{
  "schema_version": "chamgap-public-evidence-check-1.0",
  "public_id": "v2939-s1",
  "verdict_number": "2939",
  "title": "PEGPH20 add-on therapy × increased objective response — evidence sheet for a lower-order endpoint under fixed-sequence testing",
  "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 complete existing review summary was read for production, linking existing URLs and identifiers. External abstracts, full texts, registration, protocols and SAP were not newly read or checked.",
    "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": "Previously untreated stage IV pancreatic ductal adenocarcinoma with stromal hyaluronan staining of at least 50%; detailed eligibility remains unread",
    "intervention": "Historical research conditions for PEGPH20 add-on therapy; distinguished from shared nab-paclitaxel, gemcitabine and mandatory enoxaparin prophylaxis",
    "dose": "Research-drug or prophylaxis doses, schedules and actual-exposure details remain unread; no treatment or medication instructions are created",
    "comparator": "Original comparison with matching placebo and the same shared anticancer treatment and mandatory prophylaxis",
    "endpoint": "Selected lower-order objective response; exploratory scope after OS failure distinguished from PFS and harms",
    "duration": "Original median OS of 11.2/11.5 months and PFS of 7.1/7.1 months are outcome values and are not used as intervention or follow-up duration; data-cutoff and actual-exposure or follow-up details remain unread",
    "excluded_extensions": [
      "Transferring ORR into OS, PFS or clinical-function benefit",
      "Certifying exploratory lower-order results as confirmatory success under fixed-sequence testing",
      "Certifying effects or harms in other cancers, treatment lines, combinations or prophylaxis conditions",
      "Adding different endpoints, sibling sheets or the same people as independent evidence",
      "Drug selection, use, prophylaxis, substitution or treatment recommendations"
    ]
  },
  "requirements": [
    {
      "item_id": "N01",
      "question_type": "Comparative efficacy",
      "question": "Are the original objective-response subclaim verdict and parent survival grade D distinguished?",
      "needed": "Separate records of subclaim original wording, grade, note and parent context",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Separate records of subclaim original wording, grade, note and parent context",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Link additional materials separately to the response question and parent survival results.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The selected existing claim is increased objective response, original grade C. Its note states 47% versus 36%, but no eligibility for confirmatory testing under the fixed sequence. The parent is OS D34 with Caution.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Absent subclaim scores, statuses and axes are not filled with parent values. Subclaim C is not uniformly changed to D, and no new grade is assessed.",
      "missingness": "Absent subclaim scores, statuses and axes are not filled with parent values. Subclaim C is not uniformly changed to D, and no new grade is assessed.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Absent subclaim scores, statuses and axes are not filled with parent values. Subclaim C is not uniformly changed to D, and no new grade is assessed."
    },
    {
      "item_id": "N02",
      "question_type": "Comparative efficacy",
      "question": "Who was actually eligible for response-rate analysis?",
      "needed": "Expression, cancer type, stage, treatment line, baseline conditions and denominators",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Expression, cancer type, stage, treatment line, baseline conditions and denominators",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original eligibility, baseline tumor, biomarker and assessable analysis-population materials.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The original population was untreated stage IV pancreatic ductal adenocarcinoma with stromal hyaluronan staining of at least 50%.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not automatically apply this to responses at other expression levels, cancers, treatment lines or stages. Additional response-analysis eligibility and assessable populations remain unread.",
      "missingness": "Do not automatically apply this to responses at other expression levels, cancers, treatment lines or stages. Additional response-analysis eligibility and assessable populations remain unread.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Do not automatically apply this to responses at other expression levels, cancers, treatment lines or stages. Additional response-analysis eligibility and assessable populations remain unread."
