Drug failure statistics

Provide a statement describing the total number of patients expected to complete the study this number can include an estimate of treatment failures but should not include administrative dropouts. (If patients are transferred from inpatient clinics, if they relocate, or if they do not complete the study for any other reason [not drug related], they should not be included in the total.) Establish the number of patients that must complete the study and be part of the final statistical analysis. Additional patients should always be enrolled in a clinical study to make certain that, minus study dropouts, the required number of patients needed for meaningful statistical analyses are still available, and that administrative dropouts will not jeopardize numbers needed for the final statistical analysis. 

Felbamate. Felbamate is an adjuvant anticonvulsant, containing the warning that its use is associated with a marked increase in the incidence of aplastic anemia and that patients being started on the drug should have liver function tests performed before therapy is initiated. Animal studies have revealed a statistically significant increase in hepatic cell adenomas in high dose studies (18). It is postulated that this cancer was induced by toxic by-products urethane and methyl carbamate. Felbamate is not recommended as first-line therapy and is indicated for those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia or liver failure is deemed acceptable in light of the benefits provided by its use. 

A clear understanding of the required sample size is particularly critical for Phase III trials, due to the requirement for the establishment of statistical significance in the final analyses of Phase III trials to support a submission for marketing approval. Even if a new drug seems to show evidence of clinical efficacy, without a statistically significant result the trial will normally not be accepted as pivotal evidence in support of an approval. Insufficient sample size is one of the leading causes of Phase III trial failures for drugs that otherwise appear to have adequate safety and efficacy for approval. 

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