Risk‐based selection from the general population in a screening trial: Selection criteria, recruitment and power for the Dutch‐Belgian randomised lung cancer multi‐slice CT screening trial (NELSON)

TLDR

NELSON investigates whether 16‑detector multi‑slice CT screening reduces lung cancer mortality compared to no screening. The study used a questionnaire sent to 335,441 men aged 50‑75 to assess smoking exposure, estimate lung‑cancer mortality, and select participants so that the required response rate and sample size fit available resources. Selecting current and former smokers with high smoking exposure (e.g., >15 cigarettes/day for >25 years or >10 cigarettes/day for >30 years) proved optimal, requiring 17,300–27,900 participants for 80 % power to detect a 20–25 % mortality reduction, and 15,428 participants have already been randomized, demonstrating feasibility and cost‑saving benefits.

Abstract

A method to obtain the optimal selection criteria, taking into account available resources and capacity and the impact on power, is presented for the Dutch-Belgian randomised lung cancer screening trial (NELSON). NELSON investigates whether 16-detector multi-slice computed tomography screening will decrease lung cancer mortality compared to no screening. A questionnaire was sent to 335,441 (mainly) men, aged 50-75. Smoking exposure (years smoked, cigarettes/day, years quit) was determined, and expected lung cancer mortality was estimated for different selection scenarios for the 106,931 respondents, using lung cancer mortality data by level of smoking exposure (US Cancer Prevention Study I and II). Selection criteria were chosen so that the required response among eligible subjects to reach sufficient sample size was minimised and the required sample size was within our capacity. Inviting current and former smokers (quit <or= 10 years ago) who smoked >15 cigarettes/day during >25 years or >10 cigarettes/day during >30 years was most optimal. With a power of 80%, 17,300-27,900 participants are needed to show a 20-25% lung cancer mortality reduction 10 years after randomisation. Until October 18, 2005 11,103 (first recruitment round) and 4,325 (second recruitment round) (total = 15,428) participants have been randomised. Selecting participants for lung cancer screening trials based on risk estimates is feasible and helpful to minimize sample size and costs. When pooling with Danish trial data (n = +/-4,000) NELSON is the only trial without screening in controls that is expected to have 80% power to show a lung cancer mortality reduction of at least 25% 10 years after randomisation.