "application_exception": "Do not turn unverified differences into zero events, equivalence of all safety outcomes or harmlessness.", "criterion": "Preserve both original ancillary-safety statements and direct clinical worsening.", "basis": "M19 §19.1.2–19.2.4; detailed distinctions are our own design / M19 §19.2.2–19.2.4, M03 §3.2.3; our own application / M19 §19.1.2–19.2.4; our own application / M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original safety tables are supplied, record original observations and intervals for each item.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original counterview says no excess serious adverse events, cardiovascular increase or differences in acute or late radiation toxicity were identified. Quantitative events, denominators, CIs and P values are absent from the summary.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Direct safety event counts, intervals and collection methods remain unverified.", "missingness": "Direct safety event counts, intervals and collection methods remain unverified.", "uncertainty": "Do not turn unverified differences into zero events, equivalence of all safety outcomes or harmlessness. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Safety definitions and collection, individual events and denominators, estimates and intervals" }, { "item_id": "N35", "question_type": "Harm information", "question": "Are major tumor and survival harms separate from safety collection?", "needed": "Clinical-harm and safety endpoints, collection and adjudication, severity and discontinuation", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: Are major tumor and survival harms separate from safety collection?", "application_exception": "Do not erase demonstrated tumor or survival harm based on no differences in ancillary safety.", "criterion": "Distinguish endpoint-specific harm from gaps in complete collection.", "basis": "M19 §19.1.2–19.2.4; detailed distinctions are our own design / CHAMGAP's own interpretation boundary. M19 principles are referenced; no official causality tool was run / M19 §19.1.2–19.2.4; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original safety and endpoint data are supplied, distinguish actual clinical outcomes from separate collection.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original explanation states that demonstrated harm came from primary and major tumor-control and survival endpoints, rather than ancillary safety items. A complete list of all adverse events is absent from the summary.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Complete harm definitions, collection, discontinuation and severity tables remain unverified.", "missingness": "Complete harm definitions, collection, discontinuation and severity tables remain unverified.", "uncertainty": "Do not erase demonstrated tumor or survival harm based on no differences in ancillary safety. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Clinical-harm and safety endpoints, collection and adjudication, severity and discontinuation" }, { "item_id": "N36", "question_type": "Harm information", "question": "What are harm-event, participant and time denominators and timepoints?", "needed": "Safety-specific denominators and durations, event timing and treatment and follow-up discontinuation", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What are harm-event, participant and time denominators and timepoints?", "application_exception": "Do not copy 513/522 or five-year figures as actual denominators or duration for every harm.", "criterion": "Separate original clinical context from gaps in safety time and denominators.", "basis": "M19 §19.2 design-specific harm questions; temporal-relationship details are our own design / M19 §19.1.2–19.2.4; our own application / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original safety flow is supplied, record efficacy evaluation separately from safety exposure and time.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "Original context includes evaluable 513, five-year tumor outcomes and interim stopping. Numbers and time at risk for each safety event, onset, recovery, exposure and discontinuation timing are absent.", "condition_status": "Unverified", "status_reason": "Required direct details are absent from the preserved summary and remain unverified. External materials remain unread. Denominators, time, discontinuation and recovery for each safety event remain unverified.", "missingness": "Denominators, time, discontinuation and recovery for each safety event remain unverified.", "uncertainty": "Do not copy 513/522 or five-year figures as actual denominators or duration for every harm. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Safety-specific denominators and durations, event timing and treatment and follow-up discontinuation" }, { "item_id": "N37", "question_type": "Harm information", "question": "What is known about baseline cancer risk, concurrent treatments and alternative attribution?", "needed": "Baseline and concurrent exposures, event attribution, adjustment and alternative explanations", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What is known about baseline cancer risk, concurrent treatments and alternative attribution?", "application_exception": "Do not turn population-level harmful direction into established causes or mechanisms for individual patients.", "criterion": "Separate original comparisons from gaps in attribution and mechanisms.", "basis": "M19 §19.2.2–19.2.4 design considerations; detailed confounding records are our own design / M03 §3.2.3, M08 §8.2.2–8.2.3; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original methods and event data are supplied, distinguish randomized comparisons from individual causes and mechanisms.