# PEGPH20 add-on therapy × improved overall survival — evidence sheet for hyaluronan-high metastatic pancreatic ductal adenocarcinoma

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 primary overall survival; ORR, PFS and harms preserved separately
- 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 · Were the original overall-survival subclaim verdict and parent context preserved separately?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The selected original claim is improved overall survival, subclaim grade D, with a null-result note of HR 1.00 and P=.97. Parent D, 34 points and Caution are preserved as separate context.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Subclaim score, status and axes are absent and are not filled with parent values. This is not a new grade assessment.
- Reason for missing information: Subclaim score, status and axes are absent and are not filled with parent values. This is not a new grade assessment.
- Required materials and conditions: Separate records of the original claim, grade, note and parent values
- Materials to obtain first: Subclaim score, status and axes are absent and are not filled with parent values. This is not a new grade assessment.
- Further research: Proposal: Link additional materials separately to the selected survival question and parent context.
- Conditions for verification: Separate records of the original claim, grade, note and parent values
- 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: Improved overall survival
- Related sources: R01

### N02 · Who were the hyaluronan-high, untreated stage IV pancreatic ductal adenocarcinoma participants?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The trial recruited previously untreated stage IV pancreatic ductal adenocarcinoma patients 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 results to other expression levels, stages, treatment lines or cancers. Detailed eligibility and baseline conditions remain unread.
- Reason for missing information: Do not automatically apply results to other expression levels, stages, treatment lines or cancers. Detailed eligibility and baseline conditions remain unread.
- Required materials and conditions: Original tumor, expression, treatment-history, stage, eligibility and denominator materials
- Materials to obtain first: Do not automatically apply results to other expression levels, stages, treatment lines or cancers. Detailed eligibility and baseline conditions remain unread.
- Further research: Proposal: Obtain original eligibility, baseline characteristics, biomarker-assessment methods and denominators.
- Conditions for verification: Original tumor, expression, treatment-history, stage, eligibility and denominator 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: Improved overall survival
- Related sources: R01

### N03 · Were PEGPH20 add-on therapy and shared anticancer treatment distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The intervention was PEGPH20 add-on therapy; both groups received nab-paclitaxel plus gemcitabine.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. The added drug's effect is not converted into the overall effect of shared anticancer treatment. Dose, schedule and actual-exposure details remain unread, and no treatment instructions are created.
- Reason for missing information: The added drug's effect is not converted into the overall effect of shared anticancer treatment. Dose, schedule and actual-exposure details remain unread, and no treatment instructions are created.
- Required materials and conditions: Records of study drug, placebo, shared regimen, actual exposure and concomitant-treatment management
- Materials to obtain first: The added drug's effect is not converted into the overall effect of shared anticancer treatment. Dose, schedule and actual-exposure details remain unread, and no treatment instructions are created.
- Further research: Proposal: Link original intervention, placebo, shared regimen, actual exposure and discontinuation materials.
- Conditions for verification: Records of study drug, placebo, shared regimen, actual exposure and concomitant-treatment management
- 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: Improved overall survival
- Related sources: R01

### N04 · What were the shared research conditions for matching placebo and thrombosis prophylaxis?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Matching placebo was used, and 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 prophylaxis or medication instructions for readers. The same results are not certified for other prophylaxis or exposure conditions.
- Reason for missing information: Research conditions are not converted into prophylaxis or medication instructions for readers. The same results are not certified for other prophylaxis or exposure conditions.
- Required materials and conditions: Original placebo, shared prophylaxis, co-exposure and adherence materials
- Materials to obtain first: Research conditions are not converted into prophylaxis or medication instructions for readers. The same results are not certified for other prophylaxis or exposure conditions.
- Further research: Proposal: Obtain original protocol materials on shared management, actual exposure, deviations and concomitant treatments.
- Conditions for verification: Original placebo, shared prophylaxis, co-exposure and adherence 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: Improved overall survival
- Related sources: R01

