A Meta-analysis to Assess the FDA DAVP's TLOVR Algorithm in HIV Submissions

The first meta-analysis of pivotal HIV study results utilizing data from 1 8 clinical trials involving seven NDAs with 8,046 patients of multiple NDA submissions for the treatment of HIV infection was used to determine if we can use a simplified version of the TLOVR algorithm for accelerated approval at week 24 and possibly for traditional approval at week 48. Standardized data sets for HIV RNA viral load, demography, CD4 counts, and discontinuation were created. These raw data sets used CDISC study data tabulation model naming conventions for most of the variables. Results obtained using the TLOVR algorithm, which utilized data from every visit to consider the pattern of HIV responses, were compared to a less complicated snapshot approach that only utilized HIV RNA data at the visit of interest. Given the similarity in results between the TLOVR and snapshot approaches, it appears that correcting for intermittent spikes in HIV RNA levels with the TLOVR algorithm does not have much regulatory impact.