Evaluating diagnostic strategies for early detection of cancer: the CanTest framework

Abstract

Background Novel diagnostic triage and testing strategies to support early detection of cancer could improve clinical outcomes. Most apparently promising diagnostic tests ultimately fail because of inadequate performance in real-world, low prevalence populations such as primary care or general community populations. They should therefore be systematically evaluated before implementation to determine whether they lead to earlier detection, are cost-effective, and improve patient safety and quality of care, while minimising over-investigation and over-diagnosis. Methods We performed a systematic scoping review of frameworks for the evaluation of tests and diagnostic approaches. Results We identified 16 frameworks: none addressed the entire continuum from test development to impact on diagnosis and patient outcomes in the intended population, nor the way in which tests may be used for triage purposes as part of a wider diagnostic strategy. Informed by these findings, we developed a new framework, the ‘CanTest Framework’, which proposes five iterative research phases forming a clear translational pathway from new test development to health system implementation and evaluation. Conclusion This framework is suitable for testing in low prevalence populations, where tests are often applied for triage testing and incorporated into a wider diagnostic strategy. It has relevance for a wide range of stakeholders including patients, policymakers, purchasers, healthcare providers and industry. Electronic supplementary material The online version of this article (10.1186/s12885-019-5746-6) contains supplementary material, which is available to authorized users.

Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review

“…Fig. 1 The CanTest Framework Reproduced with permission from [15] We included all recruitment settings, as we expected that very few studies would have been carried out in community settings.…”

“…Biomarkers such as carcinoembryonic antigen (CEA) and CA19-9 are used in clinical practice predominantly for surveillance following treatment of upper GI cancers [ 9 , 11 ]. Substantial investment has been made into developing new biomarkers for early cancer detection; most such biomarker research has been conducted in laboratory and specialist clinical settings [ 12 , 13 ], where cancer prevalence is higher compared to community settings [ 14 , 15 ].…”

“…primary care), positive predictive values are lower than in high-prevalence populations seen in specialist cancer centres. Tests evaluated in high-prevalence populations tend to have lower sensitivity and higher specificity when used in low-prevalence populations [ 15 , 16 ]. This is known as the spectrum effect or spectrum bias [ 14 , 15 ] and has crucial implications for translating results from one care setting to another.…”

“…Tests evaluated in high-prevalence populations tend to have lower sensitivity and higher specificity when used in low-prevalence populations [ 15 , 16 ]. This is known as the spectrum effect or spectrum bias [ 14 , 15 ] and has crucial implications for translating results from one care setting to another. To gain an accurate understanding of how a test will perform within a low incidence setting, it must ultimately be evaluated within that setting.…”

“…In recognition of this, the CanTest Framework has been developed, proposing a 5-phase translational pathway for diagnostic tests, from new test development to health system implementation in low-prevalence populations [ 15 ]. The framework highlights the importance of evaluating not only clinical performance but also the feasibility and acceptability of implementation, patient safety and quality of care, and cost-effectiveness in the chosen clinical setting.…”