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      ]
    },
    {
      "annotation_id": "annot-007",
      "table_id": "table-001",
      "annotation_marker": "f",
      "annotation_type": "footnote",
      "annotation_text": "For women of childbearing potential, including those who have had a tubal ligation, positive urine test results will be confirmed with a serum pregnancy test. Study drug infusion must not be administered unless the serum pregnancy test result is negative.",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-011"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 14
        }
      ]
    },
    {
      "annotation_id": "annot-008",
      "table_id": "table-001",
      "annotation_marker": "g",
      "annotation_type": "footnote",
      "annotation_text": "If arterial blood gases are measured.",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-012"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 15
        }
      ]
    },
    {
      "annotation_id": "annot-009",
      "table_id": "table-001",
      "annotation_marker": "h",
      "annotation_type": "footnote",
      "annotation_text": "All vital sign measurements (i.e., respiratory rate, pulse rate, systolic and diastolic blood pressures, and body temperature), oxygen saturation and NEWS2-specific assessments (i.e., consciousness and presence or absence of oxygen support) should be recorded together twice daily with approximately 12 hours in between while the patient remains hospitalized. If measured more than once during a 12-hour period, the worst values (highest temperature, respiratory rate, and heart rate; lowest blood pressure, oxygen saturation, and consciousness level) during that period should be recorded on the eCRF.",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-013",
          "act-014"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 16
        },
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 17
        }
      ]
    },
    {
      "annotation_id": "annot-010",
      "table_id": "table-001",
      "annotation_marker": "i",
      "annotation_type": "footnote",
      "annotation_text": "Assessment of clinical status using the ordinal scale should be recorded at baseline on Day 1/Visit 1 then again daily every morning (between 8 am and 12 pm) for patients who remain hospitalized.",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-015"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 18
        }
      ]
    },
    {
      "annotation_id": "annot-011",
      "table_id": "table-001",
      "annotation_marker": "j",
      "annotation_type": "footnote",
      "annotation_text": "After informed consent has been obtained but prior to initiation of study drug, only serious adverse events caused by a protocol-mandated intervention should be reported. After initiation of study drug, all adverse events will be reported until 60 days after the final dose of study drug. After this period, the Sponsor should be notified if the investigator becomes aware of any serious adverse event that is believed to be related to prior study drug treatment (see Section 5.6).",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-016"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 19
        }
      ],
      "document_references": [
        {
          "kind": "section",
          "target": "5.6"
        }
      ]
    },
    {
      "annotation_id": "annot-012",
      "table_id": "table-001",
      "annotation_marker": "k",
      "annotation_type": "footnote",
      "annotation_text": "Medication (e.g., prescription drugs, over-the-counter drugs, vaccines, herbal or homeopathic remedies, nutritional supplements) used by a patient in addition to protocol-mandated treatment from 7 days prior to initiation of study drug to the study completion/discontinuation visit.",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-017"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 20
        }
      ]
    },
    {
      "annotation_id": "annot-013",
      "table_id": "table-001",
      "annotation_marker": "l",
      "annotation_type": "footnote",
      "annotation_text": "Hematology includes WBC count, RBC count, hemoglobin, hematocrit, platelet count, differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes), and lymphocyte subsets (T cells, B cells, and NK cells; if the test is available at the site).",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-018"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 21
        }
      ]
    },
    {
      "annotation_id": "annot-014",
      "table_id": "table-001",
      "annotation_marker": "m",
      "annotation_type": "footnote",
      "annotation_text": "Chemistry panel (serum or plasma) includes bicarbonate or total carbon dioxide (if considered standard of care for the region), sodium, potassium, chloride, glucose, BUN or urea, creatinine, total protein, albumin, phosphorus, calcium, total bilirubin, ALP, ALT, and/or AST, uric acid, LDH, ferritin, and D-dimer.",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-019"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 22
        }
      ]
    },
    {
      "annotation_id": "annot-015",
      "table_id": "table-001",
      "annotation_marker": "n",
      "annotation_type": "footnote",
      "annotation_text": "Study drug should be administered after collection of all samples for pharmacodynamic and exploratory biomarker analyses. The initial study drug infusion should be given within 4 hours of randomization. If the clinical signs or symptoms worsen or do not improve (reflected by sustained fever or at least a one-category worsening on the 7-category ordinal scale of clinical status), one additional infusion of blinded treatment of TCZ or placebo can be given, 8–24 hours after the initial infusion.",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-020"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 23
        }
      ]
    },
    {
      "annotation_id": "annot-016",
      "table_id": "table-001",
      "annotation_marker": "o",
      "annotation_type": "footnote",