### N05 · Were 494 randomized participants, 492 ITT participants and 2:1 allocation distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The record states that 492 of 494 participants randomized 2:1 were included in the ITT analysis.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not calculate group sizes from 2:1 or fill every endpoint and safety denominator with 492. Exclusion reasons and group-specific analysis sizes remain unread.
- Reason for missing information: Do not calculate group sizes from 2:1 or fill every endpoint and safety denominator with 492. Exclusion reasons and group-specific analysis sizes remain unread.
- Required materials and conditions: Group-specific allocation, ITT, exclusions and outcome-specific analysis denominators
- Materials to obtain first: Do not calculate group sizes from 2:1 or fill every endpoint and safety denominator with 492. Exclusion reasons and group-specific analysis sizes remain unread.
- Further research: Proposal: Obtain original participant flow, group allocation, ITT exclusions and outcome-specific denominators.
- Conditions for verification: Group-specific allocation, ITT, exclusions and outcome-specific 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: Improved overall survival
- Related sources: R01

### N06 · What were the overall-survival definitions for start time, death ascertainment, follow-up and censoring?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The original primary endpoint was overall survival; 330 of 492 ITT participants died.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not create death-ascertainment methods, data cutoffs, censoring, group-specific deaths or follow-up details. Do not duplicate 330 as each group's event count.
- Reason for missing information: Do not create death-ascertainment methods, data cutoffs, censoring, group-specific deaths or follow-up details. Do not duplicate 330 as each group's event count.
- Required materials and conditions: Original survival-time, start-point, death, censoring, follow-up and denominator materials
- Materials to obtain first: Do not create death-ascertainment methods, data cutoffs, censoring, group-specific deaths or follow-up details. Do not duplicate 330 as each group's event count.
- Further research: Proposal: Obtain original survival definitions, death ascertainment, censoring, follow-up and group-specific event tables.
- Conditions for verification: Original survival-time, start-point, death, censoring, follow-up and denominator 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: Improved overall survival
- Related sources: R01

### N07 · Were median overall survival and HR, CI and P preserved as original values?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Median overall survival was 11.2 versus 11.5 months, HR 1.00 (95% CI 0.80 to 1.27), P=.97.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not calculate median differences, survival proportions, new HR, NNT or restricted means. Median CI and model details remain unread.
- Reason for missing information: Do not calculate median differences, survival proportions, new HR, NNT or restricted means. Median CI and model details remain unread.
- Required materials and conditions: Group-specific medians, between-group HR, CI, tests, models and denominators
- Materials to obtain first: Do not calculate median differences, survival proportions, new HR, NNT or restricted means. Median CI and model details remain unread.
- Further research: Proposal: Obtain original survival curves, median CI, models, group-specific denominators and tests.
- Conditions for verification: Group-specific medians, between-group HR, CI, tests, models 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: Improved overall survival
- Related sources: R01

### N08 · Were the null HR 1.00 result and remaining possible benefit distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The parent records D34 for null overall survival while stating that the CI retained possible benefit.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. A point estimate of 1.00 is not converted into certification of zero effect, equivalence or exclusion of meaningful benefit. Clinical-importance and success-HR threshold details remain unread.
- Reason for missing information: A point estimate of 1.00 is not converted into certification of zero effect, equivalence or exclusion of meaningful benefit. Clinical-importance and success-HR threshold details remain unread.
- Required materials and conditions: Original CI, prespecified success or importance thresholds and effect interpretation
- Materials to obtain first: A point estimate of 1.00 is not converted into certification of zero effect, equivalence or exclusion of meaningful benefit. Clinical-importance and success-HR threshold details remain unread.
- Further research: Proposal: Obtain original planned clinical-importance criteria, testing assumptions and effect CI.
- Conditions for verification: Original CI, prespecified success or importance thresholds and effect interpretation
- 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: Improved overall survival
- Related sources: R01

### N09 · Were the prespecified 2019 amendment and sole primary overall-survival endpoint preserved?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The preserved summary records overall survival as the sole primary endpoint after a 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. Do not infer earlier endpoints, amendment dates or data-access circumstances. Registration and plans were not compared in this production.
- Reason for missing information: Do not infer earlier endpoints, amendment dates or data-access circumstances. Registration and plans were not compared in this production.
- Required materials and conditions: Records of original registration, protocol, SAP, dates and decisions before and after amendment
- Materials to obtain first: Do not infer earlier endpoints, amendment dates or data-access circumstances. Registration and plans were not compared in this production.
- Further research: Proposal: Obtain original registration history, protocol, SAP and amendment events separately.
- Conditions for verification: Records of original 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: Improved overall survival
- Related sources: R01

