evt_NCT03414684_v17_v18_affb2afae675

{
  "changed_paths": [
    "/protocolSection/statusModule/statusVerifiedDate",
    "/protocolSection/statusModule/lastUpdateSubmitDate",
    "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
    "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
    "/protocolSection/outcomesModule/primaryOutcomes/0/description",
    "/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/0/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/2/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/3/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/3/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/4/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/5/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/5/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/6/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/6/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/7/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/7/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/7/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/8"
  ],
  "citation_text": "TrialDiff Evidence Record evt_NCT03414684_v17_v18_affb2afae675. ClinicalTrials.gov NCT03414684, versions 17-18. 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 the outcome change was inconsistent with the protocol or statistical analysis plan.",
    "That event-class membership is a validated global review-priority ranking."
  ],
  "claims_supported": [
    "TrialDiff compared ClinicalTrials.gov record version 17 to version 18 for NCT03414684.",
    "The JSON Patch for this comparison has hash d50f38888f0f0abc4c465ed8d20ea76462a9a7761e5c88f28d25762cf588490e.",
    "The active deterministic rule set hash was fc87f4f0a74bc789dbe4ba85893c2c96f55db62c22970be4e991288104291621.",
    "The deterministic triage label was critical; before timing adjustment it was critical.",
    "The triage label is uncalibrated metadata, not a validated review-priority finding.",
    "The patch satisfied these deterministic event-class predicates: primary_endpoint_changed_after_primary_completion_without_results_reconciliation.",
    "A registry field under the primary outcome module changed between ClinicalTrials.gov versions 17 and 18.",
    "The timing context for the from-version record was late_recruitment.",
    "The deterministic rules that fired were: primary_outcome_any_change, secondary_outcome_any_change.",
    "The changed JSON Pointer paths were: /protocolSection/statusModule/statusVerifiedDate, /protocolSection/statusModule/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/outcomesModule/primaryOutcomes/0/measure, /protocolSection/outcomesModule/primaryOutcomes/0/description, /protocolSection/outcomesModule/primaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/0/measure, /protocolSection/outcomesModule/secondaryOutcomes/0/description, /protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/1/measure, /protocolSection/outcomesModule/secondaryOutcomes/1/description, /protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/2/measure, /protocolSection/outcomesModule/secondaryOutcomes/2/description, /protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/3/measure, /protocolSection/outcomesModule/secondaryOutcomes/3/description, /protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/4/measure, /protocolSection/outcomesModule/secondaryOutcomes/4/description, /protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/5/measure, /protocolSection/outcomesModule/secondaryOutcomes/5/description, /protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/6/measure, /protocolSection/outcomesModule/secondaryOutcomes/6/description, /protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/7/measure, /protocolSection/outcomesModule/secondaryOutcomes/7/description, /protocolSection/outcomesModule/secondaryOutcomes/7/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/8.",
    "A primary outcome definition field changed after primary completion between versions 17 and 18, without a results-posting co-occurrence signal."
  ],
  "classification": {
    "calibration_status": "uncalibrated",
    "categories": [
      "primary_outcome_change",
      "secondary_outcome_change"
    ],
    "category": "primary_outcome_change",
    "deterministic_rules": [
      "primary_outcome_any_change",
      "secondary_outcome_any_change"
    ],
    "event_class_rule_set_hash": "74a6f55a686c29aa023171acd6b43f27ea95f2b0af2d49094ac70287ba4e502c",
    "event_classes": [
      "primary_endpoint_changed_after_primary_completion_without_results_reconciliation"
    ],
    "rule_set_hash": "fc87f4f0a74bc789dbe4ba85893c2c96f55db62c22970be4e991288104291621",
    "severity": "critical",
    "severity_pre_timing": "critical",
    "timing_context": "late_recruitment",
    "triage_label": "critical",
    "triage_rule_set_hash": "af5e5835e00a5fcfe2a17fd02b5fc244c2564104f93f78a1d77d7889f12a178b",
    "value_signals": []
  },
  "event_id": "evt_NCT03414684_v17_v18_affb2afae675",
  "evidence_version": 1,
  "patch": [
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/statusVerifiedDate",
      "value": "2022-10"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdateSubmitDate",
      "value": "2022-10-03"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
      "value": "2022-10-05"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
      "value": "Progression-free survival"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/primaryOutcomes/0/description",
