TY - JOUR
T1 - An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer
T2 - the guiding principles
AU - Bresalier, Robert S.
AU - Senore, Carlo
AU - Young, Graeme P.
AU - Allison, James
AU - Benamouzig, Robert
AU - Benton, Sally
AU - Bossuyt, Patrick M. M.
AU - Caro, Luis
AU - Carvalho, Beatriz
AU - Chiu, Han-Mo
AU - Coupé, Veerle M. H.
AU - de Klaver, Willemijn
AU - de Klerk, Clasine Maria
AU - Dekker, Evelien
AU - Dolwani, Sunil
AU - Fraser, Callum G.
AU - Grady, William
AU - Guittet, Lydia
AU - Gupta, Samir
AU - Halloran, Stephen P.
AU - Haug, Ulrike
AU - Hoff, Geir
AU - Itzkowitz, Steven
AU - Kortlever, Tim
AU - Koulaouzidis, Anastasios
AU - Ladabaum, Uri
AU - Lauby-Secretan, Beatrice
AU - Leja, Marcis
AU - Levin, Bernard
AU - Levin, Theodore Robert
AU - Macrae, Finlay
AU - Meijer, Gerrit A.
AU - Melson, Joshua
AU - O'Morain, Colm
AU - Parry, Susan
AU - Rabeneck, Linda
AU - Ransohoff, David F.
AU - Sáenz, Roque
AU - Saito, Hiroshi
AU - Sanduleanu-Dascalescu, Silvia
AU - Schoen, Robert E.
AU - Selby, Kevin
AU - Singh, Harminder
AU - Steele, Robert J. C.
AU - Sung, Joseph J. Y.
AU - Symonds, Erin Leigh
AU - Winawer, Sidney J.
N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Objective: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. Design: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. Results: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. Conclusion: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.
AB - Objective: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. Design: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. Results: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. Conclusion: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.
KW - colorectal adenomas
KW - colorectal cancer
KW - colorectal cancer screening
UR - http://www.scopus.com/inward/record.url?scp=85166413371&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/gutjnl-2023-329701
DO - https://doi.org/10.1136/gutjnl-2023-329701
M3 - Article
C2 - 37463757
SN - 0017-5749
VL - 72
SP - 1904
EP - 1918
JO - Gut
JF - Gut
IS - 10
M1 - 329701
ER -