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "Radiotherapy and ESA comparisons and clinical worsening are original-summary observations. Actual event-specific details of baseline and concurrent treatments, disease characteristics, other exposures and adjustment are absent.", "condition_status": "Unverified", "status_reason": "Required direct details are absent from the preserved summary and remain unverified. External materials remain unread. Individual-event alternatives, mechanisms, concurrent treatments and adjustment details remain unverified.", "missingness": "Individual-event alternatives, mechanisms, concurrent treatments and adjustment details remain unverified.", "uncertainty": "Do not turn population-level harmful direction into established causes or mechanisms for individual patients. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Baseline and concurrent exposures, event attribution, adjustment and alternative explanations" }, { "item_id": "N38", "question_type": "Harm information", "question": "What is known about missing and complete safety and clinical follow-up?", "needed": "Safety and clinical flow, losses and omissions, reporting and censoring and sensitivity", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What is known about missing and complete safety and clinical follow-up?", "application_exception": "Do not turn allocation and evaluation differences into absence of safety events or an exact bias magnitude.", "criterion": "Record original outcome limitations in follow-up and reporting.", "basis": "M19 §19.1.2–19.2.4, M04 §4.6.3; our own application / M08 §8.2.2, M15 §15.3.1; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original flow and surveillance records are supplied, distinguish observed outcomes from uncaptured and missing data.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "Original history includes evaluation and allocation, early stopping and open-label design. Safety surveillance, follow-up losses, omissions, censoring and completeness of all event reporting are absent from the summary.", "condition_status": "Unverified", "status_reason": "Required direct details are absent from the preserved summary and remain unverified. External materials remain unread. Safety follow-up, omissions and overall reporting completeness remain unverified.", "missingness": "Safety follow-up, omissions and overall reporting completeness remain unverified.", "uncertainty": "Do not turn allocation and evaluation differences into absence of safety events or an exact bias magnitude. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Safety and clinical flow, losses and omissions, reporting and censoring and sensitivity" }, { "item_id": "N39", "question_type": "Harm information", "question": "What is the scope of FDA warnings, original harm, current verification and causality?", "needed": "Original regulatory text and versions, indications and clinical-outcome and judgment scope", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What is the scope of FDA warnings, original harm, current verification and causality?", "application_exception": "Do not create new regulatory links, certify current approval or provide treatment, medication, radiotherapy-selection or dosing instructions.", "criterion": "Separate original warnings and clinical harm from the current unqueried regulatory scope.", "basis": "CHAMGAP's own interpretation boundary. M19 principles are referenced; no official causality tool was run / M04 §4.5–4.6 material-collection and selection principles; separation of access and reading and hyperlink rules are our own design / M04 §4.5, §4.6.3; current material-conversion limits reflect review scope and our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original regulatory materials are supplied, distinguish historical statements from direct contents and current updates.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "Original advertising interpretation and safety explanation preserve the FDA boxed warning about shortened cancer survival and tumor progression or recurrence. The preserved summary contains no regulatory-original URL or separate citation. Current approvals and warning contents were not queried.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Official warning and approval texts, latest versions and direct mechanistic verification remain unread.", "missingness": "Official warning and approval texts, latest versions and direct mechanistic verification remain unread.", "uncertainty": "Do not create new regulatory links, certify current approval or provide treatment, medication, radiotherapy-selection or dosing instructions. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original regulatory text and versions, indications and clinical-outcome and judgment scope" }, { "item_id": "N40", "question_type": "Harm information", "question": "Does this answer questions about other cancers, Hb targets, populations or long-term and rare harms?", "needed": "Direct population-, target- and exposure-specific materials and safety follow-up", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: Does this answer questions about other cancers, Hb targets, populations or long-term and rare harms?", "application_exception": "Do not extend original repeated refutation to identical harm for every ESA indication and exposure.", "criterion": "Record original limits and gaps in safety and effect extensions.", "basis": "M19 §19.1.2–19.2.4; our own application / M03 §3.2.1–3.2.4; dose, persistence and effect-modification details are our own design / M03 §3.2.1; detailed population conditions are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If direct materials are supplied, distinguish the selected claim from other indication and harm questions.