Table 1 Eligibility criteria for key question 1 on benefits and harms of screening for lung cancer with computed tomography

Population

Adults ≥ 18 years old and not suspected to have lung cancer

Specific populations of interest may include:

• Studies of people seeking care for symptoms of lung cancer or who are suspected of lung cancer

• Studies of people who have been previously diagnosed with lung cancer

• Studies of people younger than 18 years old

• Study population includes > 25% individuals with recent abnormal screening result

• Age

• Sex

• Smoking history (e.g., duration, pack-years)

• Race and ethnicity (e.g., First Nations, Inuit and Métis)

• Populations for which screening access and outcomes may be inequitable (e.g., LGBTQ + , low socioeconomic status, homeless)

Intervention

Computed tomography (CT), with or without any other lung cancer screening interventions (e.g., biomarkers)

The focus is on screening interventions involving CT but we will include new RCTs (published in 2015 or later) of other screening modalities. Screening modalities (i.e., chest X-ray) examined in the last review (chest X-ray) will only be included if new RCTs are found

Comparator

• No screening/placebo/minimally or non-active intervention (e.g., smoking cessation)

• An alternative screening strategy/protocol (e.g., use of risk-prediction model vs risk-factor based screening criteria, different screening interval or method to classify nodules)

• None (only for harm outcomes except overdiagnosis where a no screening arm is required)

Outcomes (by importance as rated by the WG)

Benefits:

1. All-cause mortality*

2. Lung cancer mortality*

3. Health-related quality of life

If there is trial evidence showing at least low certainty of benefit for 1 + of the above outcomes, then:

Harms:

4. Overdiagnosis of lung cancer*

5. Major complications or morbidity from invasive testing as a result of screening

6. Death from invasive testing as a result of screening

7. False positives

8. Psychosocial consequences of the screening process (i.e., before or right after screening, receiving a false positive result)

9. Incidental findings

*Rated as critical outcomes; others rated as important

Timing

No limitation on the duration of follow-up, except for FPs where ≥ 12 months follow-up after the screening result is required in ≥ 80% of participants (if there is no evidence found meeting this criteria we will accept ≥ 6 months follow-up)

Longest follow-up will be used for mortality, quality of life, and overdiagnosis unless there has been substantial (> 20%) contamination by the control group receiving screening

Delivery setting

Any setting relevant to primary care

Countries rated as very high on the Human Development Index 2019 [59]

Study design & publication type

• RCTs (parallel designs using individual or cluster randomization)

• Studies using modeling or simulation, or retrospectively applying differing screening criteria

• Editorials, commentaries

• Case reports and series (i.e. all participants have the outcome)

• With the exception of overdiagnosis, for harms nonrandomized studies are also eligible. For false positives, the study must use similar selection criteria and methods of determining a positive result (e.g., diameter, volumetric) as used in an RCT. If a method used in an RCT is compared with another method in a nonrandomized study these will be considered for in KQ3. For psychosocial harms, there must be at least a within-group comparison relevant to the outcome e.g., before and after the screening test, between people with a negative vs. a positive test

Note: nonrandomized studies comparing the benefits of screening selection criteria or the nodule classification systems used in the RCTs with the use of a risk prediction model or a different nodule classification system will be considered in KQ3

Journal articles

Letters, abstracts, and grey literature (e.g., government reports, results in trial registries) if information on study design (e.g., eligibility criteria, participant characteristics, presentation of scenarios) is sufficient to assess study and results are confirmed as final (accessible online or via author contact)

Language of full text

English or French

Dates of publication

Any date