### N10 · What was the response-rate hierarchy in fixed-sequence testing?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Overall survival had to be significant first before lower-order endpoints could be tested confirmatorily. The record states that response was 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. Positive response does not replace primary survival success, and the testing hierarchy is not newly changed.
- Reason for missing information: Positive response does not replace primary survival success, and the testing hierarchy is not newly changed.
- Required materials and conditions: Original plans for OS, lower-order endpoints, testing sequence and multiplicity
- Materials to obtain first: Positive response does not replace primary survival success, and the testing hierarchy is not newly changed.
- Further research: Proposal: Obtain original SAP materials on fixed sequence, outcome lists, changes and endpoint-specific tests.
- Conditions for verification: Original plans for OS, lower-order endpoints, testing sequence and multiplicity
- 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: Improved overall survival
- Related sources: R01

### N11 · Were objective response of 47% versus 36% and survival separated?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Original response was 47% versus 36%, ratio 1.29 (95% CI 1.03 to 1.63). Its exploratory lower-order status is preserved.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Response ratio and intervals are not copied into OS HR or CI. Responder counts, new proportion differences and P are not calculated.
- Reason for missing information: Response ratio and intervals are not copied into OS HR or CI. Responder counts, new proportion differences and P are not calculated.
- Required materials and conditions: Separate records of imaging-response definitions, denominators, ratio, CI and hierarchy
- Materials to obtain first: Response ratio and intervals are not copied into OS HR or CI. Responder counts, new proportion differences and P are not calculated.
- Further research: Proposal: Obtain original response definitions, assessments, denominators and hierarchy materials separately.
- Conditions for verification: Separate records of imaging-response definitions, denominators, ratio, CI and hierarchy
- 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: Improved overall survival
- Related sources: R01

### N12 · Were the definitions and effects of progression-free and overall survival distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The record gives median PFS of 7.1 versus 7.1 months, HR 0.97 (95% CI 0.75 to 1.26).
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. PFS values and intervals are not transferred into OS values. PFS testing P, assessment procedures and hierarchy details remain unread.
- Reason for missing information: PFS values and intervals are not transferred into OS values. PFS testing P, assessment procedures and hierarchy details remain unread.
- Required materials and conditions: PFS and OS events, times, denominators, effects and CI
- Materials to obtain first: PFS values and intervals are not transferred into OS values. PFS testing P, assessment procedures and hierarchy details remain unread.
- Further research: Proposal: Obtain original PFS definitions, models, denominators, plans and tests separately.
- Conditions for verification: PFS and OS events, times, denominators, effects and 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: Improved overall survival
- Related sources: R01

### N13 · What was the scope of original allocation-concealment and blinding methods?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The original summary records 2:1 allocation through a central interactive response system and use of double-blinding with matching placebo.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not newly certify each assessor or analyst role, code breaking or actual implementation details. Parent B0 is historical.
- Reason for missing information: Do not newly certify each assessor or analyst role, code breaking or actual implementation details. Parent B0 is historical.
- Required materials and conditions: Central allocation, concealment and participant, assessor or analyst procedures
- Materials to obtain first: Do not newly certify each assessor or analyst role, code breaking or actual implementation details. Parent B0 is historical.
- Further research: Proposal: Obtain original methods, allocation, blinding roles and unblinding procedures.
- Conditions for verification: Central allocation, concealment and participant, assessor or analyst 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: Improved overall survival
- Related sources: R01

### N14 · Were gaps in ITT, missing-data, censoring and subsequent-treatment handling retained?

Verification status: Unverified  
Reading scope: Summary read; external materials not read

- Current findings: 492 ITT participants 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. Complete follow-up, group-specific censoring, crossover, subsequent anticancer treatment and missing-data sensitivity are not newly specified.
- Reason for missing information: Complete follow-up, group-specific censoring, crossover, subsequent anticancer treatment and missing-data sensitivity are not newly specified.
- Required materials and conditions: Original analysis-population, model, censoring, deviation, subsequent-treatment and sensitivity materials
- Materials to obtain first: Complete follow-up, group-specific censoring, crossover, subsequent anticancer treatment and missing-data sensitivity are not newly specified.
- Further research: Proposal: Obtain original SAP, analysis-population, follow-up, censoring, subsequent-treatment and sensitivity materials.
- Conditions for verification: Original analysis-population, model, censoring, deviation, subsequent-treatment and sensitivity 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: Improved overall survival
- Related sources: R01

### N15 · Is there information on actual drug exposure, discontinuation and anticancer dose intensity?

Verification status: Unverified  
Reading scope: Summary read; external materials not read

