evt_NCT03734029_v29_v30_9a48cca0a885

{
  "changed_paths": [
    "/protocolSection/statusModule/statusVerifiedDate",
    "/protocolSection/statusModule/completionDateStruct/date",
    "/protocolSection/statusModule/lastUpdateSubmitDate",
    "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
    "/protocolSection/statusModule/resultsFirstSubmitQcDate",
    "/protocolSection/statusModule/resultsFirstPostDateStruct",
    "/protocolSection/outcomesModule/secondaryOutcomes/1",
    "/protocolSection/outcomesModule/secondaryOutcomes/1",
    "/protocolSection/outcomesModule/secondaryOutcomes/3",
    "/protocolSection/outcomesModule/secondaryOutcomes/4",
    "/protocolSection/outcomesModule/secondaryOutcomes/5",
    "/protocolSection/outcomesModule/otherOutcomes",
    "/resultsSection/participantFlowModule/periods/0/milestones/1",
    "/resultsSection/participantFlowModule/periods/0/milestones/2",
    "/resultsSection/outcomeMeasuresModule/outcomeMeasures/2",
    "/resultsSection/outcomeMeasuresModule/outcomeMeasures/2",
    "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4",
    "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5",
    "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6",
    "/resultsSection/outcomeMeasuresModule/outcomeMeasures/11",
    "/resultsSection/adverseEventsModule/timeFrame",
    "/resultsSection/adverseEventsModule/description",
    "/resultsSection/adverseEventsModule/eventGroups/0/deathsNumAffected",
    "/resultsSection/adverseEventsModule/eventGroups/0/deathsNumAtRisk",
    "/resultsSection/adverseEventsModule/eventGroups/1/deathsNumAffected",
    "/resultsSection/adverseEventsModule/eventGroups/1/deathsNumAtRisk",
    "/resultsSection/adverseEventsModule/armsReviewUnit",
    "/resultsSection/adverseEventsModule/allCauseMortalityReviewUnit",
    "/annotationSection",
    "/reviewUnit"
  ],
  "citation_text": "TrialDiff Evidence Record evt_NCT03734029_v29_v30_9a48cca0a885. ClinicalTrials.gov NCT03734029, versions 29-30. 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 29 to version 30 for NCT03734029.",
    "The JSON Patch for this comparison has hash 857ff437dce10fafb759508bac550e4a5ce82eb5bec9274441aa707a2084c797.",
    "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, secondary_outcome_removed_after_primary_completion.",
    "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/completionDateStruct/date, /protocolSection/statusModule/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/statusModule/resultsFirstSubmitQcDate, /protocolSection/statusModule/resultsFirstPostDateStruct, /protocolSection/outcomesModule/secondaryOutcomes/1, /protocolSection/outcomesModule/secondaryOutcomes/1, /protocolSection/outcomesModule/secondaryOutcomes/3, /protocolSection/outcomesModule/secondaryOutcomes/4, /protocolSection/outcomesModule/secondaryOutcomes/5, /protocolSection/outcomesModule/otherOutcomes, /resultsSection/participantFlowModule/periods/0/milestones/1, /resultsSection/participantFlowModule/periods/0/milestones/2, /resultsSection/outcomeMeasuresModule/outcomeMeasures/2, /resultsSection/outcomeMeasuresModule/outcomeMeasures/2, /resultsSection/outcomeMeasuresModule/outcomeMeasures/4, /resultsSection/outcomeMeasuresModule/outcomeMeasures/5, /resultsSection/outcomeMeasuresModule/outcomeMeasures/6, /resultsSection/outcomeMeasuresModule/outcomeMeasures/11, /resultsSection/adverseEventsModule/timeFrame, /resultsSection/adverseEventsModule/description, /resultsSection/adverseEventsModule/eventGroups/0/deathsNumAffected, /resultsSection/adverseEventsModule/eventGroups/0/deathsNumAtRisk, /resultsSection/adverseEventsModule/eventGroups/1/deathsNumAffected, /resultsSection/adverseEventsModule/eventGroups/1/deathsNumAtRisk, /resultsSection/adverseEventsModule/armsReviewUnit, /resultsSection/adverseEventsModule/allCauseMortalityReviewUnit, /annotationSection, /reviewUnit.",
    "The timeline value moved by 366 days.",
    "An outcome path changed between versions 29 and 30 in a patch that also carried a hasResults or resultsSection co-occurrence signal.",
    "The JSON Patch removed a whole secondary outcome item after primary completion between versions 29 and 30; when a TO-version outcome list is available, reindex-only removals are excluded."
