Type I and type II errors

Improving the Efficiency of Computed Tomography Lung Cancer Screening.

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Restricting screening to highest-risk smokers would retain most of the benefit.
In the randomized National Lung Screening Trial (NLST), three annual screenings with low-dose computed tomography (CT) lowered lung cancer–related mortality among current or former (within 15 years) smokers (age range, 55–74) with smoking histories of ≥30 pack-years (NEJM JW Gen Med Jul 14 2011). But the relatively small absolute benefit (3 fewer deaths per 1000 screened during average follow-up of 6.5 years) and the high rate of false-positive CT findings raise this question: Can we target screening to a subgroup of smokers most likely to benefit?

To address this question, researchers used data from the NLST control group to develop a risk-prediction model for lung cancer–related death; the model incorporated age, sex, race, family history, details of smoking history (i.e., pack-years, time since smoking cessation), and known pulmonary disease. Next, the researchers used the model to divide NLST participants into quintiles of 5-year risk for lung cancer–related death, which ranged from <0.5% in the first quintile to >2.0% in the fifth quintile.

The number of lung cancer deaths prevented by CT screening ranged from 1 per 5300 (in the lowest-risk quintile) to 33 per 5300 (in the highest-risk quintile). Thus, the number needed to screen to prevent 1 death ranged from 5300 in the lowest-risk quintile to 161 in the highest-risk quintile. Rates of false-positive scans were high in all quintiles (between 30% and 40%).

COMMENT

This is an important analysis. It shows that, by refining the eligibility criteria for CT screening, we could retain nearly all the benefits while lowering the number of people screened, costs, and burdens of false-positive scans.

Source: NEJM

Targeting of Low-Dose CT Screening According to the Risk of Lung-Cancer Death.

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BACKGROUND

In the National Lung Screening Trial (NLST), screening with low-dose computed tomography (CT) resulted in a 20% reduction in lung-cancer mortality among participants between the ages of 55 and 74 years with a minimum of 30 pack-years of smoking and no more than 15 years since quitting. It is not known whether the benefits and potential harms of such screening vary according to lung-cancer risk.

METHODS

We assessed the variation in efficacy, the number of false positive results, and the number of lung-cancer deaths prevented among 26,604 participants in the NLST who underwent low-dose CT screening, as compared with the 26,554 participants who underwent chest radiography, according to the quintile of 5-year risk of lung-cancer death (ranging from 0.15 to 0.55% in the lowest-risk group [quintile 1] to more than 2.00% in the highest-risk group [quintile 5]).

RESULTS

The number of lung-cancer deaths per 10,000 person-years that were prevented in the CT-screening group, as compared with the radiography group, increased according to risk quintile (0.2 in quintile 1, 3.5 in quintile 2, 5.1 in quintile 3, 11.0 in quintile 4, and 12.0 in quintile 5; P=0.01 for trend). Across risk quintiles, there were significant decreasing trends in the number of participants with false positive results per screening-prevented lung-cancer death (1648 in quintile 1, 181 in quintile 2, 147 in quintile 3, 64 in quintile 4, and 65 in quintile 5). The 60% of participants at highest risk for lung-cancer death (quintiles 3 through 5) accounted for 88% of the screening-prevented lung-cancer deaths and for 64% of participants with false positive results. The 20% of participants at lowest risk (quintile 1) accounted for only 1% of prevented lung-cancer deaths.

CONCLUSIONS

Screening with low-dose CT prevented the greatest number of deaths from lung cancer among participants who were at highest risk and prevented very few deaths among those at lowest risk. These findings provide empirical support for risk-based targeting of smokers for such screening.

Source: NEJM