    },
    {
      "item_id": "N03",
      "question_type": "Comparative efficacy",
      "question": "Were added PEGPH20, matching placebo and shared anticancer treatment separated?",
      "needed": "Original drug, placebo, shared-treatment and actual-exposure records",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Original drug, placebo, shared-treatment and actual-exposure records",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original intervention, placebo, shared regimen and actual-exposure materials.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The trial context of nab-paclitaxel plus gemcitabine in both groups, with added PEGPH20 versus matching placebo, is preserved.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Original response effects are not converted into overall efficacy of shared anticancer treatment. Dose, schedule, actual exposure and discontinuation details remain unread; no treatment guidance is created.",
      "missingness": "Original response effects are not converted into overall efficacy of shared anticancer treatment. Dose, schedule, actual exposure and discontinuation details remain unread; no treatment guidance is created.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Original response effects are not converted into overall efficacy of shared anticancer treatment. Dose, schedule, actual exposure and discontinuation details remain unread; no treatment guidance is created."
    },
    {
      "item_id": "N04",
      "question_type": "Comparative efficacy",
      "question": "Are shared thrombosis-prophylaxis conditions and actual management scope retained?",
      "needed": "Prophylaxis, concomitant management, actual exposure, adherence and denominators",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Prophylaxis, concomitant management, actual exposure, adherence and denominators",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original shared-management, prophylactic-exposure, deviation and group-specific event materials.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "Both groups had mandatory enoxaparin prophylaxis because of thromboembolic risk.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Research conditions are not converted into prophylactic-medication instructions for readers. Response or safety results are not automatically applied to other conditions without prophylaxis.",
      "missingness": "Research conditions are not converted into prophylactic-medication instructions for readers. Response or safety results are not automatically applied to other conditions without prophylaxis.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Research conditions are not converted into prophylactic-medication instructions for readers. Response or safety results are not automatically applied to other conditions without prophylaxis."
    },
    {
      "item_id": "N05",
      "question_type": "Comparative efficacy",
      "question": "Are 494 randomized participants, 492 ITT participants and response-rate denominators the same?",
      "needed": "Group-specific allocation, ITT, assessable-imaging and response-analysis denominators",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Group-specific allocation, ITT, assessable-imaging and response-analysis denominators",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original group allocation, response-analysis populations, assessable counts and original responder tables.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "494 participants randomized 2:1 and 492 ITT participants are overall trial information.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. 492 is not certified as a response-analysis denominator that was not directly given. Group-specific denominators and responder counts are not back-calculated from proportions.",
      "missingness": "492 is not certified as a response-analysis denominator that was not directly given. Group-specific denominators and responder counts are not back-calculated from proportions.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "492 is not certified as a response-analysis denominator that was not directly given. Group-specific denominators and responder counts are not back-calculated from proportions."
    },
    {
      "item_id": "N06",
      "question_type": "Comparative efficacy",
      "question": "What were objective-response criteria, confirmation, times and assessors?",
      "needed": "Imaging criteria, response types, confirmatory assessments, times and measurement procedures",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Imaging criteria, response types, confirmatory assessments, times and measurement procedures",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original response definitions, assessment procedures, assessors, schedules and classification tables.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The preserved summary records objective imaging response as a separate lower-order outcome.",
      "condition_status": "Unverified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. RECIST version, central or institutional assessment, complete or partial response, confirmation schedules and classification methods are absent from the summary and are not created.",
      "missingness": "RECIST version, central or institutional assessment, complete or partial response, confirmation schedules and classification methods are absent from the summary and are not created.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "RECIST version, central or institutional assessment, complete or partial response, confirmation schedules and classification methods are absent from the summary and are not created."
    },
    {
      "item_id": "N07",
      "question_type": "Comparative efficacy",
      "question": "Were original proportions of 47% versus 36% and missing original responder counts retained?",
      "needed": "Original group-specific proportions, responders, denominators and aggregation rules",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Original group-specific proportions, responders, denominators and aggregation rules",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original responders, group-specific analysis denominators and aggregation rules.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "Objective response of 47% versus 36% is recorded in the original summary body.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not calculate new proportion differences, responder counts, NNT or RR. Group labels, original denominators and missing-assessment handling details remain unread.",
      "missingness": "Do not calculate new proportion differences, responder counts, NNT or RR. Group labels, original denominators and missing-assessment handling details remain unread.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Do not calculate new proportion differences, responder counts, NNT or RR. Group labels, original denominators and missing-assessment handling details remain unread."