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original verdict concerns tumor control during head-and-neck radiotherapy. Direct results for other cancers, populations, Hb targets, other ESA exposures or rare and other long-term harms are absent from this summary.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Direct evidence for other populations, goals and rare harms remains unverified.", "missingness": "Direct evidence for other populations, goals and rare harms remains unverified.", "uncertainty": "Do not extend original repeated refutation to identical harm for every ESA indication and exposure. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Direct population-, target- and exposure-specific materials and safety follow-up" }, { "item_id": "N41", "question_type": "Evidence condition", "question": "What were DAHANCA's mixed support, device or drug supply and roles?", "needed": "Original sponsorship and supply, roles, contracts and data access and COI declarations", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: What were DAHANCA's mixed support, device or drug supply and roles?", "application_exception": "Do not remove free-drug/GCP-cost or noninvolvement statements or upgrade I1 to current independence certification.", "criterion": "Separate original support, supply and role context from currently unread declarations.", "basis": "CHAMGAP's own independence and attribution conditions. Official methodological sections used in this pilot do not guarantee every detail of this item / M04 §4.6.1–4.6.2, M15 §15.3.1; our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original declarations are supplied, distinguish support and supply from each actual operational role.", "current_reports": [ "R01" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "Danish Cancer Society and Amgen support, Amgen's free trial drug/Aranesp and main GCP and quality-control costs are preserved. The original account says the trial was investigator driven, Amgen had no design, conduct, collection or analysis role and offered no comments despite a manuscript-comment opportunity.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Original contracts, complete declarations and direct current role comparisons remain unread.", "missingness": "Original contracts, complete declarations and direct current role comparisons remain unread.", "uncertainty": "Do not remove free-drug/GCP-cost or noninvolvement statements or upgrade I1 to current independence certification. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original sponsorship and supply, roles, contracts and data access and COI declarations" }, { "item_id": "N42", "question_type": "Evidence condition", "question": "What are funding and author relationships in other trials and the review?", "needed": "Report-specific sponsorship and supply, author, analysis and manuscript roles and review declarations", "role": "Supplementary", "role_reason": "This condition is needed to record original information and gaps separately for the question: What are funding and author relationships in other trials and the review?", "application_exception": "Do not certify current investigator or population independence solely from different supporting institutions.", "criterion": "Preserve report-specific original funding and relationship gaps.", "basis": "CHAMGAP's own independence and attribution conditions. Official methodological sections used in this pilot do not guarantee every detail of this item / M04 §4.6.1–4.6.2 distinction between studies and reports; cohort and outcome linking is our own application", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original declarations and inclusion tables are supplied, record roles, families and funding by report.", "current_reports": [ "R02", "R03", "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "Original accounts record F. Hoffmann-La Roche support for ENHANCE, NCI/Ortho Biotech support for RTOG and mixed public and company funding of the review's included trials. Detailed company and investigator roles and the review's own declarations are absent.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Detailed roles, the review's own funding and COIs and investigator and population overlap remain unverified.", "missingness": "Detailed roles, the review's own funding and COIs and investigator and population overlap remain unverified.", "uncertainty": "Do not certify current investigator or population independence solely from different supporting institutions. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Report-specific sponsorship and supply, author, analysis and manuscript roles and review declarations" }, { "item_id": "N43", "question_type": "Evidence condition", "question": "Are original repeated refutation and unique trial and repeated-harm counts established?", "needed": "Unique families, inclusion and follow-up, investigators and funding and event and population lists", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: Are original repeated refutation and unique trial and repeated-harm counts established?", "application_exception": "Do not add review, follow-up, the same population or endpoints as new independent trials or repeated events.", "criterion": "Distinguish original history from unrecorded, undetermined unique counts.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort and outcome linking is our own application / M04 §4.6.1–4.6.2, M15 §15.3.1; our own application / M04 §4.6.1–4.6.2; harm-material adaptations are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If original lists are supplied, link same, different and uncertain families and repeated citations.", "current_reports": [ "R01", "R02", "R03", "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "The original parent describes repeated refutation/RX across three different drugs and independent trials. This is preserved, but review inclusion, trial identities, replications and follow-up were not exhaustively compared, so unique counts and independence are not certified.