- Current findings: Add-on therapy, shared anticancer treatment and mandatory prophylaxis conditions 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. Exposure duration, dose intensity, discontinuation, crossover and adherence effects remain unread. Exposure is not converted into treatment recommendations.
- Reason for missing information: Exposure duration, dose intensity, discontinuation, crossover and adherence effects remain unread. Exposure is not converted into treatment recommendations.
- Required materials and conditions: Actual exposure, adherence and discontinuation for the added drug, shared regimen and prophylactic drug
- Materials to obtain first: Exposure duration, dose intensity, discontinuation, crossover and adherence effects remain unread. Exposure is not converted into treatment recommendations.
- Further research: Proposal: Obtain original exposure, discontinuation, group-specific concomitant-treatment and prespecified effect-of-interest materials.
- Conditions for verification: Actual exposure, adherence and discontinuation for the added drug, shared regimen and prophylactic drug
- 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: Improved overall survival
- Related sources: R01

### N16 · Was survival not filled in from mechanisms, hyaluronan selection or imaging response?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Selection for hyaluronan staining of at least 50% and improved imaging response appear in the preserved summary, but survival was null.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Mechanistic explanations, selected biomarkers and imaging changes do not replace OS benefit. No mechanistic numbers or additional subgroup effects are created.
- Reason for missing information: Mechanistic explanations, selected biomarkers and imaging changes do not replace OS benefit. No mechanistic numbers or additional subgroup effects are created.
- Required materials and conditions: Relationships between biomarker, mechanism, imaging and direct survival
- Materials to obtain first: Mechanistic explanations, selected biomarkers and imaging changes do not replace OS benefit. No mechanistic numbers or additional subgroup effects are created.
- Further research: Proposal: Link original mechanism and biomarker analysis plans separately to direct survival materials.
- Conditions for verification: Relationships between biomarker, mechanism, imaging and direct 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: Improved overall survival
- Related sources: R01

### N17 · Were gaps in prespecified subgroups, sensitivity and long-term survival retained?

Verification status: Unverified  
Reading scope: Summary read; external materials not read

- Current findings: The selected high-expression population and overall ITT survival results are preserved as recorded.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not generate subgroup numbers, effects, P or long-term survival proportions absent from the original summary. Median survival is not converted into follow-up duration.
- Reason for missing information: Do not generate subgroup numbers, effects, P or long-term survival proportions absent from the original summary. Median survival is not converted into follow-up duration.
- Required materials and conditions: Original subgroup, interaction, follow-up, model, denominator and multiplicity materials
- Materials to obtain first: Do not generate subgroup numbers, effects, P or long-term survival proportions absent from the original summary. Median survival is not converted into follow-up duration.
- Further research: Proposal: Obtain original subgroup, interaction, long-term follow-up and sensitivity materials.
- Conditions for verification: Original subgroup, interaction, follow-up, model, denominator and multiplicity 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: Improved overall survival
- Related sources: R01

### N18 · Were the same HALO report, two outcomes and sibling sheets 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 report and the 494/492-participant context. The parent wording that the originally confirmed efficacy evidence was one manufacturer development trial is retained.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Do not add sheets, endpoints or repeated participant displays as new independent trials or participants. Final independent and total-participant counts remain unrecorded.
- Reason for missing information: Do not add sheets, endpoints or repeated participant displays as new independent trials or participants. Final independent and total-participant counts remain unrecorded.
- Required materials and conditions: Links among original trial, report, shared population, endpoints and times
- Materials to obtain first: Do not add sheets, endpoints or repeated participant displays as new independent trials or participants. Final independent and total-participant counts remain unrecorded.
- Further research: Proposal: Link additional reports to the same registration and trial identifiers and their relationships.
- Conditions for verification: Links among original trial, report, shared population, endpoints and times
- 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: Improved overall survival
- Related sources: R01

### N19 · Were Halozyme funding, products, employee authors, management and writing roles separated?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Halozyme sponsorship and support, protocol, study drug or placebo and data management; 2 company-employee 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. Data-analysis roles and employee-identity details remain unread.
- Reason for missing information: Paragon writing is not converted into outsourced analysis. Data-analysis roles and employee-identity details remain unread.
- Required materials and conditions: Separate records of cash support, drug or placebo supply, affiliations and external analysis or writing
- Materials to obtain first: Paragon writing is not converted into outsourced analysis. Data-analysis roles and employee-identity details remain unread.
- Further research: Proposal: Obtain original disclosures separately for funding, supply, affiliations, data management, analysis and writing roles.
- Conditions for verification: Separate records of cash support, drug or placebo supply, affiliations and external analysis or writing
- 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: Improved overall survival
- Related sources: R01

