# PEGPH20 add-on therapy × increased objective response — evidence sheet for a lower-order endpoint under fixed-sequence testing Verdict 2939 · Evidence Check Stored-material review date: Not recorded Original evidence cut-off: 2026-08-26 Review-criteria version: 1.0 Public page/material preparation date: 2026-10-11 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: Previously untreated stage IV pancreatic ductal adenocarcinoma with stromal hyaluronan staining of at least 50%; detailed eligibility remains unread - Ingredient, formulation and route: 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 - Measured outcome: 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 - Questions outside this scope: 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 ## Checklist items ### N01 · Are the original objective-response subclaim verdict and parent survival grade D distinguished? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: 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. - Why unverified: 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. - Reason for missing information: 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. - Required materials and conditions: Separate records of subclaim original wording, grade, note and parent context - Materials to obtain first: 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. - Further research: Proposal: Link additional materials separately to the response question and parent survival results. - Conditions for verification: Separate records of subclaim original wording, grade, note and parent context - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N02 · Who was actually eligible for response-rate analysis? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original population was untreated stage IV pancreatic ductal adenocarcinoma with stromal hyaluronan staining of at least 50%. - Why unverified: 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. - Reason for missing information: 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. - Required materials and conditions: Expression, cancer type, stage, treatment line, baseline conditions and denominators - Materials to obtain first: 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. - Further research: Proposal: Obtain original eligibility, baseline tumor, biomarker and assessable analysis-population materials. - Conditions for verification: Expression, cancer type, stage, treatment line, baseline conditions and denominators - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N03 · Were added PEGPH20, matching placebo and shared anticancer treatment separated? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The trial context of nab-paclitaxel plus gemcitabine in both groups, with added PEGPH20 versus matching placebo, is preserved. - Why unverified: 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. - Reason for missing information: 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. - Required materials and conditions: Original drug, placebo, shared-treatment and actual-exposure records - Materials to obtain first: 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. - Further research: Proposal: Obtain original intervention, placebo, shared regimen and actual-exposure materials. - Conditions for verification: Original drug, placebo, shared-treatment and actual-exposure records - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N04 · Are shared thrombosis-prophylaxis conditions and actual management scope retained? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: Both groups had mandatory enoxaparin prophylaxis because of thromboembolic risk. - Why unverified: 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. - Reason for missing information: Research conditions are not converted into prophylactic-medication instructions for readers. Response or safety results are not automatically applied to other conditions without prophylaxis. - Required materials and conditions: Prophylaxis, concomitant management, actual exposure, adherence and denominators - Materials to obtain first: Research conditions are not converted into prophylactic-medication instructions for readers. Response or safety results are not automatically applied to other conditions without prophylaxis. - Further research: Proposal: Obtain original shared-management, prophylactic-exposure, deviation and group-specific event materials. - Conditions for verification: Prophylaxis, concomitant management, actual exposure, adherence and denominators - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N05 · Are 494 randomized participants, 492 ITT participants and response-rate denominators the same? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: 494 participants randomized 2:1 and 492 ITT participants are overall trial information. - Why unverified: 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. - Reason for missing information: 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. - Required materials and conditions: Group-specific allocation, ITT, assessable-imaging and response-analysis denominators - Materials to obtain first: 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. - Further research: Proposal: Obtain original group allocation, response-analysis populations, assessable counts and original responder tables. - Conditions for verification: Group-specific allocation, ITT, assessable-imaging and response-analysis denominators - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N06 · What were objective-response criteria, confirmation, times and assessors? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The preserved summary records objective imaging response as a separate lower-order outcome. - Why unverified: 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. - Reason for missing information: RECIST version, central or institutional assessment, complete or partial response, confirmation schedules and classification methods are absent from the summary and are not created. - Required materials and conditions: Imaging criteria, response types, confirmatory assessments, times and measurement procedures - Materials to obtain first: RECIST version, central or institutional assessment, complete or partial response, confirmation schedules and classification methods are absent from the summary and are not created. - Further research: Proposal: Obtain original response definitions, assessment procedures, assessors, schedules and classification tables. - Conditions for verification: Imaging criteria, response types, confirmatory assessments, times and measurement procedures - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N07 · Were original proportions of 47% versus 36% and missing original responder counts retained? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: Objective response of 47% versus 36% is recorded in the original summary body. - Why unverified: 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. - Reason for missing information: Do not calculate new proportion differences, responder counts, NNT or RR. Group labels, original denominators and missing-assessment handling details remain unread. - Required materials and conditions: Original group-specific proportions, responders, denominators and aggregation rules - Materials to obtain first: Do not calculate new proportion differences, responder counts, NNT or RR. Group labels, original denominators and missing-assessment handling details remain unread. - Further research: Proposal: Obtain original responders, group-specific analysis denominators and aggregation rules. - Conditions for verification: Original group-specific proportions, responders, denominators and aggregation rules - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N08 · Are the response ratio 1.29, CI and new tests distinguished? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The original response ratio is 1.29 (95% CI 1.03 to 1.63). - Why unverified: 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. - Reason for missing information: Do not recalculate from 47/36 or create the ratio model, new P, exact tests, adjustment variables or inferential eligibility. - Required materials and conditions: Original ratio, CI, testing, model, denominator and effect definitions - Materials to obtain first: Do not recalculate from 47/36 or create the ratio model, new P, exact tests, adjustment variables or inferential eligibility. - Further research: Proposal: Obtain original ratio definitions, models, intervals, denominators and testing plans. - Conditions for verification: Original ratio, CI, testing, model, denominator and effect definitions - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N09 · Was the fixed sequence requiring significant survival first preserved? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: 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. - Why unverified: 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. - Reason for missing information: Exclusion of 1 by the CI alone does not promote response into prespecified confirmatory success. - Required materials and conditions: Original plans for testing sequence, alpha, endpoint hierarchy and changes - Materials to obtain first: Exclusion of 1 by the CI alone does not promote response into prespecified confirmatory success. - Further research: Proposal: Obtain original SAP, fixed sequence, alpha, testing and outcome lists. - Conditions for verification: Original plans for testing sequence, alpha, endpoint hierarchy and changes - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N10 · Are the prespecified 2019 amendment, sole primary overall survival and response hierarchy distinguished? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The summary records OS as the sole primary endpoint after the prespecified 2019 amendment and states agreement with NCT02715804. - Why unverified: 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. - Reason for missing information: Response is not newly designated as coprimary. Earlier hierarchy, amendment circumstances and actual registration content remain unread. - Required materials and conditions: Registration, protocol, SAP, dates and decisions before and after amendment - Materials to obtain first: Response is not newly designated as coprimary. Earlier hierarchy, amendment circumstances and actual registration content remain unread. - Further research: Proposal: Obtain original registration history, amendment events, protocol and SAP separately. - Conditions for verification: Registration, protocol, SAP, dates and decisions before and after amendment - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N11 · Were exploratory response signals, clinical importance and confirmatory effects separated? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The preserved summary recognizes improved response itself while stating that it is not a confirmatory conclusion or equivalent to survival benefit. - Why unverified: 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. - Reason for missing information: Do not create clinical-importance thresholds, confirmatory response success or universal treatment benefit absent from the original summary. - Required materials and conditions: Response importance, prespecified success thresholds, hierarchy and original CI - Materials to obtain first: Do not create clinical-importance thresholds, confirmatory response success or universal treatment benefit absent from the original summary. - Further research: Proposal: Obtain original planned importance, response maintenance, clinical links and hierarchy. - Conditions for verification: Response importance, prespecified success thresholds, hierarchy and original CI - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N12 · Were null overall survival and increased response preserved together? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: 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. - Why unverified: 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. - Reason for missing information: Imaging response is not transferred into prolonged OS. The original context that the OS CI retained possible benefit is also not erased. - Required materials and conditions: Original OS medians, HR, CI, P, events and denominators - Materials to obtain first: Imaging response is not transferred into prolonged OS. The original context that the OS CI retained possible benefit is also not erased. - Further research: Proposal: Obtain original OS models, curves, censoring, group-specific events and denominators separately. - Conditions for verification: Original OS medians, HR, CI, P, events and denominators - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N13 · Are null progression-free survival, response duration and progression the same outcome? