Table 1.

Overview of the Different Scenarios, Interpretation, and Derivable Maximum Clinical Incidence Reduction (MCLIR) Methodology Metrics

Scenario	Description	Effect of Screening	Interpretation	Derivable MCLIR Metrics
NoScreen	No screening is performed during an individual’s lifetime. Lung cancers that are diagnosed due to clinical symptoms are treated with guideline-concordant treatment with observed treatment effectiveness.	No screening is performed. All cancers in this scenario are diagnosed due to clinical symptoms and are treated with guideline-concordant treatment with observed treatment effectiveness/survival.	The NoScreen Scenario serves as a comparator to evaluate the effects of screening in the other scenarios.	None.
RealSensRealTreat	A single CT screen with realistic sensitivity estimates is performed at age 65 y. All screen-detected cancers receive guideline-concordant treatment with observed treatment effectiveness.	A proportion of the existing cancers at age 65 y will be screen detected. Both screen-detected cancers and cancers diagnosed due to clinical symptoms are treated with guideline-concordant treatment with observed treatment effectiveness/survival.	The comparison of RealSensRealTreat to NoScreen allows derivation of the model predictions for how screening reduces incidence and mortality under its baseline (realistic) assumptions.	Realistic clinical incidence reduction (RCLIR): $\mathrm{RCLIR}=(1-\frac{\sum _{A=\mathrm{age}65}^{\mathrm{age}80}\mathrm{Clinical}\mathrm{incidence}\mathrm{at}\mathrm{age}A\mathrm{in}\mathrm{RealSensRealTreat}}{\sum _{A=\mathrm{age}65}^{\mathrm{age}80}\mathrm{Clinical}\mathrm{incidence}\mathrm{at}\mathrm{age}A\mathrm{in}\mathrm{NoScreen}})*100\%$ Realistic screening-induced lung cancer mortality reduction (RMOR): $\mathrm{RMOR}=(1-\frac{\sum _{A=\mathrm{age}65}^{\mathrm{age}80}\mathrm{Lung}\mathrm{cancer}\mathrm{mortality}\mathrm{at}\mathrm{age}A\mathrm{in}\mathrm{RealSensRealTreat}}{\sum _{A=\mathrm{age}65}^{\mathrm{age}80}\mathrm{Lung}\mathrm{cancer}\mathrm{mortality}\mathrm{at}\mathrm{age}A\mathrm{in}\mathrm{NoScreen}})*100\%$
RealSensPerfectTreat	A single CT screen with realistic sensitivity estimates is performed at age 65 y. All screen-detected cancers receive perfect treatment (i.e., have a 100% lifetime survival rate).	A proportion of the existing cancers at age 65 y will be screen detected. However, all of the screen-detected cancers receive perfect treatment and will not lead to lung cancer death. Lung cancers that develop after age 65 y can be diagnosed only due to clinical symptoms and are treated with guideline-concordant treatment with observed treatment effectiveness/survival.	The comparison of RealSensRealTreat to RealSensPerfectTreat allows derivation of the potential effects of improvements in the treatment of screen-detected cases on lung cancer mortality under baseline sensitivity estimates.	Screening-induced lung cancer mortality reduction under perfect treatment but imperfect sensitivity (ISMOR): $\mathrm{ISMOR}=(1-\frac{\sum _{A=\mathrm{age}65}^{\mathrm{age}80}\mathrm{Lung}\mathrm{cancer}\mathrm{mortality}\mathrm{at}\mathrm{age}A\mathrm{in}\mathrm{RealSensPerfectTreat}}{\sum _{A=\mathrm{age}65}^{\mathrm{age}80}\mathrm{Lung}\mathrm{cancer}\mathrm{mortality}\mathrm{at}\mathrm{age}A\mathrm{in}\mathrm{NoScreen}})*100\%$
PerfectSensTreat	A single screen with perfect sensitivity (100%) is performed at age 65 y. All screen-detected cancers receive perfect treatment (i.e., have a 100% lifetime survival rate).	All existing cancers at age 65 are screen-detected. Furthermore, all of the screen-detected cancers receive perfect treatment and will not lead to lung cancer death. Lung cancers that develop after age 65 can only be diagnosed due to clinical symptoms and are treated with guideline-concordant treatment with observed treatment effectiveness/survival.	The comparison of PerfectSensTreat to NoScreen provides the maximum clinical incidence reduction (MCLIR), by removing all existing cancers through screen detection. The MCLIR thus provides an overview of the sojourn time distribution, with the time between the moment of screening and the MCLIR curve reaching 0% reflecting the maximum sojourn time. In addition, the comparison between PerfectSensTreat and NoScreen provides the maximum mortality reduction (MMOR) achievable by screening, as all cancers that exist at the moment of screening are detected and treated with perfect effectiveness. Finally, the comparison between PerfectSensTreat and RealSensPerfectTreat also provides information on the value of improvements in sensitivity on screening-induced lung cancer mortality reductions.	Maximum clinical incidence reduction (MCLIR): $\mathrm{MCLIR}=(1-\frac{\sum _{A=\mathrm{age}65}^{\mathrm{age}80}\mathrm{Clinical}\mathrm{incidence}\mathrm{at}\mathrm{age}A\mathrm{in}\mathrm{PerfectSensTreat}}{\sum _{A=\mathrm{age}65}^{\mathrm{age}80}\mathrm{Clinical}\mathrm{incidence}\mathrm{at}\mathrm{age}A\mathrm{in}\mathrm{NoScreen}})*100\%$ Screening-induced maximum lung cancer mortality reduction (MMOR): $\mathrm{MMOR}=(1-\frac{\sum _{A=\mathrm{age}65}^{\mathrm{age}80}\mathrm{Lung}\mathrm{cancer}\mathrm{mortality}\mathrm{at}\mathrm{age}A\mathrm{in}\mathrm{PerfectSensTreat}}{\sum _{A=\mathrm{age}65}^{\mathrm{age}80}\mathrm{Lung}\mathrm{cancer}\mathrm{mortality}\mathrm{at}\mathrm{age}A\mathrm{in}\mathrm{NoScreen}})*100\%$

CT, computed tomography.