      "annotation_text": "On Day 1, CRP, IL-6, and sIL-6R samples should be drawn 0–4 hours before the start of infusion and then within 15 minutes (to 1 hour) after the end of the infusion, on the opposite arm as the infusion. Patents receiving a second infusion of study drug should provide extra samples for CRP, IL-6, and sIL-6R prior to and 15 minutes after the end of the infusion, on the opposite arm as the infusion.",
      "annotation_scope": "cell",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [],
        "cell_references": [
          {
            "activity_id": "act-022",
            "column_id": "col-003"
          },
          {
            "activity_id": "act-022",
            "column_id": "col-004"
          }
        ]
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "schedule_cell",
          "row_position": 25,
          "column_position": 3
        },
        {
          "table_number": 1,
          "location_type": "schedule_cell",
          "row_position": 25,
          "column_position": 4
        }
      ]
    },
    {
      "annotation_id": "annot-017",
      "table_id": "table-001",
      "annotation_marker": "p",
      "annotation_type": "footnote",
      "annotation_text": "Patents receiving a second infusion of study drug should provide an extra PK sample prior to and 15 minutes (to 1 hour) after the end of the infusion, on the opposite arm as the infusion.",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-023"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 26
        }
      ]
    },
    {
      "annotation_id": "annot-018",
      "table_id": "table-001",
      "annotation_marker": "q",
      "annotation_type": "footnote",
      "annotation_text": "On Day 1, PK samples should be drawn 0–4 hours before the start of infusion and then within 15 minutes (to 1 hour) after the end of the infusion, on the opposite arm as the infusion.",
      "annotation_scope": "cell",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [],
        "cell_references": [
          {
            "activity_id": "act-023",
            "column_id": "col-003"
          },
          {
            "activity_id": "act-023",
            "column_id": "col-004"
          }
        ]
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "schedule_cell",
          "row_position": 26,
          "column_position": 3
        },
        {
          "table_number": 1,
          "location_type": "schedule_cell",
          "row_position": 26,
          "column_position": 4
        }
      ]
    },
    {
      "annotation_id": "annot-019",
      "table_id": "table-001",
      "annotation_marker": "r",
      "annotation_type": "footnote",
      "annotation_text": "Viral load will be assessed by nasopharyngeal swab. Patients who are intubated and undergo bronchoalveolar lavage will have samples taken for virological assessment. It may only be possible to access one nostril if a patient has a nasogastric tube in place, in which case sites may collect a sample from one nostril only and where possible the same nostril should be used.",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-025"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 28
        }
      ]
    },
    {
      "annotation_id": "annot-020",
      "table_id": "table-001",
      "annotation_marker": "s",
      "annotation_type": "footnote",
      "annotation_text": "For sites capable of sample collection for analysis of T cells by high-dimensional cytometry.",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-027"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 30
        }
      ]
    },
    {
      "annotation_id": "annot-021",
      "table_id": "table-001",
      "annotation_marker": "t",
      "annotation_type": "footnote",
      "annotation_text": "The first draw of blood should not be for PAXgene® tubes to avoid contact with RNA preservation reagent inside the tube.",
      "annotation_scope": "activity",
      "referenced_elements": {
        "property_ids": [],
        "column_ids": [],
        "activity_ids": [
          "act-028"
        ],
        "cell_references": []
      },
      "marker_locations": [
        {
          "table_number": 1,
          "location_type": "activity_name",
          "row_position": 31
        }
      ]
    }
  ],
  "review_items": [
    {
      "id": "D1",
      "severity": "medium",
      "location": {
        "page": 78,
        "row_positions": [
          25,
          26,
          27,
          28,
          29,
          30,
          31
        ]
      },
      "call_made": "In all three tables the rows printed below the bold/underlined 'Central Labs' header row (to the end of the table) are recorded as children of that header (indentation level 1); every other row is top level (0). The source prints no visual indent.",
      "alternative": "Treat the table as flat: all rows at level 0, with 'Central Labs' as a mark-free level-0 row that does not group the rows beneath it.",
      "report_section": "4.1"
    },
    {
      "id": "D2",
      "severity": "high",
      "location": {
        "page": 77,
        "row_position": 15
      },
      "call_made": "The PaO2/FiO2 cell '← Optional →' drawn across the merged Day 1-Day 2 columns is distributed as the value '← Optional →' on each covered column (Table 1 columns 3-6; Table 2 columns 2-27, plus a separate 'Optional' at column 28).",
      "alternative": "Treat 'Optional' as a condition on the activity (a note) rather than as a scheduled value in each column, leaving those cells unscheduled.",
      "report_section": "4.2"
    },
    {
      "id": "D3",
      "severity": "medium",
      "location": {
        "page": 77,
        "row_position": 1
      },
      "call_made": "The top header band ('Screening' | 'Baseline' | blank over columns 4-6) is typed epoch, with a synthesized name 'Study Period'; the blank merged cell over the Day 1 post-dose and Day 2 columns is left empty.",
      "alternative": "Type the band as visit ('Baseline' is a visit name), or treat the blank span as an unlabelled treatment epoch.",
      "report_section": "4.3"
    }
  ]
}