Estimation of disease prevalence, true positive rate, and false positive rate of two screening tests when disease verification is applied on only screen-positives: A hierarchical model using multi-center data

Objectives: A model is proposed to estimate and compare cervical cancer screening test properties for third world populations when only subjects with a positive screen receive the gold standard test. Two fallible screening tests are compared, VIA and VILI. Methods: We extend the model of Berry et al. [1] to the multi-site case in order to pool information across sites and form better estimates for prevalences of cervical cancer, the true positive rates (TPRs), and false positive rates (FPRs). For 10 centers in five African countries and India involving more than 52,000 women, Bayesian methods were applied when gold standard results for subjects who screened negative on both tests were treated as missing. The Bayesian methods employed suitably correct for the missing screen negative subjects. The study included gold standard verification for all cases, making it possible to validate model-based estimation of accuracy using only outcomes of women with positive VIA or VILI result (ignoring verification of double negative screening test results) with the observed full data outcomes. Results: Across the sites, estimates for the sensitivity of VIA ranged from 0.792 to 0.917 while for VILI sensitivities ranged from 0.929 to 0.977. False positive estimates ranged from 0.056 to 0.256 for VIA and 0.085 to 0.269 for VILI. The pooled estimates for the TPR of VIA and VILI are 0.871 and 0.968, respectively, compared to the full data values of 0.816 and 0.918. Similarly, the pooled estimates for the FPR of VIA and VILI are 0.134 and 0.146, respectively, compared to the full data values of 0.144 and 0.146. Globally, we found VILI had a statistically significant higher sensitivity but no statistical difference for the false positive rates could be determined. Conclusion: Hierarchical Bayesian methods provide a straight forward approach to estimate screening test properties, prevalences, and to perform comparisons for screening studies where screen negative subjects do not receive the gold standard test. The hierarchical model with random effects used to analyze the sites simultaneously resulted in improved estimates compared to the single-site analyses with improved TPR estimates and nearly identical FPR estimates to the full data outcomes. Furthermore, higher TPRs but similar FPRs were observed for VILI compared to VIA.