Lessons from Large-Scale Tolerability and Acceptability Studies of Triple Drug Mass Drug Administration Performed to Support Policy Change and Accelerate Elimination of Lymphatic Filariasis.

Early clinical trials clearly demonstrated the superior efficacy of triple drug therapy with ivermectin plus DEC and albendazole (IDA) for clearing microfilaremia (Mf) in individuals with lymphatic filariasis (LF). Although these initial pharmacokinetic and efficacy studies were necessary first steps in the clinical development of IDA, they were not sufficient to justify policy changes necessary for widespread use of this new regimen by national filariasis elimination programs. Processes and procedures that led to the World Health Organization's (WHO) endorsement of IDA as a mass drug administration (MDA) regimen for LF are reviewed elsewhere in this Supplement. However, the "guideline review process" depended heavily on preliminary results from multicenter studies that were performed to compare the safety, tolerability, and acceptability of IDA versus DA (the two-drug regimen of DEC plus albendazole that was recommended for use for filariasis elimination in countries without co-endemic onchocerciasis or loiasis). Efficacy and tolerability results from those studies have been recently published. Therefore, this paper will focus on practical aspects of the planning and conduct of the large-scale studies that were so critically important for policy change.