    },
    {
      "item_id": "N08",
      "question_type": "Comparative efficacy",
      "question": "Are the response ratio 1.29, CI and new tests distinguished?",
      "needed": "Original ratio, CI, testing, model, denominator and effect definitions",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Original ratio, CI, testing, model, denominator and effect definitions",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original ratio definitions, models, intervals, denominators and testing plans.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The original response ratio is 1.29 (95% CI 1.03 to 1.63).",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not recalculate from 47/36 or create the ratio model, new P, exact tests, adjustment variables or inferential eligibility.",
      "missingness": "Do not recalculate from 47/36 or create the ratio model, new P, exact tests, adjustment variables or inferential eligibility.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Do not recalculate from 47/36 or create the ratio model, new P, exact tests, adjustment variables or inferential eligibility."
    },
    {
      "item_id": "N09",
      "question_type": "Comparative efficacy",
      "question": "Was the fixed sequence requiring significant survival first preserved?",
      "needed": "Original plans for testing sequence, alpha, endpoint hierarchy and changes",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Original plans for testing sequence, alpha, endpoint hierarchy and changes",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original SAP, fixed sequence, alpha, testing and outcome lists.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The preserved summary states that overall survival had to be significant first for lower-order confirmatory testing, and response must be interpreted as exploratory after survival failed.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Exclusion of 1 by the CI alone does not promote response into prespecified confirmatory success.",
      "missingness": "Exclusion of 1 by the CI alone does not promote response into prespecified confirmatory success.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Exclusion of 1 by the CI alone does not promote response into prespecified confirmatory success."
    },
    {
      "item_id": "N10",
      "question_type": "Comparative efficacy",
      "question": "Are the prespecified 2019 amendment, sole primary overall survival and response hierarchy distinguished?",
      "needed": "Registration, protocol, SAP, dates and decisions before and after amendment",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Registration, protocol, SAP, dates and decisions before and after amendment",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original registration history, amendment events, protocol and SAP separately.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The summary records OS as the sole primary endpoint after the prespecified 2019 amendment and states agreement with NCT02715804.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Response is not newly designated as coprimary. Earlier hierarchy, amendment circumstances and actual registration content remain unread.",
      "missingness": "Response is not newly designated as coprimary. Earlier hierarchy, amendment circumstances and actual registration content remain unread.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Response is not newly designated as coprimary. Earlier hierarchy, amendment circumstances and actual registration content remain unread."
    },
    {
      "item_id": "N11",
      "question_type": "Comparative efficacy",
      "question": "Were exploratory response signals, clinical importance and confirmatory effects separated?",
      "needed": "Response importance, prespecified success thresholds, hierarchy and original CI",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Response importance, prespecified success thresholds, hierarchy and original CI",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original planned importance, response maintenance, clinical links and hierarchy.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The preserved summary recognizes improved response itself while stating that it is not a confirmatory conclusion or equivalent to survival benefit.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not create clinical-importance thresholds, confirmatory response success or universal treatment benefit absent from the original summary.",
      "missingness": "Do not create clinical-importance thresholds, confirmatory response success or universal treatment benefit absent from the original summary.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Do not create clinical-importance thresholds, confirmatory response success or universal treatment benefit absent from the original summary."
    },
    {
      "item_id": "N12",
      "question_type": "Comparative efficacy",
      "question": "Were null overall survival and increased response preserved together?",
      "needed": "Original OS medians, HR, CI, P, events and denominators",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Original OS medians, HR, CI, P, events and denominators",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original OS models, curves, censoring, group-specific events and denominators separately.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "For 492 ITT participants, OS of 11.2 versus 11.5 months, HR 1.00 (95% CI 0.80 to 1.27), P=.97 and 330 deaths are preserved.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Imaging response is not transferred into prolonged OS. The original context that the OS CI retained possible benefit is also not erased.",
      "missingness": "Imaging response is not transferred into prolonged OS. The original context that the OS CI retained possible benefit is also not erased.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Imaging response is not transferred into prolonged OS. The original context that the OS CI retained possible benefit is also not erased."