### N20 · Were original independence, R1 and I0 axes distinguished from new certification?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Parent R1 and I0 and the original manufacturer-development-trial context 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 external efficacy trial, independent replication or investigator certification is created. Original axes are not copied into absent subclaim values.
- Reason for missing information: No new external efficacy trial, independent replication or investigator certification is created. Original axes are not copied into absent subclaim values.
- Required materials and conditions: Preservation of original verdict, support, investigators and report relationships
- Materials to obtain first: No new external efficacy trial, independent replication or investigator certification is created. Original axes are not copied into absent subclaim values.
- Further research: Proposal: If other materials are provided, separately link only study, funding, author and denominator relationships.
- Conditions for verification: Preservation of original verdict, support, investigators and 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: Improved overall survival
- Related sources: R01

### N21 · Were original grade 3 or worse fatigue, muscle-spasm and hyponatremia proportions retained?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Fatigue of 16.0% versus 9.6%, muscle spasms of 6.5% versus 0.6% and hyponatremia of 8.0% versus 3.8% are original grade 3 or worse proportions.
- 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 harm differences, RR, P, CI or event counts. Group-specific safety-analysis denominators, collection periods and relatedness details remain unread.
- Reason for missing information: Do not calculate new harm differences, RR, P, CI or event counts. Group-specific safety-analysis denominators, collection periods and relatedness details remain unread.
- Required materials and conditions: Original group-specific harm definitions, denominators, grades, relatedness and exposure tables
- Materials to obtain first: Do not calculate new harm differences, RR, P, CI or event counts. Group-specific safety-analysis denominators, collection periods and relatedness details remain unread.
- Further research: Proposal: Obtain original safety-population, group-specific event, denominator, grade and exposure tables.
- Conditions for verification: Original group-specific harm definitions, denominators, grades, relatedness and exposure tables
- 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: Improved overall survival
- Related sources: R01

### N22 · Were descriptively more frequent harms and inferential-testing plans distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The preserved summary records descriptively more frequent harms in the PEGPH20 group and states that the protocol did not plan inferential safety 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 converted into absence of harm.
- Reason for missing information: Descriptive differences are not promoted into statistically significant harm or confirmed causality, and absence of testing is not converted into absence of harm.
- Required materials and conditions: Prespecified safety plans, tests, effects, intervals and relatedness
- Materials to obtain first: Descriptive differences are not promoted into statistically significant harm or confirmed causality, and absence of testing is not converted into absence of harm.
- Further research: Proposal: Obtain original safety plans, descriptive tables, relatedness and follow-up materials separately.
- Conditions for verification: Prespecified safety plans, tests, effects, intervals and relatedness
- 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: Improved overall survival
- Related sources: R01

### N23 · Were thrombosis risk, shared enoxaparin and safety-applicability boundaries separated?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The original condition of mandatory prophylaxis in both groups because of thromboembolic risk is preserved.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. The same safety is not applied to conditions without prophylaxis, and no prophylactic-drug instructions are given to readers. Thrombosis event counts and CI are absent from the summary.
- Reason for missing information: The same safety is not applied to conditions without prophylaxis, and no prophylactic-drug instructions are given to readers. Thrombosis event counts and CI are absent from the summary.
- Required materials and conditions: Risk management, shared prophylaxis, actual exposure, events and denominators
- Materials to obtain first: The same safety is not applied to conditions without prophylaxis, and no prophylactic-drug instructions are given to readers. Thrombosis event counts and CI are absent from the summary.
- Further research: Proposal: Obtain original thrombosis-event, prophylactic-exposure, deviation and group-specific denominator materials.
- Conditions for verification: Risk management, shared prophylaxis, actual exposure, 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: Improved overall survival
- Related sources: R01

### N24 · Do gaps remain in other, rare or long-term harms and discontinuation?

Verification status: Unverified  
Reading scope: Summary read; external materials not read