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Unique trial totals, participant and event sums and independent repeated-harm counts remain undetermined.", "missingness": "Unique trial totals, participant and event sums and independent repeated-harm counts remain undetermined.", "uncertainty": "Do not add review, follow-up, the same population or endpoints as new independent trials or repeated events. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Unique families, inclusion and follow-up, investigators and funding and event and population lists" }, { "item_id": "N44", "question_type": "Evidence condition", "question": "Are original dates, corrections, Korean and English texts and empty values preserved?", "needed": "Original dates, corrections and languages and current input and update scope", "role": "Required", "role_reason": "This condition is needed to record original information and gaps separately for the question: Are original dates, corrections, Korean and English texts and empty values preserved?", "application_exception": "Do not borrow historical dates or cross-checking as current clinical-verification dates or certify exhaustive absence from empty corrections.", "criterion": "Record original history together with current production and incomplete content review.", "basis": "M04 §4.5, §4.6.3; current material-conversion limits reflect review scope and our own design / M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are our own design", "condition_origin": "Production based on original materials; existing content review remains incomplete", "proposed_research": "Proposal: If actual update materials are supplied, distinguish the complete original version from the correction event.", "current_reports": [ "R01", "R02", "R03", "R04" ], "existence": "Original preserved-summary and bibliography links; existence and content of necessary external details remain unverified", "acquired_read": "Summary read; external materials not read", "observation": "Date 2026-08-26, empty corrections and deliberation, Korean and English texts and parent-axis true, false, unrecorded and empty-string values are preserved.", "condition_status": "Partly verified", "status_reason": "Original preserved-summary statements were linked for production as partly verified; clinical verification and content review are not complete. Separate evidence-cutoff and facet fields are absent; no latest correction, retraction or regulatory search was performed.", "missingness": "Separate evidence-cutoff and facet fields are absent; no latest correction, retraction or regulatory search was performed.", "uncertainty": "Do not borrow historical dates or cross-checking as current clinical-verification dates or certify exhaustive absence from empty corrections. Existing content review remains incomplete and external original materials were not directly verified.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original dates, corrections and languages and current input and update scope" } ], "reports": [ { "report_id": "R01", "title": "Overgaard J, Hoff CM, Hansen HS, et al. DAHANCA 10—Effect of darbepoetin alfa and radiotherapy in squamous cell carcinoma of the head and neck. Radiother Oncol. 2018;127:12-19. PMID: 29523409.", "url": "https://pubmed.ncbi.nlm.nih.gov/29523409/", "report_type": "DAHANCA 10 report of an open-label phase 3 darbepoetin-radiotherapy trial", "existence": "Report groups linked from original preserved evidence and citation lists", "acquired_read": "Summary read; external abstracts and full texts not read", "study_family": "F01", "independent_replication": false, "observed_result": "522 randomized/513 evaluable (254/259). Five-year cumulative failure 47% versus 34%, HR 1.53 (95% CI 1.16–2.02); EFS HR 1.36 (1.09–1.69), disease-specific death 1.43 (1.08–1.90) and overall death 1.30 (1.02–1.64) point in the original harmful direction. Original history records interim stopping at 522 of planned 600.", "source_evidence_date": "2026-08-26", "materials": [ { "material_type": "Stored summary", "public_status": "Local preserved copy", "access_status": "Local preserved summary acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-06T17:56:26.880575+09:00", "qualification": "Relevant evidence, bibliography and Korean and English context from the complete specified preserved summary were linked for production. External full texts were not read." }, { "material_type": "External abstract", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Only original bibliography links were preserved; current access, reading and link verification were not performed." }, { "material_type": "External full text or follow-up report", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Original links connect bibliographic identities and do not indicate direct full-text acquisition or reading. Follow-up of the same trial is not a new independent population." }, { "material_type": "External registration", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "The original registration statement that it predates registration requirements and is absent was preserved; current registration existence or absence was not directly queried or certified." }, { "material_type": "Required materials: protocol or review plan", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Required scope: failure and survival definitions, flow and censoring, interim plans and adjudication, exposure and targets, safety and Amgen roles; original-material existence, public availability and acquisition remain unverified." }, { "material_type": "Required materials: SAP, interim or synthesis analyses", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Endpoint hierarchy and models, interim analysis, censoring and missingness, or review coding, inclusion and synthesis methods remain unread." }, { "material_type": "Required materials: results, denominators, safety and regulation", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Direct original endpoint- and timepoint-specific results, flow, safety and relevant regulatory materials are needed; FDA links or contents were not newly queried or created." }, { "material_type": "Required materials: funding and COI", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Report-specific sponsorship, free drug, operational, analysis and manuscript roles and review declarations were not directly read." