Insufficient therapeutic index

Insufficient therapeutic index is a major cause of candidate attrition in drug development. The lack of appropriate prediction of safety liabilities results in unforeseen adverse events in clinical trials or the unwarranted abandonment of potentially safe and effective therapies. Throughout the drug discovery process, therapeutic and toxic exposures are determined, and clinical safety biomarkers are essential for... 

Batist et reported results from an early trial using Myocet for the treatment of MBC and concluded that Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and Grade 4 neutropenia and provides comparable antitnmor efficacy, when used in combination with cyclophosphamide for the first line treatment of MBC. However, these conclnsions were not accepted by FDA as they concluded that the trial had insufficient patients, hence insnfficient power, to infer this based on statistical analysis. ... 

Other inotropic drugs are necessary not to replace digitalis as much as to supplement in cases of severe heart failure refractory to the glycosides, and in situations where their efficacy is insufficient and the therapeutic index is too low. The clinical goal is to improve the symptoms of cardiac failure by improving left ventricular function or by reducing resistance to the heart s output against the peripheral circulation—or even better—to achieve both. 

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