The quandary of compounding for MCOs: administrative costs, risks, and waste.
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PURPOSE: Pharmacy compounding of prescription therapies that do not have Food and Drug Administration (FDA) approval increases administrative costs to managed care organizations and may also place members at risk for poor outcomes. This paper provides health care administrators with information and tools that can be used to manage risk-encouraged practices from pharmacy compounders, and suggests methods for evaluating the medical appropriateness and benefit of such compounds. STUDY DESIGN: Experiential findings. RESULTS: Methods indicate an effective way to manage this emerging pharmacy practice based on safety, risk avoidance, and outcomes. CONCLUSION: Focused management efforts can reduce the burden of reimbursement for compounding practices that are likely to present a greater risk of medical errors than commercially prepared medications. The use of existing terms in plan contracts, such as "experimental treatments or medications," "medical necessity," or "non-FDA approved agents," can enable an editing process that provides for appropriate benefit enforcement and control. (+info)
International Conference on Harmonisation; revised guidance on Q3A impurities in new drug substances; availability. Notice.
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The Food and Drug Administration (FDA) is announcing the availability of a revised guidance entitled "Q3A(R) Impurities in New Drug Substances." The revised guidance, which updates a guidance on the same topic published in the Federal Register of January 4, 1996 (the 1996 guidance), was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The revised guidance clarifies the 1996 guidance, adds information, and provides consistency with more recently published ICH guidances. The revised guidance is intended to provide guidance to applicants for drug marketing registration on the content and qualification of impurities in new drug substances produced by chemical syntheses and not previously registered in a country, region, or member State. (+info)
Frequency of positive studies among fixed and flexible dose antidepressant clinical trials: an analysis of the food and drug administration summary basis of approval reports.
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The assumption that the design of an antidepressant clinical trial affects the outcome of that trial is based on sparse data. We sought to examine if the dosing schedule, either a fixed dose or a flexible dose type, in an antidepressant clinical trial affects the frequency with which antidepressants show statistical superiority over placebo. Randomized, placebo-controlled clinical trials of nine antidepressants approved by the Food and Drug Administration between 1985 and 2000 were reviewed. These trials comprised 9313 depressed patients who participated in 51 antidepressant clinical trials consisting of 92 treatment arms with eventual approved doses. In the flexible dose trials, 59.6% (34/57) of the antidepressant treatment arms were statistically significant compared to placebo, whereas in the fixed dose trials only 31.4% (11/35) of the antidepressant treatment arms were statistically significant compared to placebo (chi(2)=6.9, df=1, p<0.01). These data suggest that the antidepressant dose schedule may influence trial outcome due in part to a significantly lower magnitude of symptom reduction with placebo in flexible dose trials (F=4.08, df=1, 48, p&<0.05) compared to fixed dose trials. Symptom reduction was similar with antidepressants in the flexible and fixed dose trials. Further, the primary function of finding a dose-response relationship was not found among the fixed dose studies. (+info)
Regulatory approvals of pediatric oncology drugs: previous experience and new initiatives.
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PURPOSE: To review the Food and Drug Administration (FDA) experience with approvals of new drugs for pediatric oncology and to discuss new regulatory initiatives directed at pediatric oncology. METHODS: A retrospective review of FDA archival documents and the published literature. RESULTS: More than 100 drugs have been approved by the Division of Oncology Drug Products of the FDA for the treatment of malignancies. Only 15 have pediatric use information in their labeling, which is less than 50% of the drugs commonly used in the treatment of pediatric malignancies. In the past 20 years, there have been six submissions to the FDA for pediatric oncology indications. To illustrate principles of the approval process, each submission is discussed. CONCLUSION: Potential reasons for a lack of New Drug Application submissions for pediatric oncology include the small pediatric oncology market compared with the adult oncology market and perceived barriers to performing studies in children. Reasons for failure to approve pediatric indications include small numbers of patients, lack of appropriate controls, and failure to demonstrate patient benefit. Approval criteria include the use of controlled trials, prospective data collection, and disease-appropriate end points. Regulatory initiatives to promote pediatric therapeutic development and product labeling are discussed. (+info)
Review of the newer antiepileptic drugs.
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This review article discusses the newer anti-epileptic drugs gabapentin, lamotrigine, tiagabine, topiramate, levetiracetam, oxcarbazepine, and zonisamide. Emphasis is given to FDA-approved indications and place in therapy. The mechanisms of action and pharmacokinetics of each drug is provided and the most common adverse effects are reviewed. Clinical studies leading to FDA approval are discussed. Practical points on proper dosing and monitoring are stressed, and drug interactions are also included. (+info)
End points and United States Food and Drug Administration approval of oncology drugs.
