Table 4.

Root Cause Analysis

Reason	Possible magnitude of effect	Likelihood to explain discrepancy
Model was “wrong”
Use of LMEM was not appropriate	Small	Unlikely (but unknown for sure)
Allometric scaling was inappropriate	Unlikely	Unlikely
Wrong maturation factor used	Unlikely	Unlikely
Did not use all the data	Small	Unlikely
Differences in infected patients and healthy volunteers not accounted for in model	Small to Large	Possible to Likely
Study results were higher than normal
Racial differences (Western vs. African, Caucasians vs Blacks)	Small	Unlikely
Weight differences	Small	Unlikely
Healthy volunteers vs infected patients	High	Likely
Differences in meal types	High	Likely
Differences in stomach pH between Western and African patients	Small	Possible
Extrahepatic metabolic pathway in adults not seen in children	Small to moderate	Unlikely
Crushing of tablets in Swiss TPH study	Small	Possible
Differences in oral bioavailability between adults and children	Small	Possible
Differences in analytical methods	Small	Unlikely
Number of tablets administered	Small	Unlikely
Differences in PZQ saturation in GI tract between adults and children	Small	Unlikely