    },
    {
      "item_id": "N13",
      "question_type": "Comparative efficacy",
      "question": "Are null progression-free survival, response duration and progression the same outcome?",
      "needed": "PFS, response duration, imaging-response definitions, effects and denominators",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "PFS, response duration, imaging-response definitions, effects and denominators",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original PFS, response-duration, persistence and progression definitions and tables.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "Median PFS of 7.1 versus 7.1 months, HR 0.97 (95% CI 0.75 to 1.26), is preserved.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Positive response is not converted into PFS or response-duration benefit. Response duration, progression times and PFS P remain unread.",
      "missingness": "Positive response is not converted into PFS or response-duration benefit. Response duration, progression times and PFS P remain unread.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Positive response is not converted into PFS or response-duration benefit. Response duration, progression times and PFS P remain unread."
    },
    {
      "item_id": "N14",
      "question_type": "Comparative efficacy",
      "question": "Were central allocation, double-blinding and imaging-assessment details separated?",
      "needed": "Original allocation-concealment, blinding, imaging-assessor and analyst methods",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Original allocation-concealment, blinding, imaging-assessor and analyst methods",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original allocation, imaging-assessment, blinding roles and unblinding procedures.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "Central interactive-response-system allocation and double-blinding with matching placebo appear in the preserved summary.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. This information alone does not constitute new verification of central imaging assessment, independent assessors or analyst blinding.",
      "missingness": "This information alone does not constitute new verification of central imaging assessment, independent assessors or analyst blinding.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "This information alone does not constitute new verification of central imaging assessment, independent assessors or analyst blinding."
    },
    {
      "item_id": "N15",
      "question_type": "Comparative efficacy",
      "question": "Were gaps in missing response assessments, deviations, progression, death handling and denominators retained?",
      "needed": "Missing imaging assessments, analysis populations, deaths, progression and missing-data rules",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Missing imaging assessments, analysis populations, deaths, progression and missing-data rules",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original assessable populations, reasons for missing assessments, death or progression handling, missing-data handling and sensitivity materials.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "Overall ITT information and original response proportions exist, but detailed response-assessment data flow is absent from the summary.",
      "condition_status": "Unverified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Proportions alone do not establish complete imaging for all patients, death or progression handling or ITT response rules.",
      "missingness": "Proportions alone do not establish complete imaging for all patients, death or progression handling or ITT response rules.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Proportions alone do not establish complete imaging for all patients, death or progression handling or ITT response rules."
    },
    {
      "item_id": "N16",
      "question_type": "Comparative efficacy",
      "question": "What gaps remain in response interpretation of actual exposure, anticancer intensity, discontinuation or subsequent treatment?",
      "needed": "Added drug, shared anticancer treatment, prophylaxis, crossover, discontinuation and actual exposure",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Added drug, shared anticancer treatment, prophylaxis, crossover, discontinuation and actual exposure",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original exposure, discontinuation, subsequent management and prespecified effect-of-interest materials.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "Historical intervention, shared anticancer treatment and mandatory prophylaxis conditions are preserved.",
      "condition_status": "Unverified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not newly calculate responder-specific exposure, dose intensity, discontinuation or subsequent-treatment effects absent from the original summary.",
      "missingness": "Do not newly calculate responder-specific exposure, dose intensity, discontinuation or subsequent-treatment effects absent from the original summary.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Do not newly calculate responder-specific exposure, dose intensity, discontinuation or subsequent-treatment effects absent from the original summary."
