Comparing the Performance of Cluster Random Sampling and Integrated Threshold Mapping for Targeting Trachoma Control, Using Computer Simulation

Background: Implementation of trachoma control strategies requires reliable district-level estimates of trachomatous inflammation–follicular (TF), generally collected using the recommended gold-standard cluster randomized surveys (CRS). Integrated Threshold Mapping (ITM) has been proposed as an integrated and cost-effective means of rapidly surveying trachoma in order to classify districts according to treatment thresholds. ITM differs from CRS in a number of important ways, including the use of a school-based sampling platform for children aged 1–9 and a different age distribution of participants. This study uses computerised sampling simulations to compare the performance of these survey designs and evaluate the impact of varying key parameters. Methodology/Principal Findings: Realistic pseudo gold standard data for 100 districts were generated that maintained the relative risk of disease between important sub-groups and incorporated empirical estimates of disease clustering at the household, village and district level. To simulate the different sampling approaches, 20 clusters were selected from each district, with individuals sampled according to the protocol for ITM and CRS. Results showed that ITM generally under-estimated the true prevalence of TF over a range of epidemiological settings and introduced more district misclassification according to treatment thresholds than did CRS. However, the extent of underestimation and resulting misclassification was found to be dependent on three main factors: (i) the district prevalence of TF; (ii) the relative risk of TF between enrolled and non-enrolled children within clusters; and (iii) the enrollment rate in schools. Conclusions/Significance: Although in some contexts the two methodologies may be equivalent, ITM can introduce a bias-dependent shift as prevalence of TF increases, resulting in a greater risk of misclassification around treatment thresholds. In addition to strengthening the evidence base around choice of trachoma survey methodologies, this study illustrates the use of a simulated approach in addressing operational research questions for trachoma but also other NTDs. Author Summary: Reliable district-level prevalence estimates of active trachoma are essential to targeting control interventions. While cluster randomised surveys (CRS) remain the recommended strategy for obtaining these estimates, more rapid and cost-effective methods that can be integrated with other diseases are under investigation. One proposed method is Integrated Threshold Mapping (ITM), which incorporates a school-based platform into the sampling protocol. This study uses a computerised sampling approach to evaluate whether ITM and CRS are equivalent, and explore the impact of varying key parameters on the performance of these sampling methodologies. The results from these simulations reflect a known limitation of school-based sampling: that resulting prevalence estimates are unreliable when the enrollment is low and/or the risk of disease in schools differs from communities. However, quantification of the performance of ITM at the district level highlights the variation in performance in different contexts and provides important information for national control programmes. The results from this study strengthen the evidence base around trachoma sampling methodologies and demonstrate the advantages of using a simulated approach to evaluate different sampling scenarios.