Therapeutic Failure

Therapeutic failure has been defined as a failure to accomplish the goals of treatment resulting from inadequate or inappropriate drug therapy and not related to the natural progression of disease. A lack of therapeutic effect from inadequate drug therapy may include noncompliance, recent dose reduction or discontinuation, drug–drug interaction, too low a dose of drug prescribed, and inadequate therapeutic drug monitoring.

Therapeutic failure is an important problem because of its clinical significance and its impact on the use of health care resources. As a group, older adults consume more prescription and nonprescription medications than does the rest of the population. The risks associated with high levels of medication use include therapeutic failure, medical noncompliance, and adverse drug reactions. Elderly patients on inadequate drug therapy may suffer from serious morbidity or mortality. These adverse clinical events may result in emergency department visits and hospitalization. Therapeutic failure is a costly problem estimated at billions of dollars.

Investigators have reported that the prevalence of therapeutic failure in consecutive hospitalizations for any reason ranged from 2.7% to 11.4%, whereas the prevalence of therapeutic failure in hospital admissions due only to drug-related problems ranged from 42% to 55%. Among drug-related hospital admissions of patients presenting to emergency rooms, therapeutic failure has been reported to be as high as 55.6%.

Few studies have systematically explored the effectiveness of interventions designed to reduce therapeutic failure. One study analyzed the effect of an educational intervention in a department of internal medicine on drug-related hospital admissions and found a nonsignificant decrease in admissions. Investigators have suggested implementing more intensive monitoring of patients, promoting appropriate prescribing through education and quality improvement efforts, and improving patient understanding of prescription drugs and their use. No randomized clinical trials have addressed the efficacy of any of those proposed intervention strategies, either alone or in combination.

Standardizing the definition of therapeutic failure and adopting a valid reliable instrument of measurement would be desirable and helpful in determining the incidence and risk factors of therapeutic failure and in designing effective interventions. One group of investigators recently designed and tested a new instrument for therapeutic failure. Large prospective [Page 562]studies could be useful in clarifying epidemiological issues, and multicenter randomized clinical trials could also identify which interventions would be most effective in reducing therapeutic failure and its associated costs.