    },
    {
      "item_id": "N17",
      "question_type": "Comparative efficacy",
      "question": "Were response subgroups, expression analyses and multiple outcomes verified prospectively?",
      "needed": "Original plans for subgroups, interactions, hierarchy, denominators and testing",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Original plans for subgroups, interactions, hierarchy, denominators and testing",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original subgroup, biomarker, interaction, multiplicity and effect materials.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The selected population's staining threshold of at least 50% and lower-order response plans are preserved in the summary.",
      "condition_status": "Unverified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. No additional expression strata, treatment lines, subgroup response counts, P or independent success are created.",
      "missingness": "No additional expression strata, treatment lines, subgroup response counts, P or independent success are created.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "No additional expression strata, treatment lines, subgroup response counts, P or independent success are created."
    },
    {
      "item_id": "N18",
      "question_type": "Comparative efficacy",
      "question": "Were mechanisms and imaging shrinkage not converted into clinical function or survival benefit?",
      "needed": "Separate materials for response, mechanisms and direct clinical function or survival",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Separate materials for response, mechanisms and direct clinical function or survival",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain direct endpoints, effects and denominators separately for clinical-function, symptom and survival questions.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The preserved summary explicitly states that imaging response must not be promoted into survival benefit.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Mechanistic, pain, quality-of-life, independent-living or mortality benefits are not filled in from response rates. These direct values are absent from the summary.",
      "missingness": "Mechanistic, pain, quality-of-life, independent-living or mortality benefits are not filled in from response rates. These direct values are absent from the summary.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Mechanistic, pain, quality-of-life, independent-living or mortality benefits are not filled in from response rates. These direct values are absent from the summary."
    },
    {
      "item_id": "N19",
      "question_type": "Comparative efficacy",
      "question": "Were the same HALO report, cohort and two endpoints not added as independent evidence?",
      "needed": "Relationships among original trial, report, shared participants, times and sibling sheets",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Relationships among original trial, report, shared participants, times and sibling sheets",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Link new reports to existing trial and registration identifiers and relationships.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The two sheets share one HALO109-301 literature record, NCT02715804 and the 494/492-participant context.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Response, OS, PFS and sibling sheets are not added as new independent trials or participants. Final independent and total-participant counts remain unrecorded.",
      "missingness": "Response, OS, PFS and sibling sheets are not added as new independent trials or participants. Final independent and total-participant counts remain unrecorded.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Response, OS, PFS and sibling sheets are not added as new independent trials or participants. Final independent and total-participant counts remain unrecorded."
    },
    {
      "item_id": "N20",
      "question_type": "Comparative efficacy",
      "question": "Were Halozyme support, drug or placebo, 2 employees and Paragon writing separated?",
      "needed": "Cash support, products, affiliations, management and external analysis or writing roles",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Cash support, products, affiliations, management and external analysis or writing roles",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain each support, supply, affiliation, analysis, management and writing disclosure.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "Halozyme sponsorship and support, protocol, drug or placebo, data management, 2 company authors and Paragon medical writing paid by Halozyme are preserved.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Paragon writing is not converted into outsourced analysis. Employee identities, statistical-analysis and data-access role details remain unread.",
      "missingness": "Paragon writing is not converted into outsourced analysis. Employee identities, statistical-analysis and data-access role details remain unread.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Paragon writing is not converted into outsourced analysis. Employee identities, statistical-analysis and data-access role details remain unread."
    },
    {
      "item_id": "N21",
      "question_type": "Comparative efficacy",
      "question": "Were original R1 and I0 and unverified independent replication retained?",
      "needed": "Relationships among manufacturer trial, funding, investigators and original verdict",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Relationships among manufacturer trial, funding, investigators and original verdict",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Link study, funding, author and denominator relationships of additional materials separately.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "Parent R1 and I0 and the original wording that the confirmed efficacy trial was one manufacturer development trial are retained.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Positive response or two outcomes do not certify independent replication by other investigators or funding sources.",
      "missingness": "Positive response or two outcomes do not certify independent replication by other investigators or funding sources.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Positive response or two outcomes do not certify independent replication by other investigators or funding sources."
