TABLE 2.

Technical and analytical issues associated with different model systems for studying combination antifungal therapy

CategoryCharacteristic
In vitro studiesAnimal modelsClinical trials
StrengthsEasily repeated across a wide variety of drug concentrationsStudies can be done with homogeneous hostsThis is the answer that matters
Easily subjected to statistical testingHost factors are integrated
Easy to vary technical factorsResistant isolates can sometimes be tested
Easy to test multiple isolatesQuantitative endpoints (tissue burden, rate of clearance) can be tested
Easy to test isolates with defined types of resistanceA range of doses and dose combinations can be tested
WeaknessesRelevance of in vitro methods not always clearInfection models are often poor mimics of human diseaseSubjects and infecting isolates are heterogeneous
Host factors are ignoredPharmacokinetic and toxicological behavior of test drugs (and their pharmacological effects on each other) may not mimic that seen in humansNo ability to control nature of infecting isolate
Pharmacokinetic factors are ignoredOnly limited numbers of isolates can be testedUnderlying disease cannot be controlled
Only limited numbers of repetitions are possibleLack of quantitative endpoints for many diseases
Resistant isolates sometimes have reduced virulenceLimited ability to study a range of doses
Very expensive
Slow