Table 3 Study definitions

Bronchopulmonary hemorrhage

 A disorder characterized by bleeding from the bronchial wall and/or lung parenchyma. Degree of severity will be classified according to Common Terminology Criteria for Adverse Events (CTCAE) grade [38].The incidence of bronchopulmonary hemorrhage related to ENB index procedure rated as Grade 2 or higher according to CTCAE scale will be captured and reported:

  • Grade 2: Moderate symptoms; medical intervention indicated

  • Grade 3: Transfusion, radiologic, endoscopic, or operative intervention indicated (e.g., hemostasis of bleeding site)

  • Grade 4: Life-threatening respiratory or hemodynamic compromise; intubation or urgent intervention indicated

  • Grade 5: Death

 Bronchopulmonary hemorrhage will also be reported based on a newly validated airway bleeding scale (E. Folch and S. Khandhar, unpublished personal communication; publication in progress).

Diagnostic yield

 Diagnostic yield of the ENB procedure will be calculated on a per-subject basis out of all subjects in whom a diagnostic biopsy is attempted and is defined as the proportion of subjects in whom the ENB procedure yielded a definitive diagnosis. Accuracy of all diagnoses aided by the ENB procedure, as well as nondiagnostic cases, will evaluated based on 2-year clinical follow-up (see below).

Diagnostic accuracy

 Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) will be calculated as the accuracy of the ENB-aided diagnosis (based on final pathology results) compared to the final 2-year diagnosis based on all available procedures and follow-up.

 Where a = true positive, b = false positive, c = false negative, and d = true negative:

  • Sensitivity: Probability that an ENB-guided biopsy will be positive when malignancy is present (true positive rate): = a/(a + c)

  • Specificity: Probability that an ENB-guided biopsy will be negative when malignancy is not present (true negative rate): = d/(b + d)

  • PPV: Probability that malignancy is present when an ENB-guided biopsy is positive: = a/(a + b)

  • NPV: Probability that malignancy is not present when an ENB-guided biopsy is negative: = d/(c + d)

Lesion size

 Defined as greatest diameter of the target lesion.

Navigation Accuracy

 Distance between the tip of the locatable guide and the targeted lung lesion (not done for lymph nodes).

Navigation success

 The proportion of cases in which the operator is able to successfully navigate to the lung target with ENB guidance, based on investigator self-assessment.

Navigation time

 Total time that the locatable guide is used in the subject during the ENB procedure.

Peripheral lung lesion

 A lesion that is located in the outer third of the lung and difficult to reach by traditional bronchoscopy (see Additional file 3, Peripheral Lung Lesion Definition).

Pneumothorax

 A disorder characterized by abnormal presence of air in the pleural cavity resulting in the collapse of the lung. The primary endpoint is the incidence of pneumothorax related to the ENB index procedure rated as Grade 2 or higher. All grades will be captured as a secondary endpoint. Degree of severity will be classified according to CTCAE grade as follows:

  • Grade 1: Asymptomatic; clinical or diagnostic observations only; intervention not indicated.

  • Grade 2: Symptomatic; intervention indicated (e.g., tube placement without sclerosis).

  • Grade 3: Sclerosis and/or operative intervention indicated; hospitalization indicated.

  • Grade 4: Life-threatening consequences; urgent intervention indicated.

  • Grade 5: Death.

 Pneumothorax severity will also be reported based on a newly validated scale that takes into account variance in international standard of care for observation and intervention following asymptomatic pneumothorax and compared to the CTCAE criteria.

Procedure time

 Time between initial introduction of the locatable guide into the body and final removal of the locatable guide.

Repeat biopsy

 Additional biopsy or biopsies conducted after the ENB-guided index procedure, required due to insufficient tissue collection for diagnosis at the index procedure.

Respiratory failure

 A disorder characterized by impaired gas exchange by the respiratory system resulting in hypoxemia and a decrease in oxygenation of the tissues that may be associated with an increase in arterial levels of carbon dioxide. Degree of severity will be classified according to CTCAE grade as follows:

  • Grade 4: Life-threatening consequences; urgent intervention, intubation, or ventilatory support indicated.

  • Grade 5: Death.

Stage

 Lung cancer staging will be defined according to the Revised International System for Staging Lung Cancer (TNM) Classification System.

Tissue adequacy

 Tissue adequacy is defined as the proportion of cases in which tissue obtained during the ENB index procedure is adequate for subtyping of lung cancer and molecular testing when appropriate