2. Phase I clinical testing studies a drug's safety profile with particular attention to the safe dosage range. The studies also determine how a drug is absorbed, distributed, metabolized, and excreted. They usually involve testing normal, healthy volunteers.
3. IRBs are nongovernmental organizations that review research plans and can approve, disapprove, or make changes to a proposed protocol before the drug, device, or procedure is tested in humans. They evaluate the scientific rigor of the research designs, as well as seek to minimize risk to subjects, ensure informed consent, and monitor data as they are collected to ensure continued safety.
4. Phase III trials usually involve 1,000 to 3,000 patients and are carried out at several different medical centers. The purpose of the trials is to verify the therapeutic effectiveness of the compound and to provide information about adverse side effects of long-term use by studying a larger clinical population. Phase III trials last an average of 1 to 4 years. Ninety-five percent of all the compounds that initiate Phase III trials are eventually approved.
5. Expedited review is a process whereby Phases II and III are combined to shorten the approval process for new drugs to treat serious and life-threatening diseases.
6. The priority categories for the degree of novelty of the chemical compound, in decreasing order of importance, are new molecular entity, new derivative, new formulation, new combination, already-marketed drug product, and already-marketed drug product by the same firm. The magnitude of treatment potential is graded as being important gain, modest gain, or little or no gain. Drugs also can be assigned orphan drug status, but this does not independently affect their priority.
7. The purpose of Phase IV studies is twofold. For the manufacturer, the FDA, and researchers, such studies provide information about long-term effectiveness and rare or delayed side effects, qualities that can only be assessed after use in everyday clinical practice. (Phase IV data may be used also to substantiate an application for a new clinical indication or to change the drug labeling.)
8. The official policy of most payers in the United States is to pay only for the use of the drug for the clinical indications for which it was approved by the FDA—“on-label use.” While many routine and effective uses of drugs are acknowledged to be “off-label use,” many payers are increasingly using the official FDA label contract language to deny their coverage and reimbursement.
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