- Current findings: The current preserved summary focuses on some grade 3 or worse harms and prophylaxis conditions.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. This summary does not newly establish all harms, discontinuations, long-term harms or safety.
- Reason for missing information: This summary does not newly establish all harms, discontinuations, long-term harms or safety.
- Required materials and conditions: Original serious-event, discontinuation, exposure, follow-up and direct-harm materials
- Materials to obtain first: This summary does not newly establish all harms, discontinuations, long-term harms or safety.
- Further research: Proposal: Obtain complete original safety tables, exposure, discontinuation, serious or rare-event and long-term materials.
- Conditions for verification: Original serious-event, discontinuation, exposure, follow-up and direct-harm 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: Improved overall survival
- Related sources: R01

### N25 · Were effects or harms not generalized to other cancers, treatment lines or combinations?

Verification status: Unverified  
Reading scope: Summary read; external materials not read

- Current findings: The trial concerns add-on therapy in untreated high-expression stage IV pancreatic ductal adenocarcinoma with specified shared regimen and prophylaxis conditions.
- 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 for other cancers, treatment lines or prophylaxis conditions or create treatment or drug-substitution instructions.
- Reason for missing information: Do not certify efficacy or harms for other cancers, treatment lines or prophylaxis conditions or create treatment or drug-substitution instructions.
- Required materials and conditions: Direct comparative and safety materials by population, exposure and combination
- Materials to obtain first: Do not certify efficacy or harms for other cancers, treatment lines or prophylaxis conditions or create treatment or drug-substitution instructions.
- Further research: Proposal: Link direct materials on new populations or combinations to separate questions if provided.
- Conditions for verification: Direct comparative and safety materials by population, exposure and combination
- 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: Improved overall survival
- Related sources: R01

### N26 · Were actual access to the preserved summary, external papers, registration and plans distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The entire parent preserved 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 URL is created from registration identifiers. Abstracts, full texts, registration, protocol and SAP remain unread, and no separate external link tests were performed.
- Reason for missing information: No new URL is created from registration identifiers. Abstracts, full texts, registration, protocol and SAP remain unread, and no separate external link tests were performed.
- Required materials and conditions: Original source links, registration identifiers and material-specific reading states
- Materials to obtain first: No new URL is created from registration identifiers. Abstracts, full texts, registration, protocol and SAP remain unread, and no separate external link tests were performed.
- Further research: Proposal: Link materials acquired by the user to individual types and access states.
- Conditions for verification: Original source links, registration identifiers and material-specific reading states
- 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: Improved overall survival
- Related sources: R01

### N27 · Were original dates, Korean and English drafts, false or missing values, empty values and verdict history preserved?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: The date 2026-08-26, empty correction and deliberation values, original Korean and English drafts, D34, false or missing axis values and empty values, and the true marker for failure of the primary endpoint with a positive secondary result are preserved.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. Historical cross-checking is not used as current review completion. Absent subclaim scores are not filled with parent scores.
- Reason for missing information: Historical cross-checking is not used as current review completion. Absent subclaim scores are not filled with parent scores.
- Required materials and conditions: Separate records of the complete preserved summary, subclaim verdict, parent values, corrections and history
- Materials to obtain first: Historical cross-checking is not used as current review completion. Absent subclaim scores are not filled with parent scores.
- Further research: Proposal: Link new materials or decisions to separate change events while preserving original text.
- Conditions for verification: Separate records of the complete preserved summary, subclaim verdict, parent values, corrections and history
- 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: Improved overall survival
- Related sources: R01

### N28 · Were production completion, incomplete existing-content review and independence status distinguished?

Verification status: Partly verified  
Reading scope: Summary read; external materials not read

- Current findings: Original review-pending and production-eligibility markers and boundary-review requirements are preserved as history. Existing content review remains incomplete; activation and completion markers for model, content and boundary review are false.
- Why unverified: Only the relevant preserved-summary information is recorded; detailed original materials remain unread and existing content review remains incomplete. No new verdict, split or independence certification exists; new units are 0 and the final independent total is not recorded.
- Reason for missing information: No new verdict, split or independence certification exists; new units are 0 and the final independent total is not recorded.
- Required materials and conditions: Existing candidate history and current production or review states
- Materials to obtain first: No new verdict, split or independence certification exists; new units are 0 and the final independent total is not recorded.
- Further research: Proposal: Reflect only user-provided materials or decisions as separate events.
- Conditions for verification: Existing candidate history and current production or review states
- 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: Improved overall survival
- 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: Median OS 11.2 versus 11.5 months; HR 1.00 (95% CI 0.80 to 1.27), P=.97; 330 deaths  
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.