An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

Abstract

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.

A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles.

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 (<i>phase I</i>), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (<i>phase II</i>). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. <i>Phase III</i> prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. <i>Phase IV</i> 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.

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.

EDRN PI Authors
  • (None specified)
Medline Author List
  • Allison J
  • Benamouzig R
  • Benton S
  • Bossuyt PMM
  • Bresalier RS
  • Caro L
  • Carvalho B
  • Chiu HM
  • Coupé VMH
  • Dekker E
  • Dolwani S
  • Fraser CG
  • Grady W
  • Guittet L
  • Gupta S
  • Halloran SP
  • Haug U
  • Hoff G
  • Itzkowitz S
  • Kortlever T
  • Koulaouzidis A
  • Ladabaum U
  • Lauby-Secretan B
  • Leja M
  • Levin B
  • Levin TR
  • Macrae F
  • Meijer GA
  • Melson J
  • O'Morain C
  • Parry S
  • Rabeneck L
  • Ransohoff DF
  • Saito H
  • Sanduleanu-Dascalescu S
  • Schoen RE
  • Selby K
  • Senore C
  • Singh H
  • Steele RJC
  • Sung JJY
  • Symonds EL
  • Sáenz R
  • Winawer SJ
  • Young GP
  • de Klaver W
  • de Klerk CM
PubMed ID
Appears In
Gut, 2023 Oct (issue 10)