Table 1.

Phases of development of early cancer detection biomarkers

PhasesPurpose
Phase 1: Preclinical exploratory studiesIdentification of potentially discriminating biomarkers.
Usually involves comparing tumor tissue with normal tissue.
Exploratory data analysis is an integral part of this phase.
Phase 2: Clinical assay development for clinical diseaseOptimization of the assay (reproducibility and specimen source) used to measure the biomarker identified in phase I.
Determination of the performance characteristics of the biomarker assay to distinguish cases from noncases.
Identification of factors that are associated with biomarker levels.
Note: The cases and controls selected for this phase should ideally be representative of population to be screened.
Phase 3: Retrospective longitudinal repository studiesDetermination of the capacity, as a function of time before clinical diagnosis, of a biomarker to detect subclinical disease, using specimens obtained prior to clinical diagnosis for cases.
Identification of covariates that can modify the abilities of the biomarker to discriminate between those with and without subclinical disease.
Selection of biomarkers or panels of biomarkers that seem to be most promising.
Establishment of the criteria for a positive screening test and the screening interval, if appropriate, to be used in phase 4.
Phase 4: Prospective screening studiesDetermination of the operating characteristics of the biomarker-based screening test to detect asymptomatic cancer at an early stage of development, a point at which initiation of treatment is more likely to result in an improved outcome.
Assessment of feasibility of a large-scale screening program and compliance.
Collection of preliminary data on the effects of screening on costs and mortality due to the cancer being screened.
Phase 5: Cancer control studiesDetermining whether screening results in a reduction in disease morbidity and mortality in large, randomized, controlled, clinical trials in target populations.
Obtaining data on cost-effectiveness of the screening program.