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Abstract
Background and Objectives: Excellent recommendations exist for studying therapeutic and diagnostic questions. However, we observed that good guidelines on assessment of evidence for screening questions are currently lacking. Guidelines for diagnostic research (STARD) are not pertinent in situations of screening for a disease that is currently not yet present. Conceptual model: A five-step framework (Pepe, JNCI 2001) is proposed for assessing the potential use of a biomarker as a screening tool for cervical cancer: 1) correlation studies establishing a trend between strength of expressing and severity of neoplasia; 2) diagnostic study in a clinical setting where all women are submitted to verification by the reference standard; 3) biobank-based study with assessment in archived cytology samples of the biomarker in cervical cancer cases and controls; 4) prospective cohort study with baseline assessment of the biomarker and monitoring of disease; and 5) randomised intervention study aiming to observe less severe dysplasia in the experimental arm at subsequent screening rounds. Conclusions: The five-phases framework should guide researchers and test developers in planning assessment of new biomarkers and protect clinicians and stakeholders against premature claims for insufficiently evaluated products.