  ],
  "classification": {
    "calibration_status": "uncalibrated",
    "categories": [
      "adverse_event_group_change",
      "timeline_major_slip",
      "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",
      "secondary_outcome_removed_after_primary_completion"
    ],
    "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": "timeline_major_slip",
        "date_struct": "completionDateStruct",
        "delta_days": 366,
        "direction": "later",
        "new_precision": "month",
        "new_type": "ESTIMATED",
        "new_value": "2024-03",
        "old_precision": "month",
        "old_type": "ESTIMATED",
        "old_value": "2023-03",
        "path": "/protocolSection/statusModule/completionDateStruct/date",
        "severity": "high",
        "signal": "timeline_major_slip"
      },
      {
        "category": "results_reconciliation",
        "paths": [
          "/protocolSection/outcomesModule/secondaryOutcomes/1",
          "/protocolSection/outcomesModule/secondaryOutcomes/3",
          "/protocolSection/outcomesModule/secondaryOutcomes/4",
          "/protocolSection/outcomesModule/secondaryOutcomes/5"
        ],
        "severity": "low",
        "signal": "results_reconciliation_outcome_suppression"
      }
    ]
  },
  "event_id": "evt_NCT03734029_v29_v30_9a48cca0a885",
  "evidence_version": 1,
  "patch": [
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/statusVerifiedDate",
      "value": "2023-05"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/completionDateStruct/date",
      "value": "2024-03"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdateSubmitDate",
      "value": "2023-05-25"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
      "value": "2023-06-15"
    },
    {
      "op": "add",
      "path": "/protocolSection/statusModule/resultsFirstSubmitQcDate",
      "value": "2023-05-25"
    },
    {
      "op": "add",
      "path": "/protocolSection/statusModule/resultsFirstPostDateStruct",
      "value": {
        "date": "2023-06-15",
        "type": "ACTUAL"
      }
    },
    {
      "op": "remove",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1"
    },
    {
      "op": "remove",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1"
    },
    {
      "op": "add",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/3",
      "value": {
        "description": "Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause.\nIf there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.",
        "measure": "Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer",
        "timeFrame": "From the date of randomization up to the date of death due to any cause, up to approximately 3 years"
      }
    },
    {
      "op": "add",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/4",
      "value": {
        "measure": "Number of Overall Survival Events (Deaths)",
        "timeFrame": "From the date of randomization up to the date of death due to any cause, up to approximately 3 years"
      }
    },
    {
      "op": "add",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/5",
      "value": {
        "description": "Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause.\nIf there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.",
        "measure": "Overall Survival (OS) in All Patients",
        "timeFrame": "From the date of randomization up to the date of death due to any cause, up to approximately 3 years"
      }
    },
    {
      "op": "add",
      "path": "/protocolSection/outcomesModule/otherOutcomes",
      "value": [
        {
          "description": "All-cause mortality is defined as all anticipated and unanticipated deaths due to any cause, with the number and frequency of such events by arm or comparison group of the clinical study.",
          "measure": "All-Cause Mortality",
          "timeFrame": "From the date of randomization up to the date of death due to any cause, up to approximately 3 years"
        }
      ]
    },
    {
      "op": "add",
      "path": "/resultsSection/participantFlowModule/periods/0/milestones/1",
      "value": {
        "achievements": [
          {
            "groupId": "FG000",
            "numSubjects": "373"
          },
          {
            "groupId": "FG001",
            "numSubjects": "184"
          }
        ],
        "type": "Full Analysis Set (All Randomized Patients)"
      }
    },
    {
      "op": "add",
      "path": "/resultsSection/participantFlowModule/periods/0/milestones/2",
      "value": {
        "achievements": [
          {
            "groupId": "FG000",
            "numSubjects": "371"
          },
          {
            "groupId": "FG001",
            "numSubjects": "172"
          }
        ],
        "type": "Safety Analysis Set (All Randomized Patients Who Received at Least 1 Dose of Study Treatment)"
      }
    },
    {
      "op": "remove",
      "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/2"
    },
    {
      "op": "remove",
      "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/2"
    },
    {
      "op": "add",
      "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/4",
      "value": {
        "classes": [