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: Median PFS of 7.1 versus 7.1 months, HR 0.97 (95% CI 0.75 to 1.26), is preserved. - Why unverified: 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. - Reason for missing information: Positive response is not converted into PFS or response-duration benefit. Response duration, progression times and PFS P remain unread. - Required materials and conditions: PFS, response duration, imaging-response definitions, effects and denominators - Materials to obtain first: Positive response is not converted into PFS or response-duration benefit. Response duration, progression times and PFS P remain unread. - Further research: Proposal: Obtain original PFS, response-duration, persistence and progression definitions and tables. - Conditions for verification: PFS, response duration, imaging-response definitions, effects and denominators - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N14 · Were central allocation, double-blinding and imaging-assessment details separated? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: Central interactive-response-system allocation and double-blinding with matching placebo appear in the preserved summary. - Why unverified: 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. - Reason for missing information: This information alone does not constitute new verification of central imaging assessment, independent assessors or analyst blinding. - Required materials and conditions: Original allocation-concealment, blinding, imaging-assessor and analyst methods - Materials to obtain first: This information alone does not constitute new verification of central imaging assessment, independent assessors or analyst blinding. - Further research: Proposal: Obtain original allocation, imaging-assessment, blinding roles and unblinding procedures. - Conditions for verification: Original allocation-concealment, blinding, imaging-assessor and analyst methods - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N15 · Were gaps in missing response assessments, deviations, progression, death handling and denominators retained? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: Overall ITT information and original response proportions exist, but detailed response-assessment data flow is absent from the summary. - Why unverified: 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. - Reason for missing information: Proportions alone do not establish complete imaging for all patients, death or progression handling or ITT response rules. - Required materials and conditions: Missing imaging assessments, analysis populations, deaths, progression and missing-data rules - Materials to obtain first: Proportions alone do not establish complete imaging for all patients, death or progression handling or ITT response rules. - Further research: Proposal: Obtain original assessable populations, reasons for missing assessments, death or progression handling, missing-data handling and sensitivity materials. - Conditions for verification: Missing imaging assessments, analysis populations, deaths, progression and missing-data rules - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N16 · What gaps remain in response interpretation of actual exposure, anticancer intensity, discontinuation or subsequent treatment? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: Historical intervention, shared anticancer treatment and mandatory prophylaxis conditions are preserved. - Why unverified: 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. - Reason for missing information: Do not newly calculate responder-specific exposure, dose intensity, discontinuation or subsequent-treatment effects absent from the original summary. - Required materials and conditions: Added drug, shared anticancer treatment, prophylaxis, crossover, discontinuation and actual exposure - Materials to obtain first: Do not newly calculate responder-specific exposure, dose intensity, discontinuation or subsequent-treatment effects absent from the original summary. - Further research: Proposal: Obtain original exposure, discontinuation, subsequent management and prespecified effect-of-interest materials. - Conditions for verification: Added drug, shared anticancer treatment, prophylaxis, crossover, discontinuation and actual exposure - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N17 · Were response subgroups, expression analyses and multiple outcomes verified prospectively? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The selected population's staining threshold of at least 50% and lower-order response plans are preserved in the summary. - Why unverified: 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. - Reason for missing information: No additional expression strata, treatment lines, subgroup response counts, P or independent success are created. - Required materials and conditions: Original plans for subgroups, interactions, hierarchy, denominators and testing - Materials to obtain first: No additional expression strata, treatment lines, subgroup response counts, P or independent success are created. - Further research: Proposal: Obtain original subgroup, biomarker, interaction, multiplicity and effect materials. - Conditions for verification: Original plans for subgroups, interactions, hierarchy, denominators and testing - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N18 · Were mechanisms and imaging shrinkage not converted into clinical function or survival benefit? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The preserved summary explicitly states that imaging response must not be promoted into survival benefit. - Why unverified: 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. - Reason for missing information: 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. - Required materials and conditions: Separate materials for response, mechanisms and direct clinical function or survival - Materials to obtain first: 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. - Further research: Proposal: Obtain direct endpoints, effects and denominators separately for clinical-function, symptom and survival questions. - Conditions for verification: Separate materials for response, mechanisms and direct clinical function or survival - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N19 · Were the same HALO report, cohort and two endpoints not added as independent evidence? