evt_NCT03025035_v20_v21_277ca9725ed5

{
  "changed_paths": [
    "/protocolSection/statusModule/statusVerifiedDate",
    "/protocolSection/statusModule/lastUpdateSubmitDate",
    "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
    "/protocolSection/outcomesModule/primaryOutcomes/0/description",
    "/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
    "/protocolSection/outcomesModule/primaryOutcomes/0/reviewUnit",
    "/resultsSection/participantFlowModule/groups/0/description",
    "/resultsSection/outcomeMeasuresModule/outcomeMeasures/0/description",
    "/resultsSection/outcomeMeasuresModule/outcomeMeasures/0/timeFrame",
    "/resultsSection/outcomeMeasuresModule/outcomeMeasures/0/reviewUnit",
    "/resultsSection/adverseEventsModule/eventGroups/0/deathsNumAffected",
    "/resultsSection/adverseEventsModule/allCauseMortalityReviewUnit",
    "/annotationSection/annotationModule/unpostedAnnotation/unpostedEvents/0/date",
    "/reviewUnit"
  ],
  "citation_text": "TrialDiff Evidence Record evt_NCT03025035_v20_v21_277ca9725ed5. ClinicalTrials.gov NCT03025035, versions 20-21. Evidence version 1.",
  "claims_not_supported": [
    "That the amendment was scientifically unjustified.",
    "That the change constitutes misconduct or wrongdoing.",
    "That sponsor intent can be inferred from this registry change.",
    "That the change caused or altered the trial's results.",
    "That the change was or was not disclosed in a manuscript.",
    "That TrialDiff determines regulatory compliance or non-compliance.",
    "That co-occurrence with results posting proves the outcome edit was harmless, administrative, or substantively benign.",
    "That event-class membership is a validated global review-priority ranking."
  ],
  "claims_supported": [
    "TrialDiff compared ClinicalTrials.gov record version 20 to version 21 for NCT03025035.",
    "The JSON Patch for this comparison has hash d4561d4b724a3304f5a3f34d9a6b7bbba44033ddb18f419e562e385f0e1205a8.",
    "The active deterministic rule set hash was fc87f4f0a74bc789dbe4ba85893c2c96f55db62c22970be4e991288104291621.",
    "The deterministic triage label was high; before timing adjustment it was high.",
    "The triage label is uncalibrated metadata, not a validated review-priority finding.",
    "The patch satisfied these deterministic event-class predicates: outcome_edit_cooccurs_with_results_posting.",
    "The timing context for the from-version record was late_recruitment.",
    "The deterministic rules that fired were: adverse_event_group_change.",
    "The changed JSON Pointer paths were: /protocolSection/statusModule/statusVerifiedDate, /protocolSection/statusModule/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/outcomesModule/primaryOutcomes/0/description, /protocolSection/outcomesModule/primaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/0/reviewUnit, /resultsSection/participantFlowModule/groups/0/description, /resultsSection/outcomeMeasuresModule/outcomeMeasures/0/description, /resultsSection/outcomeMeasuresModule/outcomeMeasures/0/timeFrame, /resultsSection/outcomeMeasuresModule/outcomeMeasures/0/reviewUnit, /resultsSection/adverseEventsModule/eventGroups/0/deathsNumAffected, /resultsSection/adverseEventsModule/allCauseMortalityReviewUnit, /annotationSection/annotationModule/unpostedAnnotation/unpostedEvents/0/date, /reviewUnit.",
    "An outcome path changed between versions 20 and 21 in a patch that also carried a hasResults or resultsSection co-occurrence signal."
