Effect of colonoscopy screening on risks of colorectal cancer and related death: instrumental variable estimation of per-protocol effects

Background We recently reported per-protocol estimates of colonoscopy screening on colorectal cancer incidence and mortality in NordICC, a large-scale randomized trial. Our results may be affected by residual confounding due to lack of detailed information on confounders. Here, we supplement our per...

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Bibliographic Details
Published in:European journal of epidemiology Vol. 40; no. 4; pp. 419 - 425
Main Authors: Shi, Joy, Løberg, Magnus, Kalager, Mette, Wieszczy, Paulina, Pilonis, Nastazja D., Adami, Hans-Olov, Kaminski, Michal F., Bretthauer, Michael, Hernán, Miguel A.
Format: Journal Article
Language:English
Published: Dordrecht Springer Netherlands 01.04.2025
Springer Nature B.V
Subjects:
Aged
Cancer
Cardiology
Clinical outcomes
Clinical trials
Colonoscopy
Colonoscopy - statistics & numerical data
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - diagnosis
Colorectal Neoplasms - epidemiology
Colorectal Neoplasms - mortality
Colorectal Neoplasms - prevention & control
Confidence intervals
Disease prevention
Early Detection of Cancer - methods
Epidemiology
Estimates
Female
Health risks
Humans
Incidence
Infectious Diseases
Male
Mass Screening - methods
Medical screening
Medicine
Medicine & Public Health
Middle Aged
Mortality
Oncology
Public Health
Risk
Risk Factors
Screening
Instrumental variable
Screening
Per-protocol
Colonoscopy
Colorectal cancer
ISSN:0393-2990, 1573-7284, 1573-7284
Online Access:Get full text
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Summary:Background We recently reported per-protocol estimates of colonoscopy screening on colorectal cancer incidence and mortality in NordICC, a large-scale randomized trial. Our results may be affected by residual confounding due to lack of detailed information on confounders. Here, we supplement our per-protocol analyses with instrumental variable (IV) estimates whose validity relies on an alternate set of assumptions but does not depend on the availability of confounder data. Individuals in the NordICC trial were randomized at a 1:2 ratio to receive either an invitation to a one-time screening colonoscopy (the invited group) or no invitation (the usual-care group). We used IV analyses to estimate bounds and point estimates of per-protocol effects of colonoscopy screening on colorectal cancer incidence and mortality after 10 years follow-up. Analyses included 28,220 participants in the invited group and 56,365 participants in the usual-care group. Participation in screening was 42%. In IV per-protocol analyses, the 10-year risk of colorectal cancer was 1.13% (95% confidence interval [CI]: 1.04, 1.23) with usual care and, depending on the assumptions, 0.66% (95% CI: 035, 0.95) to 0.74% (95% CI: 0.57, 0.95) in screened individuals (risk ratio of 0.59 [95% CI: 0.30, 0.98] to 0.65 [95% CI: 0.48, 0.87]). The risk of colorectal cancer mortality at 10 years was 0.29% (95% CI: 0.24, 0.33) in the usual-care group and 0.20 (95% CI: 0.09, 0.73) to 0.22% (95% CI: 0.08, 0.37) in the screened group (risk ratio of 0.71 [95% CI: 0.31, 2.89] to 0.79 [95% CI: 0.24, 1.42]). IV estimation of per-protocol effects suggests that colonoscopy screening reduces colorectal cancer incidence by 35 to 41% after 10 years.
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ISSN:0393-2990
1573-7284
1573-7284
DOI:10.1007/s10654-025-01209-w