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At time of writing, PharmD Student School of Pharmacy Lake Erie College of Osteopathic Medicine Erie, Pennsylvania
At time of writing, PharmD Student School of Pharmacy Lake Erie College of Osteopathic Medicine
Chair Department of Pharmacy Practice School of Pharmacy Lake Erie College of Osteopathic Medicine 1858 West Grandview Boulevard Erie, Pennsylvania 16509 fax 814/866-8450 lsasich{at}lecom.edu
Published Online, October 30, 2007. www.theannals.com, DOI 10.1345/aph.1K268
Approval packages and briefing documents may contain rigorously reviewed clinical trial reports that have not been published at the time a drug is approved or that may never be published. Inclusion of these unpublished trials in new drug reviews may impact formulary committee decisions and drug selection by clinicians for treatment of individual patients.
Approval packages and briefing documents are available on the FDA's Web site. However, that site is large and difficult to navigate, thus inhibiting the use of this information by healthcare professionals. We present the steps necessary to locate approval packages for approved drugs and briefing documents for drugs that will be or already have been reviewed by an FDA advisory committee (Table 1).
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The importance of approval packages and briefing documents can be demonstrated by examining the data submitted for telithromycin and muraglitazar. The approval package for telithromycin contains background information about the regulatory history and previous advisory committee meetings that discussed the drug. In 2001, an FDA advisory committee recommended against approval of telithromycin. This recommendation was based on concerns expressed by FDA medical officers that the drug offered no unique benefit over already approved antibiotics and because of questions of hepatotoxicity, QT interval prolongation, and debilitating vision disturbances.1 The drug's sponsor responded by conducting a large safety trial, the results of which were so questionable that the FDA would not use them. In response, the FDA requested post-marketing data from case reports from other countries rather than another clinical trial.2 The drug's original labeling lacked the necessary data and the context around the FDA's safety concerns to be of use in making formulary or prescribing decisions. The inclusion of approved package information in reviews of telithromycin could have significantly influenced the decisions of formulary committees and clinicians regarding the prescribing of this drug.
In 2005, an FDA advisory committee reviewed the safety and efficacy of muraglitazar and recommended the drug's approval; the agency issued an approvable letter.3 Nissen et al.4 reviewed and analyzed the briefing documents5 for muraglitazar and found an increased risk in the composite outcome of death and congestive heart failure in patients treated with the drug. Only 1 of 5 trials submitted to the FDA had been published at the time of the advisory committee meeting. The authors concluded that muraglitazar should not have been approved.
We suggest that it may not be possible to conduct an independent review of the therapeutic value of new drugs by relying only on peer-reviewed medical literature. FDA approval packages and briefing documents provide rigorous evaluations of both published and unpublished trials. These data may impact the perception of the therapeutic value of new pharmaceuticals.
References
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