      "value": "Defined as the time from randomization (or registration) to the earlier of progression or death due to any cause.\nParticipants alive without disease progression are censored at date of last disease evaluation"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
      "value": "3.5 years"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
      "value": "Objective response rate by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/0/description",
      "value": "Defined as the proportion of patients achieving a complete response (complete disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits [i.e., "non-CR/non-PD" in non-target lesions]; and no new lesions) based on RECIST 1.1"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
      "value": "3.5 years"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
      "value": "Objective response rate by Immune-Related Response Criteria (irRC)"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
      "value": "Defined as the proportion of patients achieving an immune-related complete response (complete disappearance of all target and non-target lesions; no new measurable/unmeasurable lesions) or immune-related partial response (a decrease of the immune-related sum of product diameters [irSPD] of 50% or greater) based on irRC"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
      "value": "3.5 years"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
      "value": "Overall survival"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/description",
      "value": "Defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
      "value": "3.5 years"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/3/measure",
      "value": "Clinical benefit rate"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/3/description",
      "value": "Defined as the proportion of patients achieving a complete response or partial response by RECIST 1.1, or stable disease lasting greater than or equal to 24 weeks"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
      "value": "3.5 years"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
      "value": "Duration of response"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/4/description",
      "value": "Defined as the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.\nPatients without events reported are censored at the last disease evaluation"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
      "value": "3.5 years"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/5/measure",
      "value": "Time to objective response"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/5/description",
      "value": "Defined as the time from registration to the date of the first documented CR or PR by RECIST 1.1, whichever is first recorded"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame",
      "value": "3.5 years"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/6/measure",
      "value": "Efficacy among PD-L1-positive patients"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/6/description",
      "value": "PFS, ORR according to RECIST 1.1 and irRC, CBR, DOR, TTOR and OS, among patients with PD-L1-positive disease, defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1 (all efficacy endpoints defined as above in outcomes 1-7)"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame",
      "value": "3.5 years"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/7/measure",
      "value": "Efficacy among BRCA-mutant patients"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/7/description",
      "value": "PFS, ORR according to RECIST 1.1 and irRC, CBR, DOR, TTOR and OS, among patients with germline BRCA1 or BRCA2 mutations (all efficacy endpoints defined as above in outcomes 1-7)"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/7/timeFrame",
      "value": "3.5 years"
    },
    {
      "op": "add",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/8",
      "value": {
        "description": "PFS, ORR according to RECIST 1.1 and irRC, CBR, DOR, TTOR and OS among patients who crossover to receive nab-paclitaxel + nivolumab + carboplatin after progression on carboplatin alone (all efficacy endpoints defined as above in outcomes 1-7)",
        "measure": "Efficacy of nab-paclitaxel during second-course therapy, among crossover patients",
        "timeFrame": "3.5 years"
      }
    }
  ],
  "provenance": {
    "from_snapshot_hash": "c35dff4bbd0613741ea0c72e61678ec988dcaf23754b43afdc389e2348010a38",
    "materiality_event_hash": "1e5700c9e61ca7fd94734ece6dd1395c273d88c7e25b86f71a490585795d2e5c",
    "patch_hash": "d50f38888f0f0abc4c465ed8d20ea76462a9a7761e5c88f28d25762cf588490e",
    "patch_raw_hash": "a923c8d0708cf63110457801dbbcf184629bc55b1a76f918e915cf0f8115855a",
    "patch_source": "ctgov_internal_history",
    "patch_source_url": "https://clinicaltrials.gov/api/int/studies/NCT03414684/history/17?patchToVersion=18",
    "to_snapshot_hash": "9fa55a73afa002e423d266b3f6067fb920b17b4fdc15609d85b43b2a75daf45a"
  },
  "review_question": "What did the primary outcome field say before and after the amendment, and is there a public protocol, statistical analysis plan, or manuscript explaining the change?",
  "schema": "trialdiff.evidence_record",
  "trial": {
    "clinicaltrials_gov_url": "https://clinicaltrials.gov/study/NCT03414684",
    "nct_id": "NCT03414684"
  },
  "versions": {
    "from_version": 17,
    "submitted_date": "2022-10-03",
    "to_version": 18
  }
}