    },
    {
      "item_id": "N22",
      "question_type": "Supplementary harm evidence",
      "question": "Are grade 3 or worse harm proportions and response benefit displayed separately?",
      "needed": "Original group-specific safety populations, harms, grades, denominators and exposure",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Original group-specific safety populations, harms, grades, denominators and exposure",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original safety populations, group-specific events, exposure, grades, discontinuation and denominators.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "Original grade 3 or worse proportions are preserved: fatigue 16.0% versus 9.6%, muscle spasms 6.5% versus 0.6% and hyponatremia 8.0% versus 3.8%.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not create responder-specific harm counts, new differences, RR, CI or P. Safety-analysis denominators, periods and relatedness remain unread.",
      "missingness": "Do not create responder-specific harm counts, new differences, RR, CI or P. Safety-analysis denominators, periods and relatedness remain unread.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Do not create responder-specific harm counts, new differences, RR, CI or P. Safety-analysis denominators, periods and relatedness remain unread."
    },
    {
      "item_id": "N23",
      "question_type": "Supplementary harm evidence",
      "question": "Was the scope of descriptive safety comparisons and no planned inferential testing retained?",
      "needed": "Prespecified safety plans, descriptive tables, relatedness and testing materials",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Prespecified safety plans, descriptive tables, relatedness and testing materials",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original safety plans, data collection, relatedness and group-specific descriptive tables.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The preserved summary states that more harms were described in the PEGPH20 group and that the protocol did not plan inferential testing.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Descriptive differences are not promoted into statistically significant harm or confirmed causality, and absence of testing is not interpreted as safety.",
      "missingness": "Descriptive differences are not promoted into statistically significant harm or confirmed causality, and absence of testing is not interpreted as safety.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Descriptive differences are not promoted into statistically significant harm or confirmed causality, and absence of testing is not interpreted as safety."
    },
    {
      "item_id": "N24",
      "question_type": "Supplementary harm evidence",
      "question": "Are thrombosis-prophylaxis conditions and gaps in original harm events distinguished?",
      "needed": "Actual prophylaxis, thrombosis events, exposure and group-specific denominators",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Actual prophylaxis, thrombosis events, exposure and group-specific denominators",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Obtain original thrombosis-event, prophylactic-exposure, deviation and safety-denominator materials.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The historical research condition of mandatory enoxaparin prophylaxis in both groups is preserved.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not create original thrombosis-event counts, CI or effects. No prophylaxis or drug-adjustment instructions are given to readers, and safety is not transferred to conditions without prophylaxis.",
      "missingness": "Do not create original thrombosis-event counts, CI or effects. No prophylaxis or drug-adjustment instructions are given to readers, and safety is not transferred to conditions without prophylaxis.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Do not create original thrombosis-event counts, CI or effects. No prophylaxis or drug-adjustment instructions are given to readers, and safety is not transferred to conditions without prophylaxis."
    },
    {
      "item_id": "N25",
      "question_type": "Supplementary harm evidence",
      "question": "Were gaps in other, rare or long-term harms, discontinuation and replication evidence retained?",
      "needed": "All harms, discontinuation, duration, exposure and independent-report relationships",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "All harms, discontinuation, duration, exposure and independent-report relationships",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Complete original safety tables, exposure, discontinuation and long-term or rare-harm materials are needed.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The summary focuses on some severe harms and mandatory prophylaxis.",
      "condition_status": "Unverified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. No new certification of absence of all harms, long-term safety or independent harm replication is made. Numbers, proportions and CI beyond the original summary are absent.",
      "missingness": "No new certification of absence of all harms, long-term safety or independent harm replication is made. Numbers, proportions and CI beyond the original summary are absent.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "No new certification of absence of all harms, long-term safety or independent harm replication is made. Numbers, proportions and CI beyond the original summary are absent."
