Drug failure rate

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-... 

Antiseizure therapy has importance implications for women s health. The efficacy of oral contraceptives is reduced by concomitant use of antiseizure drugs (failure rate of 3.1/100 years versus 0.7/100 years in nonepileptic controls) this may relate to the increased rate of oral contraceptive metabolism caused by antiseizure drugs that induce hepatic enzymes (Table 19-2) particular caution is needed with antiseizure drugs that induce CYP3A4. 

Table 10.3 presents for each country, for the period 1994-97, the number of drug samples submitted for testing, samples tested and the failure rate in those tests. Data are available from all 10 countries on the total number of samples submitted and the number of samples tested, and these show that seven countries— Australia, Cypms, Estonia, Malaysia, the Netherlands, Venezuela and Zimbabwe — have been able to meet the demand for testing (92-100%). Uganda has a relatively low test rate of 56% for the submitted samples, followed by Cuba and Tunisia at 72% and 88%, respectively. The lack of certain equipment and materials, such as reference standards and reagents, constrains analysis in Cuba, Cyprus, Uganda and Zimbabwe. 

Each of the countries operates a quality analysis system for post-marketing control of drug quality, albeit with vast differences in capacity. Data on the outcome measure for drug quality— the number of dmg samples that failed quality tests compared with the total number of samples collected— are available in all the countries, except the Netherlands. Failure rates are high in some countries, e.g. Tunisia and Uganda. In Australia, high failure rates are found for herbal and other complementary products, compared with prescription dmgs. Empirical data on sanctions applied in such instances are not available. 

Penicillin is the drug of choice for streptococcal pharyngitis, but cephalosporins may be appropriate alternative first-line agents owing to increasing failure rates after penicillin therapy. 

These plans envision composition-of-matter patents on drug molecules for which development timelines and market potentials can be estimated. Product stories are the clearest, most rational plans because profitable sales can be projected and rNPVs calculated. On the other hand, investors usually perceive higher risks because the rNPVs tend to be dominated by single product candidates for which historical failure rates are high. Examples of product stories include Amgen s development of Epogen and Amylin s development of Symlin. 

It was also revealed that when drugs were designed as novel mechanisms of action, they incurred twice the failure rate. In cases where the objective endpoints were less definitive, there were 10% more failures. When considered together—a novel mechanism and less objective endpoints—a 70% failure rate was experienced. 

Pharmaceutical firms have to reexamine their strategies to devise means to increase their drug pipelines for continuous streams of products. The high failure rates of Investigational New Drugs during clinical trials (see Exhibit 5.8) necessitate the development of better assay systems and animal models that correlate closely with human pharmacodynamics and pharmacokinetics. The study of pharmacogenomics will be crucial to address this issue. 

From a historical point of view, the research axes of the pharmaceutical industry have shifted away from acute and more toward chronic pathology solutions. The drug discovery technologies have evolved in parallel because the cost of the research linked to the failure rate has increased with the complexity of the pathology of interest. As a consequence, in order to enhance research... 

While the issue of the ethical conduct of clinical trials in pediatric psychopharmacology is addressed comprehensively elsewhere in this book, it is important to present an FDA perspective on this important matter. It is also important to have the issue of ethics discussed in the context of the scientific needs for trials presented to the FDA in support of new drug applications. These trials must be adequate and well-controlled (U.S. Department of Health and Human Services, 2001). What this requirement essentially means is that, in order to support an efficacy claim, the trials must be interpretable and must be able to document efficacy. For treatments that are intended to improve symptoms, as is almost always the case for psychotropic drugs, placebo-controlled trials are the usual standard. This is especially true when there is a substantial failure rate in placebo-controlled trials for the drugs known to work in a particular therapeutic area, as again is the case for most psychotropic drugs. Where that is true,... 

As things stand today, there are no shortcuts in drug development, regarding neither the overall development time—typically 12-15 years—nor the early identification of dropouts. The pharmaceutical industry will continue to have to contend with failure rates and timelines to bring products to market exceeding industry standards by far. 

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... 

The number of new chemical entities (NCEs) approved by the U.S. FDA has dropped in the last decade (41) and the average success rate, from the first-in-human studies to registration, is only 11% (42). The lack of drug efficacy and safety account for around 30% of the failures in the clinic (42). Thus, the ability to determine drug safety and efficacy early in the discovery process should help in reducing the failure rate during the costly development studies, and in the end it would produce better and safer drugs (43). 

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