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The two sheets share one HALO109-301 literature record, NCT02715804 and the 494/492-participant context. - Why unverified: 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. - Reason for missing information: Response, OS, PFS and sibling sheets are not added as new independent trials or participants. Final independent and total-participant counts remain unrecorded. - Required materials and conditions: Relationships among original trial, report, shared participants, times and sibling sheets - Materials to obtain first: Response, OS, PFS and sibling sheets are not added as new independent trials or participants. Final independent and total-participant counts remain unrecorded. - Further research: Proposal: Link new reports to existing trial and registration identifiers and relationships. - Conditions for verification: Relationships among original trial, report, shared participants, times and sibling sheets - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N20 · Were Halozyme support, drug or placebo, 2 employees and Paragon writing separated? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: Halozyme sponsorship and support, protocol, drug or placebo, data management, 2 company authors and Paragon medical writing paid by Halozyme are preserved. - Why unverified: 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. - Reason for missing information: Paragon writing is not converted into outsourced analysis. Employee identities, statistical-analysis and data-access role details remain unread. - Required materials and conditions: Cash support, products, affiliations, management and external analysis or writing roles - Materials to obtain first: Paragon writing is not converted into outsourced analysis. Employee identities, statistical-analysis and data-access role details remain unread. - Further research: Proposal: Obtain each support, supply, affiliation, analysis, management and writing disclosure. - Conditions for verification: Cash support, products, affiliations, management and external analysis or writing roles - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N21 · Were original R1 and I0 and unverified independent replication retained? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: Parent R1 and I0 and the original wording that the confirmed efficacy trial was one manufacturer development trial are retained. - Why unverified: 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. - Reason for missing information: Positive response or two outcomes do not certify independent replication by other investigators or funding sources. - Required materials and conditions: Relationships among manufacturer trial, funding, investigators and original verdict - Materials to obtain first: Positive response or two outcomes do not certify independent replication by other investigators or funding sources. - Further research: Proposal: Link study, funding, author and denominator relationships of additional materials separately. - Conditions for verification: Relationships among manufacturer trial, funding, investigators and original verdict - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N22 · Are grade 3 or worse harm proportions and response benefit displayed separately? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: 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%. - Why unverified: 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. - Reason for missing information: Do not create responder-specific harm counts, new differences, RR, CI or P. Safety-analysis denominators, periods and relatedness remain unread. - Required materials and conditions: Original group-specific safety populations, harms, grades, denominators and exposure - Materials to obtain first: Do not create responder-specific harm counts, new differences, RR, CI or P. Safety-analysis denominators, periods and relatedness remain unread. - Further research: Proposal: Obtain original safety populations, group-specific events, exposure, grades, discontinuation and denominators. - Conditions for verification: Original group-specific safety populations, harms, grades, denominators and exposure - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N23 · Was the scope of descriptive safety comparisons and no planned inferential testing retained? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The preserved summary states that more harms were described in the PEGPH20 group and that the protocol did not plan inferential testing. - Why unverified: 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. - Reason for missing information: Descriptive differences are not promoted into statistically significant harm or confirmed causality, and absence of testing is not interpreted as safety. - Required materials and conditions: Prespecified safety plans, descriptive tables, relatedness and testing materials - Materials to obtain first: Descriptive differences are not promoted into statistically significant harm or confirmed causality, and absence of testing is not interpreted as safety. - Further research: Proposal: Obtain original safety plans, data collection, relatedness and group-specific descriptive tables. - Conditions for verification: Prespecified safety plans, descriptive tables, relatedness and testing materials - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N24 · Are thrombosis-prophylaxis conditions and gaps in original harm events distinguished? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The historical research condition of mandatory enoxaparin prophylaxis in both groups is preserved. - Why unverified: 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. - Reason for missing information: 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. - Required materials and conditions: Actual prophylaxis, thrombosis events, exposure and group-specific denominators - Materials to obtain first: 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. - Further research: Proposal: Obtain original thrombosis-event, prophylactic-exposure, deviation and safety-denominator materials. - Conditions for verification: Actual prophylaxis, thrombosis events, exposure and group-specific denominators - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N25 · Were gaps in other, rare or long-term harms, discontinuation and replication evidence retained? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The summary focuses on some severe harms and mandatory prophylaxis. - Why unverified: 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. - Reason for missing information: 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. - Required materials and conditions: All harms, discontinuation, duration, exposure and independent-report relationships - Materials to obtain first: 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. - Further research: Proposal: Complete original safety tables, exposure, discontinuation and long-term or rare-harm materials are needed. - Conditions for verification: All harms, discontinuation, duration, exposure and independent-report relationships - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N26 · Were other cancers, treatment lines and clinical applications not automatically extended? Verification status: Unverified Reading scope: Summary read; external materials not read - Current findings: The original materials concern untreated high-expression stage IV pancreatic ductal adenocarcinoma with shared nab-paclitaxel plus gemcitabine and mandatory prophylaxis. - Why unverified: 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. - Reason for missing information: Do not certify efficacy or harms of other cancers, treatment lines or combinations or create treatment-selection, use or substitution recommendations. - Required materials and conditions: Direct effect or harm materials by population, combination and prophylaxis - Materials to obtain first: Do not certify efficacy or harms of other cancers, treatment lines or combinations or create treatment-selection, use or substitution recommendations. - Further research: Proposal: Link direct materials on new populations or combinations to separate questions. - Conditions for verification: Direct effect or harm materials by population, combination and prophylaxis - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N27 · Is reading the preserved summary distinguished from reading external papers, registration, protocol or SAP? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: The complete parent verdict summary was read for production, and the original PubMed URL and NCT02715804 are preserved. - Why unverified: 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. - Reason for missing information: 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. - Required materials and conditions: Original URLs, identifiers, individual material types and actual-reading records - Materials to obtain first: 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. - Further research: Proposal: Link original materials acquired by the user to types and access states. - Conditions for verification: Original URLs, identifiers, individual material types and actual-reading records - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ### N28 · Are original dates, Korean and English drafts, empty values, verdict and content-review states distinguished? Verification status: Partly verified Reading scope: Summary read; external materials not read - Current findings: 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. - Why unverified: 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. - Reason for missing information: 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. - Required materials and conditions: Complete preserved summary, verdict record, original assessment axes, history and current production state - Materials to obtain first: 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. - Further research: Proposal: Reflect additional materials and decisions through preservation of original wording and separate events. - Conditions for verification: Complete preserved summary, verdict record, original assessment axes, history and current production state - Why this condition is needed: Individual application conditions documenting the selected endpoint, original values, denominators, hierarchy and applicability boundaries - Application exceptions: Externally unread materials, other endpoints or out-of-scope results do not replace condition fulfillment, zero effect or safety. - Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification. - Referenced methods: Increased objective response - Related sources: R01 ## Evidence and sources ### R01 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. [PubMed](https://pubmed.ncbi.nlm.nih.gov/32706635/) Materials actually read: Summary read; external materials not read Findings recorded in the summary: 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). Record level: Preserved-summary results; ORR is linked from the body, and original evidence-list OS values are not changed into ORR Independent replication: 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | local_summary | Original source link preserved | Summary read | Summary read | Preserved parent verdict summary | | abstract | Original source link preserved | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review | | fulltext | No separate URL in the original material | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review | | registration | No separate URL in the original material | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review | | protocol_sap | No separate URL in the original material | Not read | Not read | External material unread; a URL does not mean acquisition, reading or completed review | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions and reasons for changes, and distinguish variations in interventions. · Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed. - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish studies from reports and link them; do not omit a study solely because results are unreported. · Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed. - M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Define the outcome and effect of interest, then examine randomization, deviations, missing data, measurement and selective reporting. · Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed. - M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed. - M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence rates. · Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed. ## What the statuses mean - 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 ## Change history 2026-10-11 · Public page/materials 1.0. Public reader pages and material were prepared from the existing 28 items. No new clinical searches, verification-state changes or scoring were performed.