Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Aug 2012
Raising orphans: how clinical development programs of drugs for rare and common diseases are different.
We compared clinical trials described in package inserts from noncancer orphan and nonorphan drugs from 1 January 2001 to 31 December 2011. Among the 37 orphan and 58 nonorphan drugs approved by the US Food and Drug Administration (US FDA) during this period, orphans had fewer clinical trials (2.8 vs. 3.5, P < 0.05) and fewer total participants (390 vs. 2,566, P < 0.001), but proportions with randomization, blinding, and placebo-controlled clinical end points were similar, as were development times. We conclude that small studies of appropriate design can support US FDA approval of new medicines for rare diseases.
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Clin. Pharmacol. Ther. · Jul 2012
Antidepressant use and risk of out-of-hospital cardiac arrest: a nationwide case-time-control study.
Treatment with some types of antidepressants has been associated with sudden cardiac death. It is unknown whether the increased risk is due to a class effect or related to specific antidepressants within drug classes. All patients in Denmark with an out-of-hospital cardiac arrest (OHCA) were identified (2001-2007). ⋯ Tricyclic antidepressants (TCAs; odds ratio (OR) = 1.69, confidence interval (CI): 1.14-2.50) and selective serotonin reuptake inhibitors (SSRIs; OR = 1.21, CI: 1.00-1.47) were both associated with comparable increases in risk of OHCA, whereas no association was found for serotonin-norepinephrine reuptake inhibitors/noradrenergic and specific serotonergic antidepressants (SNRIs/NaSSAs; OR = 1.06, CI: 0.81-1.39). The increased risks were primarily driven by: citalopram (OR = 1.29, CI: 1.02-1.63) and nortriptyline (OR = 5.14, CI: 2.17-12.2). An association between cardiac arrest and antidepressant use could be documented in both the SSRI and TCA classes of drugs.
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Clin. Pharmacol. Ther. · Jun 2012
Review Meta AnalysisWhole-genome sequencing in personalized therapeutics.
Eleven years since the initial drafts of the human genome were published, we have begun to see the first examples of the application of whole-genome sequencing to personalized diagnosis and therapeutics. The exponential decline in sequencing costs and the constant improvement in these technologies promise to further advance the use of a patient's full genetic profile in the clinic. However, realizing the potential benefit of such sequencing will require a concerted effort by science, medicine, law, and management. In this review, we discuss current approaches to decoding the 6 billion-letter genetic code of a whole genome in a clinical context, give current examples of translating this information into therapy-guiding knowledge, and list the challenges that will need to be surmounted before these powerful data can be fully exploited to forward the goals of personalized medicine.
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Clin. Pharmacol. Ther. · Jun 2012
EditorialTranslational bioinformatics: data-driven drug discovery and development.
Internet-accessible computing power and data-sharing mandates now enable researchers to interrogate thousands of publicly available databases containing molecular, clinical, and epidemiological data. With emerging new approaches, translational bioinformatics can now provide answers to previously untouchable questions, ranging from detecting population signals of adverse drug reactions to clinical interpretation of the whole genome. There are challenges, including lack of access to some data sources and software, but there are also overwhelming doses of hopes and expectations.