  ],
  "classification": {
    "calibration_status": "uncalibrated",
    "categories": [
      "adverse_event_group_change",
      "results_reconciliation"
    ],
    "category": "adverse_event_group_change",
    "deterministic_rules": [
      "adverse_event_group_change"
    ],
    "event_class_rule_set_hash": "74a6f55a686c29aa023171acd6b43f27ea95f2b0af2d49094ac70287ba4e502c",
    "event_classes": [
      "outcome_edit_cooccurs_with_results_posting"
    ],
    "rule_set_hash": "fc87f4f0a74bc789dbe4ba85893c2c96f55db62c22970be4e991288104291621",
    "severity": "high",
    "severity_pre_timing": "high",
    "timing_context": "late_recruitment",
    "triage_label": "high",
    "triage_rule_set_hash": "af5e5835e00a5fcfe2a17fd02b5fc244c2564104f93f78a1d77d7889f12a178b",
    "value_signals": [
      {
        "category": "results_reconciliation",
        "paths": [
          "/protocolSection/outcomesModule/primaryOutcomes/0/description",
          "/protocolSection/outcomesModule/primaryOutcomes/0/reviewUnit",
          "/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame"
        ],
        "severity": "low",
        "signal": "results_reconciliation_outcome_suppression"
      }
    ]
  },
  "event_id": "evt_NCT03025035_v20_v21_277ca9725ed5",
  "evidence_version": 1,
  "patch": [
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/statusVerifiedDate",
      "value": "2025-05"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdateSubmitDate",
      "value": "2025-05-08"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
      "value": "2025-05-23"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/primaryOutcomes/0/description",
      "value": "Defined as complete or partial response or stable disease per RECIST 1.1 criteria with assessment every 9 weeks during the first year and while on the study drug, and every 12 weeks thereafter.\nPer Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), a tumor that is neither shrinking sufficiently to be considered a partial response (PR) (at least 30% decrease in tumor burden), nor growing significantly enough to be considered progressive disease (PD) (more than 20% increase in tumor burden); Overall Response (OR) = CR + PR + SD"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
      "value": "until all patients off study"
    },
    {
      "op": "add",
      "path": "/protocolSection/outcomesModule/primaryOutcomes/0/reviewUnit",
      "value": {
        "resetReasons": [
          "There does not appear to be sufficient information to understand the Time Frame."
        ]
      }
    },
    {
      "op": "replace",
      "path": "/resultsSection/participantFlowModule/groups/0/description",
      "value": "<p>This is an open-label, single-arm pilot study of pembrolizumab (study drug) in combination with Olaparib in 20 subjects with advanced BRCA mutation and&#x2F;or HDR-defect associated breast cancer having progressed through at least a standard first line therapy.</p><p>Pembrolizumab: Pembrolizumab IV solution administered on Day 1 of each 3-week cycle</p><p>Olaparib: Olaparib administered orally twice a day</p>"
    },
    {
      "op": "replace",
      "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/0/description",
      "value": "Defined as complete or partial response or stable disease per RECIST 1.1 criteria with assessment every 9 weeks during the first year and while on the study drug, and every 12 weeks thereafter.\nPer Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), a tumor that is neither shrinking sufficiently to be considered a partial response (PR) (at least 30% decrease in tumor burden), nor growing significantly enough to be considered progressive disease (PD) (more than 20% increase in tumor burden); Overall Response (OR) = CR + PR + SD"
    },
    {
      "op": "replace",
      "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/0/timeFrame",
      "value": "until all patients off study"
    },
    {
      "op": "add",
      "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/0/reviewUnit",
      "value": {
        "resetReasons": [
          "There does not appear to be sufficient information to understand the Time Frame."
        ]
      }
    },
    {
      "op": "replace",
      "path": "/resultsSection/adverseEventsModule/eventGroups/0/deathsNumAffected",
      "value": 6
    },
    {
      "op": "remove",
      "path": "/resultsSection/adverseEventsModule/allCauseMortalityReviewUnit"
    },
    {
      "op": "replace",
      "path": "/annotationSection/annotationModule/unpostedAnnotation/unpostedEvents/0/date",
      "value": "2025-05-22"
    },
    {
      "op": "add",
      "path": "/reviewUnit",
      "value": {
        "resetReasons": [
          "This record has new issues that must be addressed."
        ]
      }
    }
  ],
  "provenance": {
    "from_snapshot_hash": "17c518b5db5b4c88066f59a66a3987882985e29795e31da500724064e08e2fd9",
    "materiality_event_hash": "149929c847df964cc389172793defd374552d1933ba5cf28a050f1016f424d39",
    "patch_hash": "d4561d4b724a3304f5a3f34d9a6b7bbba44033ddb18f419e562e385f0e1205a8",
    "patch_raw_hash": "413a4dab1b26fa615c68406b615c449be657226f4b4e0ac5cf71948488218ee6",
    "patch_source": "ctgov_internal_history",
    "patch_source_url": "https://clinicaltrials.gov/api/int/studies/NCT03025035/history/20?patchToVersion=21",
    "to_snapshot_hash": "9cc52e41cc66d07a05e822a084883cf472757b8259f061a9ff81f4291d269679"
  },
  "review_question": "What source document explains this registry amendment, and does it change interpretation of the trial record?",
  "schema": "trialdiff.evidence_record",
  "trial": {
    "clinicaltrials_gov_url": "https://clinicaltrials.gov/study/NCT03025035",
    "nct_id": "NCT03025035"
  },
  "versions": {
    "from_version": 20,
    "submitted_date": "2025-05-08",
    "to_version": 21
  }
}