          {
            "categories": [
              {
                "measurements": [
                  {
                    "groupId": "OG000",
                    "lowerLimit": "20.8",
                    "upperLimit": "24.8",
                    "value": "23.9"
                  },
                  {
                    "groupId": "OG001",
                    "lowerLimit": "15.2",
                    "upperLimit": "22.4",
                    "value": "17.5"
                  }
                ]
              }
            ]
          }
        ],
        "denoms": [
          {
            "counts": [
              {
                "groupId": "OG000",
                "value": "331"
              },
              {
                "groupId": "OG001",
                "value": "163"
              }
            ],
            "units": "Participants"
          }
        ],
        "description": "Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause.\nIf there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.",
        "dispersionType": "95% Confidence Interval",
        "groups": [
          {
            "description": "Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes.\nIf there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.",
            "id": "OG000",
            "title": "Trastuzumab Deruxtecan (T-DXd)"
          },
          {
            "description": "Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.",
            "id": "OG001",
            "title": "Physician's Choice"
          }
        ],
        "paramType": "MEDIAN",
        "populationDescription": "Overall survival (OS) was assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.",
        "reportingStatus": "POSTED",
        "timeFrame": "From the date of randomization up to the date of death due to any cause, up to approximately 3 years",
        "title": "Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer",
        "type": "SECONDARY",
        "unitOfMeasure": "months"
      }
    },
    {
      "op": "add",
      "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/5",
      "value": {
        "classes": [
          {
            "categories": [
              {
                "measurements": [
                  {
                    "groupId": "OG000",
                    "value": "149"
                  },
                  {
                    "groupId": "OG001",
                    "value": "90"
                  }
                ]
              }
            ]
          }
        ],
        "denoms": [
          {
            "counts": [
              {
                "groupId": "OG000",
                "value": "373"
              },
              {
                "groupId": "OG001",
                "value": "184"
              }
            ],
            "units": "Participants"
          }
        ],
        "groups": [
          {
            "description": "Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes.\nIf there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.",
            "id": "OG000",
            "title": "Trastuzumab Deruxtecan (T-DXd)"
          },
          {
            "description": "Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.",
            "id": "OG001",
            "title": "Physician's Choice"
          }
        ],
        "paramType": "NUMBER",
        "populationDescription": "Overall survival events (deaths) were analyzed in the Full Analysis Set (defined as all randomized participants).",
        "reportingStatus": "POSTED",
        "timeFrame": "From the date of randomization up to the date of death due to any cause, up to approximately 3 years",
        "title": "Number of Overall Survival Events (Deaths)",
        "type": "SECONDARY",
        "unitOfMeasure": "events (deaths)"
      }
    },
    {
      "op": "add",
      "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/6",
      "value": {
        "classes": [
          {
            "categories": [
              {
                "measurements": [
                  {
                    "groupId": "OG000",
                    "lowerLimit": "20.0",
                    "upperLimit": "24.8",
                    "value": "23.4"
                  },
                  {
                    "groupId": "OG001",
                    "lowerLimit": "14.5",
                    "upperLimit": "20.0",
                    "value": "16.8"
                  }
                ]
              }
            ]
          }
        ],
        "denoms": [
          {
            "counts": [
              {
                "groupId": "OG000",
                "value": "373"
              },
              {
                "groupId": "OG001",
                "value": "184"
              }
            ],
            "units": "Participants"
          }
        ],
        "description": "Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause.\nIf there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.",
        "dispersionType": "95% Confidence Interval",
        "groups": [
          {
            "description": "Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes.\nIf there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.",