    },
    {
      "item_id": "N26",
      "question_type": "Supplementary harm evidence",
      "question": "Were other cancers, treatment lines and clinical applications not automatically extended?",
      "needed": "Direct effect or harm materials by population, combination and prophylaxis",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Direct effect or harm materials by population, combination and prophylaxis",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Link direct materials on new populations or combinations to separate questions.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The original materials concern untreated high-expression stage IV pancreatic ductal adenocarcinoma with shared nab-paclitaxel plus gemcitabine and mandatory prophylaxis.",
      "condition_status": "Unverified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not certify efficacy or harms of other cancers, treatment lines or combinations or create treatment-selection, use or substitution recommendations.",
      "missingness": "Do not certify efficacy or harms of other cancers, treatment lines or combinations or create treatment-selection, use or substitution recommendations.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Do not certify efficacy or harms of other cancers, treatment lines or combinations or create treatment-selection, use or substitution recommendations."
    },
    {
      "item_id": "N27",
      "question_type": "Comparative efficacy",
      "question": "Is reading the preserved summary distinguished from reading external papers, registration, protocol or SAP?",
      "needed": "Original URLs, identifiers, individual material types and actual-reading records",
      "role": "Required",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Original URLs, identifiers, individual material types and actual-reading records",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Link original materials acquired by the user to types and access states.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "The complete parent verdict summary was read for production, and the original PubMed URL and NCT02715804 are preserved.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. No new registration URL is constructed from identifiers. All external abstracts, full texts, registration and plans remain unread, and no separate external link tests were performed.",
      "missingness": "No new registration URL is constructed from identifiers. All external abstracts, full texts, registration and plans remain unread, and no separate external link tests were performed.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "No new registration URL is constructed from identifiers. All external abstracts, full texts, registration and plans remain unread, and no separate external link tests were performed."
    },
    {
      "item_id": "N28",
      "question_type": "Comparative efficacy",
      "question": "Are original dates, Korean and English drafts, empty values, verdict and content-review states distinguished?",
      "needed": "Complete preserved summary, verdict record, original assessment axes, history and current production state",
      "role": "Supplementary",
      "role_reason": "Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries",
      "application_exception": "Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety.",
      "criterion": "Complete preserved summary, verdict record, original assessment axes, history and current production state",
      "basis": "Increased objective response",
      "condition_origin": "Question-specific application conditions; existing content review remains incomplete and common definitions are not automatically fulfilled",
      "proposed_research": "Proposal: Reflect additional materials and decisions through preservation of original wording and separate events.",
      "current_reports": [
        "R01"
      ],
      "existence": "Material information recorded in the preserved summary",
      "acquired_read": "Summary read; external materials not read",
      "observation": "2026-08-26, empty correction and deliberation values, Korean and English drafts, parent D34, original false or missing values, empty values and subclaim grade C are preserved. Original review-pending and production-eligibility markers are history.",
      "condition_status": "Partly verified",
      "status_reason": "Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Absent subclaim scores are not filled. Existing content review remains incomplete; activation and completion markers for model, content and boundary review are false, new units are 0 and the final independent total is not recorded.",
      "missingness": "Absent subclaim scores are not filled. Existing content review remains incomplete; activation and completion markers for model, content and boundary review are false, new units are 0 and the final independent total is not recorded.",
      "uncertainty": "Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.",
      "review_date": null,
      "reading_status": "Full text not read · Stored summary read",
      "additional_material": "Absent subclaim scores are not filled. Existing content review remains incomplete; activation and completion markers for model, content and boundary review are false, new units are 0 and the final independent total is not recorded."