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/29523409/" } ] }, { "report_id": "R02", "title": "Henke M, Laszig R, Rübe C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy. Lancet. 2003;362:1255-1260. PMID: 14575968.", "url": "https://pubmed.ncbi.nlm.nih.gov/14575968/", "report_type": "ENHANCE epoetin-beta double-blind placebo-controlled report", "existence": "Report groups linked from original preserved evidence and citation lists", "acquired_read": "Summary read; external abstracts and full texts not read", "study_family": "F02", "independent_replication": false, "observed_result": "Original notation: 351 (180/171), ITT. Locoregional PFS adjusted RR 1.62 (95% CI 1.22–2.14), P=.0008; survival RR 1.39 (1.05–1.84), in the original harmful direction. Details of models, exposure and intervals remain unread.", "source_evidence_date": "2026-08-26", "materials": [ { "material_type": "Stored summary", "public_status": "Local preserved copy", "access_status": "Local preserved summary acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-06T17:56:26.880575+09:00", "qualification": "Relevant evidence, bibliography and Korean and English context from the complete specified preserved summary were linked for production. External full texts were not read." }, { "material_type": "External abstract", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Only original bibliography links were preserved; current access, reading and link verification were not performed." }, { "material_type": "External full text or follow-up report", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Original links connect bibliographic identities and do not indicate direct full-text acquisition or reading. Follow-up of the same trial is not a new independent population." }, { "material_type": "External registration", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "The original registration statement that it predates registration requirements and is absent was preserved; current registration existence or absence was not directly queried or certified." }, { "material_type": "Required materials: protocol or review plan", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Required scope: PFS and survival definitions, actual denominators and ITT, adjustment, exposure and targets, safety and Roche roles; original-material existence, public availability and acquisition remain unverified." }, { "material_type": "Required materials: SAP, interim or synthesis analyses", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Endpoint hierarchy and models, interim analysis, censoring and missingness, or review coding, inclusion and synthesis methods remain unread." }, { "material_type": "Required materials: results, denominators, safety and regulation", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Direct original endpoint- and timepoint-specific results, flow, safety and relevant regulatory materials are needed; FDA links or contents were not newly queried or created." }, { "material_type": "Required materials: funding and COI", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Report-specific sponsorship, free drug, operational, analysis and manuscript roles and review declarations were not directly read." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/14575968/" } ] }, { "report_id": "R03", "title": "Machtay M, Pajak TF, Suntharalingam M, et al. Radiotherapy with or without erythropoietin for anemic patients with head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2007. PMID: 17716826; long-term follow-up PMID: 25670542.", "url": "https://pubmed.ncbi.nlm.nih.gov/25670542/", "report_type": "Preserved RTOG 99-03 initial and long-term report group from the same trial", "existence": "Report groups linked from original preserved evidence and citation lists", "acquired_read": "Summary read; external abstracts and full texts not read", "study_family": "F03", "independent_replication": false, "observed_result": "148 randomized. Three-year failure 44% versus 36% (P=.56), five-year failure 46.2% versus 39.4% (P=.42), OS 36.9% versus 38.2% (P=.54), originally described as no benefit. Initial PMID 17716826 and long-term PMID 25670542 concern the same trial and are not added as new populations.", "source_evidence_date": "2026-08-26", "materials": [ { "material_type": "Stored summary", "public_status": "Local preserved copy", "access_status": "Local preserved summary acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-06T17:56:26.880575+09:00", "qualification": "Relevant evidence, bibliography and Korean and English context from the complete specified preserved summary were linked for production. External full texts were not read." }, { "material_type": "External abstract", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Only original bibliography links were preserved; current access, reading and link verification were not performed." }, { "material_type": "External full text or follow-up report", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Original links connect