Drug failures

D Deficient Fluid Volume related to inadequate fluid intake, need to inotease dose of drug, failure to recognize symptoms of dehydration (diabetes insipidus)... 

Pharmacological Profiling as the Tool to Avoid Drug Failure. 117... 

Predicting Side Effects to Prevent Drug Failures.118... 

The first step to increase success in clinical development is certainly to understand the causes of drug failure. The major reasons for failures of 198 NCE in clinical development have been reported to be bioavailability (39% of failures), lack of efficacy (30%), toxicity (11%), and adverse effects (10%).51,52... 

More recent studies showed that the relative importance of major causes of drug failures in clinical trials has evolved significantly from 1991 to 2000.42 In the early 1990s, major causes of clinical attrition were poor pharmacokinetics (PK) and bioavailability which together... 

Reasons for Drug Failure in Clinical Development/Withdrawal from... 

The cost of drug development continues to spiral upward. Inflation and increased regulatory requirements, however, only account for a small portion of this increase. At this time, productivity is a major issue. A review of 198 new drug candidates that reached phase I clinical studies indicates a 60% failure rate due to poor pharmacokinetic properties or toxicity [23]. On the average, less than 2% of the drug failures could be attributed to drug interactions that resulted in adverse reactions [24], In elderly patients, however, drug interactions could contribute... 

Factors other than resistance can produce drug failure. 258... 

A critical issue is that true drug resistance among schistosomes in the field is almost always masked by an expected failure rate of 5-30%. As an illustration, consider a village in which the schistosomes have a normal susceptibility to praziquantel. Treatment might cure 85% of the infected patients (and reduce the egg burden in the other 15%). But, this could be quantified as a 15% drug failure rate. In a parallel village where 2% of the worm population is resistant to the recommended dose of prazi-... 

Whereas the drug failures in northern Senegal elicited the most focused field-based studies of... 

As has already been pointed out, this failure rate is really well within the expected cure rates for praziquantel. Using the range of an expected 70-95% cure rate mentioned above, one could expect a failure rate ranging from 0.001 % to 2.7% after three treatments, and the 1.6% failure rate reported here is squarely within that expectation. So, these failures in and of themselves are not an indication of inordinate drug failure or resistance. 

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