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PURPOSE: To summarize the end points used by the United States Food and Drug Administration (FDA) to approve new cancer drug applications over the last 13 years. MATERIALS AND METHODS: The FDA granted marketing approval to 71 oncology drug applications between January 1, 1990, and November 1, 2002. The end points used as the approval basis for each application are presented, and the rationale for each end point is discussed. RESULTS: The FDA grants either regular marketing approval or accelerated marketing approval for oncology drug applications. Regular approval is based on end points that demonstrate that the drug provides a longer life, a better life, or a favorable effect on an established surrogate for a longer life or a better life. Accelerated approval (AA) is based on a surrogate end point that is less well established but that is reasonably likely to predict a longer or a better life. Tumor response was the approval basis in 26 of 57 regular approvals, supported by relief of tumor-specific symptoms in nine of these 26 regular approvals. Relief of tumor-specific symptoms provided critical support for approval in 13 of 57 regular approvals. Approval was based on tumor response in 12 of 14 AAs. CONCLUSION: End points other than survival were the approval basis for 68% (39 of 57) of oncology drug marketing applications granted regular approval and for all 14 applications granted accelerated approval from January 1, 1990, to November 1, 2002. (+info)
Comparison of gallbladder function obtained with regular CCK-8 and pharmacy-compounded CCK-8.
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This study was undertaken to test whether the octapeptide of cholecystokinin (regular CCK-8) and pharmacy-compounded CCK-8 produce similar results with regard to gallbladder function. METHODS: Twenty patients with suspected gallbladder disease were enrolled into quantitative cholescintigraphy. Each patient was infused for 10 min with 3 ng/kg/min of regular CCK-8 and pharmacy-compounded CCK-8, sequentially, with a 30-min interval between the beginning of infusion. The gallbladder ejection fraction, latent period, ejection period, and ejection rate were measured with both agents. RESULTS: Both regular CCK-8 and pharmacy-compounded CCK-8 produce similar, but not identical, results with close correlation between them with reference to all of the measured functions of the gallbladder. There is neither potentiation nor inhibition of the first dose on the effects of the second dose of CCK-8. CONCLUSION: Pharmacy-compounded CCK-8 functions much similar to that of regular CCK-8 as long as an interval of at least 30 min is allowed between doses. (+info)
Clinical and outcome research in oncology. The need for integration.
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Cancer is one of the main healthcare problems in Europe. Although significant progress has recently been made, long-term survival is still disappointing for most common solid tumours. The explosion of information has strengthened the need to create and sustain coordinated interaction between technology, biology, clinical research, clinical practice and health policy. A simple process based on automatic and passive translation from bench to clinical research and eventually to the bed side is usually assumed but cannot be taken for granted. A critical role might be played by Outcome Research (OR), defined as the discipline that describes, interprets, and predicts the impact of various influences, especially interventions, on final endpoints (from survival to satisfaction with care) that matter to decision makers (from patients to society at large), with special emphasis on the use of patient-reported outcomes (PRO). Recently, under pressure from several parts of society, the FDA, recognizing the need for faster drug approval, has modified existing regulations and created new rules to allow anti-cancer drugs to be approved more quickly and, in certain but quite common circumstances, single arm trials and surrogate endpoints to be used as measures of clinical benefit. In this context, the faster approval process may lead to drugs being marketed without there being a complete picture of how effective or safe they are. The FDA move to speed up drug approval, together with the use of not fully validated surrogate endpoints, give OR the unique opportunity to help understand the value of drugs that have received accelerated approval. Despite this opportunity, OR has yet to demonstrate its role in this specific setting and provide proof of the validity, reliability and added value of its primary endpoint measures when evaluated in a broader context. The implementation of lines of OR in the development and evaluation of anti-cancer drugs hinges upon the availability of specific knowledge, methods, instruments and resources and upon their appropriate integration in the mainstream of clinical research. In the USA specific interdisciplinary projects have been launched by the NCI. In Europe there is a lack of such initiatives. The correct placement of OR in the anti-cancer drug development process will guarantee the highest possible standard of validity and reliability of OR at European level and better integration of both translational and outcome research in the mainstream of clinical research into anti-cancer drugs, thus speeding up the introduction of the results of patient-oriented translational clinical research into clinical practice. (+info)