    }
  ],
  "reports": [
    {
      "report_id": "R01",
      "title": "Van Cutsem E, Tempero MA, Sigal D, et al. Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma. J Clin Oncol. 2020;38:3185-3194. PMID: 32706635.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/32706635/",
      "report_type": "HALO109-301 randomized phase 3 trial report",
      "existence": "Materials preserved in original citation and evidence lists",
      "acquired_read": "Summary read; external materials not read",
      "study_family": "F01",
      "independent_replication": false,
      "observed_result": "Objective response was 47% versus 36%, ratio 1.29 (95% CI 1.03 to 1.63). The fixed testing sequence required significant overall survival before lower-order confirmatory testing; after survival failed, this result must be interpreted as exploratory. Median progression-free survival was also 7.1 versus 7.1 months, HR 0.97 (95% CI 0.75 to 1.26).",
      "result_level": "Preserved-summary results; ORR is linked from the body, and original evidence-list OS values are not changed into ORR",
      "source_evidence_date": "2026-08-26",
      "materials": [
        {
          "material_type": "local_summary",
          "public_status": "Original source link preserved",
          "access_status": "Summary read",
          "acquired": true,
          "actually_read": "Summary read",
          "as_of": "2026-08-26",
          "qualification": "Preserved parent verdict summary"
        },
        {
          "material_type": "abstract",
          "public_status": "Original source link preserved",
          "access_status": "Not read",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-08-26",
          "qualification": "External material unread; a URL does not mean acquisition, reading or completed review"
        },
        {
          "material_type": "fulltext",
          "public_status": "No separate URL in the original material",
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          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-08-26",
          "qualification": "External material unread; a URL does not mean acquisition, reading or completed review"
        },
        {
          "material_type": "registration",
          "public_status": "No separate URL in the original material",
          "access_status": "Not read",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-08-26",
          "qualification": "External material unread; a URL does not mean acquisition, reading or completed review"
        },
        {
          "material_type": "protocol_sap",
          "public_status": "No separate URL in the original material",
          "access_status": "Not read",
          "acquired": false,
          "actually_read": "Not read",
          "as_of": "2026-08-26",
          "qualification": "External material unread; a URL does not mean acquisition, reading or completed review"
        }
      ],
      "links": [
        {
          "label": "PubMed",
          "url": "https://pubmed.ncbi.nlm.nih.gov/32706635/"
        }
      ]
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      "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": "Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed."
    },
    {
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      "official_principle": "Distinguish studies from reports and link them; do not omit a study solely because results are unreported.",
      "review_level": "Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed."
    },
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      "id": "M08",
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      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08",
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      "official_principle": "Define the outcome and effect of interest, then examine randomization, deviations, missing data, measurement and selective reporting.",
      "review_level": "Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed."
    },
    {
      "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",
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      "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.",
      "review_level": "Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed."
    },
    {
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      "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": "Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed."
    }
  ],
  "status_dictionary": {
    "Partly verified": "Some information exists in the preserved review summary; detailed original materials remain unverified. This does not certify a passed review or clinical efficacy.",
    "Unverified": "Detailed materials for the selected condition could not be established within the stored scope; this does not mean zero effect, zero studies or safety",
    "Review incomplete": "Review of existing content incomplete",
    "Met": "Use only within the relevant conditions after existing content review; no automatic designation in this preparation",
    "Not reported": "Distinguish only within materials actually read; do not turn unread external materials into unreported findings",
    "Inaccessible": "Not applied during this preparation because actual access was not tested",
    "Not applicable": "Use with a reason for non-applicability based on an explicit question boundary",
    "Conflicting data": "Judge after actual material comparison; review was not performed during this preparation",
    "Insufficient evidence for the conditions": "Do not use as a clinical grade encompassing currently unread materials"
  },
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    "unique_trial_count": null,
    "unique_participant_count": null,
    "reason": "HALO109-301 shares the same report, original trial, cohort and two subclaim outcomes; OS, ORR and PFS are not counted as separate new trials. A study-family identifier links relationships and does not certify unique trial counts; reports, endpoints, sibling sheets and the same participants are not newly added as independent evidence."
  },
  "history": [
    {
      "date": "2026-10-11",
      "kind": "Separation of public-facing pages and materials",
      "view_version": "1.0",
      "change": "Public reader pages and material were prepared from the existing 28 items. No new clinical searches, verification-state changes or scoring were performed."
    }
  ],
  "language": "en",
  "translation_date": "2026-10-11"
}