Consensus framework for developing a target product profile of real-time PCR in Chagas disease therapeutic monitoring.

Chagas disease remains a neglected global health problem with major diagnostic and therapeutic challenges. Progression from acute to chronic infection may lead to cardiac or digestive complications in approximately 20-40% of patients, depending on geographic region and duration of follow-up. However, reliable prognostic markers are still lacking, underscoring the importance of early diagnosis and timely treatment. For over 40 years, therapy has relied on benznidazole and nifurtimox, effective in acute but inconsistent in chronic disease, with frequent adverse effects undermining adherence. Current research is testing shorter regimens, lower doses, and novel compounds. Their evaluation is constrained by the lack of standardized biomarkers of treatment response. Serology requires decades to confirm treatment effect, whereas quantitative PCR (qPCR) enables earlier detection of therapeutic failure. However, heterogeneity of qPCR protocols hampers cross-trial comparisons and meta-analyses. To resolve these limitations, the Drugs for Neglected Diseases initiative convened experts to build consensus on qPCR application in clinical trials aiming to define a target product profile supporting drug development and regulatory approval.