bibliographic identities and do not indicate direct full-text acquisition or reading. Follow-up of the same trial is not a new independent population." }, { "material_type": "External registration", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Only original string NCT00004917 was preserved; registration contents, timing and plans remain unread." }, { "material_type": "Required materials: protocol or review plan", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Required scope: initial and follow-up flow, endpoint- and duration-specific denominators and CIs, exposure and analyses and NCI/Ortho roles; original-material existence, public availability and acquisition remain unverified." }, { "material_type": "Required materials: SAP, interim or synthesis analyses", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Endpoint hierarchy and models, interim analysis, censoring and missingness, or review coding, inclusion and synthesis methods remain unread." }, { "material_type": "Required materials: results, denominators, safety and regulation", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Direct original endpoint- and timepoint-specific results, flow, safety and relevant regulatory materials are needed; FDA links or contents were not newly queried or created." }, { "material_type": "Required materials: funding and COI", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Report-specific sponsorship, free drug, operational, analysis and manuscript roles and review declarations were not directly read." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/25670542/" } ] }, { "report_id": "R04", "title": "Bohlius J, Schmidlin K, Brillant C, et al. Erythropoietin or darbepoetin for patients with cancer. Cochrane review subgroup of head and neck radiotherapy trials. PMID: 19588382.", "url": "https://pubmed.ncbi.nlm.nih.gov/19588382/", "report_type": "Systematic-review and meta-analysis report of five RCTs in head-and-neck radiotherapy", "existence": "Report groups linked from original preserved evidence and citation lists", "acquired_read": "Summary read; external abstracts and full texts not read", "study_family": "F04", "independent_replication": false, "observed_result": "Original review size: five RCTs/1,397 participants. OS Peto OR 0.73 (95% CI 0.58–0.91), locoregional PFS OR 0.63 (0.49–0.80), originally favoring radiotherapy alone. Inclusion, contributions, timing and independent-population counts remain unverified.", "source_evidence_date": "2026-08-26", "materials": [ { "material_type": "Stored summary", "public_status": "Local preserved copy", "access_status": "Local preserved summary acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-06T17:56:26.880575+09:00", "qualification": "Relevant evidence, bibliography and Korean and English context from the complete specified preserved summary were linked for production. External full texts were not read." }, { "material_type": "External abstract", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Only original bibliography links were preserved; current access, reading and link verification were not performed." }, { "material_type": "External full text or follow-up report", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Original links connect bibliographic identities and do not indicate direct full-text acquisition or reading. Follow-up of the same trial is not a new independent population." }, { "material_type": "External registration", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "The original registration value not applicable was preserved; current registration existence or absence was not directly queried or certified." }, { "material_type": "Required materials: protocol or review plan", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Required scope: version, inclusion and contributions, unique families, OR coding, synthesis, heterogeneity, sponsorship and COI; original-material existence, public availability and acquisition remain unverified." }, { "material_type": "Required materials: SAP, interim or synthesis analyses", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Endpoint hierarchy and models, interim analysis, censoring and missingness, or review coding, inclusion and synthesis methods remain unread." }, { "material_type": "Required materials: results, denominators, safety and regulation", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Direct original endpoint- and timepoint-specific results, flow, safety and relevant regulatory materials are needed; FDA links or contents were not newly queried or created." }, { "material_type": "Required materials: funding and COI", "public_status": "Current public availability and detailed existence remain unverified", "access_status": "Access not attempted; not obtained", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "Report-specific sponsorship, free drug, operational, analysis and manuscript roles and review declarations were not directly read." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/19588382/" } ] } ], "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": "DAHANCA's same population, failure, survival, Hb, safety, interim and follow-up context; original independence statements are historical and do not currently certify unique families. ENHANCE's original drug, population, locoregional PFS and survival context is not added to other trial values or denominators. The two initial and long-term RTOG 99-03 PMIDs form the original same-trial report group; 148 participants, durations and endpoints are not added as new independent populations. The five-RCT/1397-participant review's inclusion version, contributions and overlap remain unread and are not counted independently alongside original trials." }, "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" }