            "id": "OG000",
            "title": "Trastuzumab Deruxtecan (T-DXd)"
          },
          {
            "description": "Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.",
            "id": "OG001",
            "title": "Physician's Choice"
          }
        ],
        "paramType": "MEDIAN",
        "populationDescription": "Overall survival (OS) was assessed in the Full Analysis Set (defined as all randomized participants).",
        "reportingStatus": "POSTED",
        "timeFrame": "From the date of randomization up to the date of death due to any cause, up to approximately 3 years",
        "title": "Overall Survival (OS) in All Patients",
        "type": "SECONDARY",
        "unitOfMeasure": "months"
      }
    },
    {
      "op": "add",
      "path": "/resultsSection/outcomeMeasuresModule/outcomeMeasures/11",
      "value": {
        "classes": [
          {
            "categories": [
              {
                "measurements": [
                  {
                    "groupId": "OG000",
                    "value": "148"
                  },
                  {
                    "groupId": "OG001",
                    "value": "88"
                  }
                ]
              }
            ]
          }
        ],
        "denoms": [
          {
            "counts": [
              {
                "groupId": "OG000",
                "value": "371"
              },
              {
                "groupId": "OG001",
                "value": "172"
              }
            ],
            "units": "Participants"
          }
        ],
        "description": "All-cause mortality is defined as all anticipated and unanticipated deaths due to any cause, with the number and frequency of such events by arm or comparison group of the clinical study.",
        "groups": [
          {
            "description": "Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes.\nIf there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.",
            "id": "OG000",
            "title": "Trastuzumab Deruxtecan (T-DXd)"
          },
          {
            "description": "Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.",
            "id": "OG001",
            "title": "Physician's Choice"
          }
        ],
        "paramType": "COUNT_OF_PARTICIPANTS",
        "populationDescription": "All-cause mortality was assessed in the Safety Analysis Set.",
        "reportingStatus": "POSTED",
        "timeFrame": "From the date of randomization up to the date of death due to any cause, up to approximately 3 years",
        "title": "All-Cause Mortality",
        "type": "OTHER_PRE_SPECIFIED",
        "unitOfMeasure": "Participants"
      }
    },
    {
      "op": "replace",
      "path": "/resultsSection/adverseEventsModule/timeFrame",
      "value": "Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set."
    },
    {
      "op": "replace",
      "path": "/resultsSection/adverseEventsModule/description",
      "value": "All-cause mortality was assessed in all participants who were randomized (Full Analysis Set).\nPlease refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set.\nOther AEs and SAEs were assessed in the Safety Analysis Set.\nThe Physician's Choice (PC) treatment was based on the label approved in each country.\nAs prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group."
    },
    {
      "op": "replace",
      "path": "/resultsSection/adverseEventsModule/eventGroups/0/deathsNumAffected",
      "value": 149
    },
    {
      "op": "replace",
      "path": "/resultsSection/adverseEventsModule/eventGroups/0/deathsNumAtRisk",
      "value": 373
    },
    {
      "op": "replace",
      "path": "/resultsSection/adverseEventsModule/eventGroups/1/deathsNumAffected",
      "value": 90
    },
    {
      "op": "replace",
      "path": "/resultsSection/adverseEventsModule/eventGroups/1/deathsNumAtRisk",
      "value": 184
    },
    {
      "op": "remove",
      "path": "/resultsSection/adverseEventsModule/armsReviewUnit"
    },
    {
      "op": "remove",
      "path": "/resultsSection/adverseEventsModule/allCauseMortalityReviewUnit"
    },
    {
      "op": "remove",
      "path": "/annotationSection"
    },
    {
      "op": "remove",
      "path": "/reviewUnit"
    }
  ],
  "provenance": {
    "from_snapshot_hash": "e2a30ad695d0324f3a2e400ab6af2a1454346505b0d7f475f8e56814d12cae8c",
    "materiality_event_hash": "6c0157028f31ecdde6b145a710291abf30d767580717520839e4503a33ba7ccf",
    "patch_hash": "857ff437dce10fafb759508bac550e4a5ce82eb5bec9274441aa707a2084c797",
    "patch_raw_hash": "108f01e9d79868cd8cf19eddd9e7f2c465e593e5840905e6d1fdbcabcef1822a",
    "patch_source": "ctgov_internal_history",
    "patch_source_url": "https://clinicaltrials.gov/api/int/studies/NCT03734029/history/29?patchToVersion=30",
    "to_snapshot_hash": "e0354115fd9d35ab6fd3c0bc978eaec24bf65f7c3efcc6c9c9d379f6450cfc63"
  },
  "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/NCT03734029",
    "nct_id": "NCT03734029"
  },
  "versions": {
    "from_version": 29,
    "submitted_date": "2023-05-25",
    "to_version": 30
  }
}