Aug. 14, 2002 Washington, DC -- More than 20% of the drugs approved in the United States are approved at a dosage level that is later discovered to be too high, resulting in the subsequent lowering of the recommended dosage level, according to research conducted at Georgetown University's Center for Drug Development Science (CDDS). Two papers on this subject have been published in the August issue of the British journal Pharmacoepidemiology and Drug Safety. These dosage changes reveal a discrepancy between the dosage information gathered from pre-marketing studies and that needed for safe and effective use in clinical practice. Avoiding needless overdosing could reduce both side effects and costs of prescription drugs.
In the modern drug development process, great pressure is placed on defining a drug dosage early in the clinical evaluation stage, when information about the drug and its actions is sparse. Ideally, this dosage should remain the same throughout the lifetime of the drug, but the studies published this week indicate that the dosages of cardiovascular and most other classes of drugs are initially overestimated. These overestimated doses are discovered at various times after the drug is introduced into medical practice.
The Georgetown researchers studied the label changes made for all the new drugs approved for use in the United States by the FDA between 1980 and 1999. The team was led by James Cross, MS, regulatory project manager in the FDA's Center for Drug Evaluation and Research (CDER), who was a CDDS research fellow when the research was conducted. They found that dosage changes occurred in 21% of the drugs. Of these, 79% were due to safety concerns. "This pattern may represent a systematic flaw in pre-marketing dosage evaluation," the authors said.
In a separate paper, Dutch researchers from Utrecht University and Maastricht University, observed a similar proportion of dosage changes in drugs introduced in other countries, with the exception of antibiotics, which, according to the data, tend to need increasing doses after market introduction.
Both papers offer several possible reasons for these changes. These include lower doses being tested and found to be as effective subsequent to the drug's approval, changes in regulatory practice, and misjudgements made in the early phases of new drug development. All the researchers agree that further study on the process of dose-selection is needed to ensure that patients get the optimal dose right from the start.
The mission of Georgetown's Center For Drug Development Science is to establish clinical drug development science as a rigorous academic discipline for advancing new scientific methodologies, to contribute to the education of scientists engaged in clinical evaluation of drugs, and to provide solutions to real-world drug development problems. For more information, visit http://cdds.georgetown.edu.
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